IOTIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1 Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Biotin: 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: 0-597-84355-4 1. Biotin-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
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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 biotin. 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 BIOTIN ....................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Biotin............................................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 75 CHAPTER 2. NUTRITION AND BIOTIN ............................................................................................. 99 Overview...................................................................................................................................... 99 Finding Nutrition Studies on Biotin ........................................................................................... 99 Federal Resources on Nutrition ................................................................................................. 104 Additional Web Resources ......................................................................................................... 104 CHAPTER 3. ALTERNATIVE MEDICINE AND BIOTIN ..................................................................... 107 Overview.................................................................................................................................... 107 National Center for Complementary and Alternative Medicine................................................ 107 Additional Web Resources ......................................................................................................... 122 General References ..................................................................................................................... 125 CHAPTER 4. DISSERTATIONS ON BIOTIN ....................................................................................... 127 Overview.................................................................................................................................... 127 Dissertations on Biotin .............................................................................................................. 127 Keeping Current ........................................................................................................................ 128 CHAPTER 5. PATENTS ON BIOTIN.................................................................................................. 129 Overview.................................................................................................................................... 129 Patents on Biotin........................................................................................................................ 129 Patent Applications on Biotin.................................................................................................... 160 Keeping Current ........................................................................................................................ 195 CHAPTER 6. BOOKS ON BIOTIN ..................................................................................................... 197 Overview.................................................................................................................................... 197 Book Summaries: Federal Agencies............................................................................................ 197 Book Summaries: Online Booksellers......................................................................................... 198 Chapters on Biotin ..................................................................................................................... 198 CHAPTER 7. PERIODICALS AND NEWS ON BIOTIN ....................................................................... 201 Overview.................................................................................................................................... 201 News Services and Press Releases.............................................................................................. 201 Academic Periodicals covering Biotin........................................................................................ 202 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 207 Overview.................................................................................................................................... 207 NIH Guidelines.......................................................................................................................... 207 NIH Databases........................................................................................................................... 209 Other Commercial Databases..................................................................................................... 211 The Genome Project and Biotin ................................................................................................. 211 APPENDIX B. PATIENT RESOURCES ............................................................................................... 215 Overview.................................................................................................................................... 215 Patient Guideline Sources.......................................................................................................... 215 Finding Associations.................................................................................................................. 217 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 219 Overview.................................................................................................................................... 219 Preparation................................................................................................................................. 219 Finding a Local Medical Library................................................................................................ 219 Medical Libraries in the U.S. and Canada ................................................................................. 219
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ONLINE GLOSSARIES................................................................................................................ 225 Online Dictionary Directories ................................................................................................... 225 BIOTIN DICTIONARY ................................................................................................................ 227 INDEX .............................................................................................................................................. 319
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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 biotin is indexed in search engines, such as www.google.com or others, a nonsystematic 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 biotin, 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 biotin, 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 biotin. 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 biotin, 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 biotin. 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 BIOTIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on biotin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and biotin, 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 “biotin” (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: •
Comparison of the Nutritional Composition of Diets of Persons with Fecal Incontinence and That of Age-and Gender-Matched Controls Source: Journal of WOCN. Journal of Wound, Ostomy and Continence Nurses. 27(2): 9097. March 2000. Contact: Available from Journal of WOCN, Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 453-4351. Summary: In clinical and research experience, persons with fecal incontinence (involuntary loss of stool) anecdotally report altered diet intake to avoid incontinence. This article reports on a study undertaken to compare the dietary intake of 39 persons with fecal incontinence living in the community with that of age and gender matched control subjects who had normal bowel function. The diets of both groups were
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compared with recommended dietary allowances (RDAs) for their constituent nutrients. Subjects prospectively recorded the type, amount, and method of preparing all foods and beverages ingested for 8 consecutive days; diet records were analyzed using a nutrition software program. There were no significant differences in the intake of total kilocalories, protein, fat, dietary fiber, caffeine, or lactose by the fecal incontinence and control groups. The fecal incontinence group had a greater intake of carbohydrates, manganese, and vitamin B1 compared with the control group. Diets of both groups exceeded 100 percent of the RDA for protein, phosphorus, iron, sodium, potassium, Vitamins B1, B2, B3, B12 and C, and folate. Diets of both groups had less than 50 percent of the RDA for biotin, chromium, copper, and manganese but did not differ significantly. The authors conclude that the diets of persons with fecal incontinence were similar to those of control subjects with normal bowel function. Both the fecal incontinence and control groups may improve their nutritional patterns by lowering sodium and protein intake and increasing dietary fiber and monounsaturated fat intake. Calcium and vitamin D supplementation may improve dietary deficiencies and lower disease risks. Including a nutritional assessment and consultation in the care of persons with fecal incontinence to improve their general health and prevent disease is recommended, but consideration must be given to altered diet patterns perceived by the patient to prevent fecal incontinence. 4 tables. 36 references. •
Water-Soluble Vitamin Status in Patients With Renal Disease Treated With Hemodialysis or Peritoneal Dialysis Source: Journal of Renal Nutrition. 1(2): 56-73. April 1991. Summary: Patients with end-stage renal disease (ESRD) who are receiving some mode of dialysis treatment comprise a subset of the population for whom water-soluble vitamin therapy may be indicated. This article examines this population and the uses of vitamin therapy. Factors that contribute to a need for vitamin supplementation include limitations to the intake of a well-balanced diet, metabolic derangements due to uremia and associated syndromes, drug interference with absorption and/or action of specific vitamins, changed requirements in the aged population, and the process of dialysis itself. The author reviews the literature in this area and suggests that daily replacement with the US Recommended Daily Allowance is indicated for B1, B2, B12, niacin or niacinamide, pantothenic acid, and biotin. 3 figures. 4 tables. 63 references. (AA-M).
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Treat Your Nails With Kid Gloves Source: Healthy Skin and Hair. p. 6-7. Winter 2001. Contact: Available from Quadrant HealthCom, Inc. 26 Main Street, Chatham, NJ 079282402. (973) 701-8900. Fax: (973) 701-8892. Summary: This journal article discusses how the health of the nails reflects the overall health of the body and provides tips for keeping nails healthy. Fingernails and toenails are made up of protein layers called keratin. Nails grow quickly in children. Aging and menopause slow nail growth and tend to make nails thicker and brittle. Splitting, peeling, or chipping of nails may indicate a vitamin or mineral deficiency. Ridges, white spots, and spooning can indicate severe illness, thyroid disorder or fungus, and iron deficiency, respectively. Dry and peeling nails may be due to nutritional deficiencies brought on by starvation and yo-yo diets. To keep the nails healthy, they should be kept clean and in dry weather soaked in warm water and then rubbed in a cream or emollient. Gloves should be worn when using detergents or chemical solvents. Onychomycosis, a fungal infection occurring more frequently in older people and
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patients with diabetes, should be treated with topical and oral medications. Older patients should take a multivitamin plus biotin and vitamin A. •
Synovial Membrane Inflammation and Cytokine Production in Patients With Early Osteoarthritis Source: Journal of Rheumatology. 24(2):365-371; 1997. Summary: This journal article for health professionals describes a study that examined synovial membrane histopathology and cytokine content at various stages in the development of osteoarthritis (OA). Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables, including thickness of lining layer, vascularity, and inflammatory cell infiltrate, were by a blinded observer. In a subset of 20 patients, production of interleukin 1alpha (IL1alpha), interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled riboprobes and immunohistochemistry. Results show that there was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA. The most marked changes were seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1alpha, IL-1beta, and TNF-alpha was present in synovial membranes from all patients with OA, regardless of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of Il-1ra to IL-1alpha and beta with increasing grades of OA. Results suggest that significant inflammation occurs in the synovial membrane that may contribute to the continued damage of articular cartilage as a result of cytokine production. 24 references, 4 figures, and 2 tables. (AA-M).
Federally Funded Research on Biotin The U.S. Government supports a variety of research studies relating to biotin. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to biotin. 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 biotin. The following is typical of the type of information found when searching the CRISP database for biotin:
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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Project Title: A NEW HEPATOCYTE-SPECIFIC LIGAND FOR GENE DELIVERY Principal Investigator & Institution: Wong, So M.; Mirus Corporation 505 S Rosa Rd, #104 Madison, Wi 53711 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): We have recently identified a protein, the T7 phage tail fiber protein (p17), which initiated the rapid and selective uptake of the intact T7 phage head, a 60 nm DNA containing icosahedral protein shell, by mouse hepatocytes in vivo. We mapped the hepatocyte-targeting function to the central part of the protein a triple helix forming rod domain. Both the full-length p17 and rod domain alone were able to initiate the accumulation of various protein fusion partners into hepatocytes in vivo. We postulate that this protein will be a powerful new targeting signal for liver gene delivery. The overall goal for this phase I proposal is to determine if the highly efficient p17 mediated hepatocyte targeting of the relatively large T7 phage can be capitalized for hepatocyte specific delivery of heterologous DNA particles. In order to evaluate the potential of pl 7 as a targeting ligand, the first technical hurdle is to develop linkage technology for attaching p17 to DNA particles so that the function of the protein is also preserved. Once a functional attachment method is developed the utility to deliver Virus' proprietary DNA particles systems will be assessed. Successful outcome of this proposal will form basis for further development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A NEW PEPTIDE LIGAND FOR TARGETING HEPATOCYTES IN VIVO Principal Investigator & Institution: Wolff, Jon A.; Professor; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Hepatocytes are an important target for the delivery of pharmacological agents. Greater efficacy and decreased toxicity would be gained by delivering these therapeutic agents, small and large, more selectively to hepatocytes. Our preliminary results describe the discovery of a new protein determinant, within the p17 protein of T7 phage that enables the highly efficient delivery of fusion proteins and phage particles to hepatocytes in mice in vivo. Our hypothesis is that this ligand is a promising ligand for delivery of both particulate and soluble agents into hepatocytes in vivo because it interacts with a hepatocyte-specific receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ABC-TRANSPORTER BINDING PROTEINS AND TRAFFICKING Principal Investigator & Institution: Ortiz, Daniel F.; Physiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The ABC (ATP-Binding-Cassette)-type proteins SPGP and MDR3 are essential for bile formation. SPGP mediates ATP-dependent transport of conjugated bile acids across the canalicular membrane and MDR3 is a phospholipid flippase that mediates transfer of phosphatidylcholine to bile. The transporters, which reside primarily in the canalicular membrane, can be recruited or removed from the apical domain in response to signals such as bile acids, cAMP or changes in osmolarity. Mobilization and targeting of the transporters to and from the canalicular membrane is probably mediated by association with proteins that link SPGP
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and MDR3 to sorting and trafficking networks. However, outside of the interaction between CFTR and NHERF, which is essential for polarized sorting of the chloride channel, little is known about proteins that bind and regulate trafficking of ABCtransporters. We have identified two proteins that specifically bind MDR3 and SPGP. GST-pulldowns from liver homogenates, FRET analyses and co-immunoprecipitation of transporters with associated proteins, confirmed the validity of these interactions. The goal of the proposed research is to study the role of these binding proteins in regulation of SPGP trafficking in polarized cells. Experiments in Aim 1 will use immunofluorescence microscopy and FRET to establish the sites in hepatocytes where SPGP interacts with binding partners, and the effect of stimuli which induce SPGP recruitment to, or retrieval from, the canalicular membrane. Aim 2 focuses on determining the function of the interacting proteins vis-a-vis SPGP trafficking. The specific amino acid motifs in SPGP which mediate its association with interacting proteins will be identified using yeast two hybrid assays. These moieties will be mutated with the objective of generating mutant transporters that do not bind interacting proteins. Trafficking of the SPGP mutants will be studied in polarized cell model systems to determine the function of the association with the interacting proteins. Mutations which cause abnormal trafficking of canalicular ABC-transporters have been associated with cholestasis of pregnancy and Dubin-Johnson syndrome. Therefore, elucidating the pathways that govern transfer and recruitment of ABC-transporters to the apical membrane, and identifying proteins which control these processes, will provide critical insight into mechanisms underlying cholestasis and suggest targets for therapeutic drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMINOGLYCOSIDE ANTIVIRALS TO COMBAT ARENAVIRUSES Principal Investigator & Institution: De La Torre, Juan C.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an excellent model to study the molecular and cellular biology of arenaviruses that cause important and severe human diseases like Lassa fever virus (LFV) and the South American viral hemorrhagic fevers (SAHF). In addition, weaponized forms of these viruses pose a real threat as agents of bioterrorism. No licensed vaccine is available in the US, and currently there is not efficacious therapy to treat these viral infections. Therefore the importance of developing novel effective antiviral drugs to combat pathogenic arenaviruses. We have developed a reverse genetic system for LCMV. This system provides us with a robust platform for the development of novel strategies to target specific steps of the Arenavirus life cycle. We have molecularly characterized the Arenavirus genome promoter. Disruption of the interaction between the viral polymerase and promoter is predicted to abrogate virus multiplication. RNA molecules can form intricate structures that can be targeted by selected specific high-affinity antagonists. This proposal will explore the use of aminoglycoside-based small molecules to target and functionally disrupt the Arenavirus genome promoter, thus inhibiting virus infection. Aim 1 is the screening of combinatorial aminoglycoside libraries to identify small molecules that bind to the LCMV genome promoter. For this, biotin-RNA conjugates of the LCMV promoter will be attached to streptavidin-coated sensor chips and used as a ligand to screen the libraries using surface plasmon resonance. Aim 2 will assess the antiviral activity of binder molecules (Aim 1). Selected aminoglycosides will be tested for: (i) their effects on
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RNA synthesis mediated by the LCMV polymerase using our LCMV minigenome system; (ii) their ability to inhibit LCMV multiplication in cultured cells. Finlly, Aim 3 will assess the generation of viral variants resistant to antiviral aminoglycosides. Emergence of resistant variants will be assessed based on production of infectious virus and intracellular levels of virus RNA synthesis during serial passages in the presence of aminoglycosides with anti-LCMV activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS TO ENHANCE SENSITIVITY FOR MEMBRANE PROTEINS Principal Investigator & Institution: Hanash, Samir M.; Professor and Director; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) For quite some time, the standard approach for comprehensive profiling of protein expression in tissues an cell populations has been two-dimensional (2-D) gel electrophoresis and silver staining, coupled more recently with mass spectrometry for protein identification. This approach is currently in use in the PI's laboratory, fo NCI funded projects whose objectives are the molecular analysis of tumors to devise novel classification schemes of cancer, and the identification of novel protein markers for early cancer diagnosis. The standard 2- approach generally allows detection of 1000-2000 protein isoforms in a tissue sample, which is far short of the number of protein isoforms contained in a cell or tissue type. In particular, the 2-D analysis of whole cell lysates yields few proteins from cellular compartments such as membrane proteins. The tagging of proteins b, biotinylation has been extensively utilized for the selective capture and analysis of individual proteins an. antigens and has the potential for providing a substantial increment in sensitivity for the analysis of whole subsets of proteins. Preliminary data obtained by the applicant group demonstrate a remarkable increase in sensitivity and in the yield of low abundance membrane proteins using this approach. The objectives of this application are to develop procedures for the systematic separation, quantitative analysis, identification anc databasing of biotinylated membrane proteins from cells and tissues, that take advantage of the increased sensitivity of this approach. The goals of the R21 phase are to evaluate the utility of the membrane. biotinylation procedure by demonstrating that biotinylated proteins indeed represent membrane proteins; anc that their 2-D patterns are informative with respect to cellular lineage and differentiation state; and that it if feasible to apply this procedure for the selective biotinylation of membranes in intact tissue. Achievement o these milestones will lead in the R33 phase to further optimization of biotinylation procedures; to the development of a database of identified membrane proteins and of their expression patterns, to serve as; resource for other investigators; and to the development of liquid chromatography based procedures for the separation of biotinylated proteins coupled with their mass spectrometry based identification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIBODY RESPONSE TO BINDING REGION OF HIV-1 P17 TO REC Principal Investigator & Institution: Popovic, Mikulas; None; University of Md Biotechnology Institute Baltimore, Md 212023101
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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The HIV-1 matrix protein (MAp17) plays an essential role in the viral life cycle. In addition, this structural protein also has extracellular functions manifested in vitro mainly by enhanced T-cell proliferation, HIV1 replication and proinflammatory cytokine production. We have found that the MAp 17 exerts its biological activities via binding as yet to an unidentified cell surface receptor expressed on peripheral blood-derived mononuclear cells. Mouse antibodies generated to the receptor-binding region (RBR) of the MAp 17 blocked binding to the receptor and abrogated the extracellular effects. Moreover, asymptomatic HIV-1 infected individuals, in contrast to AIDS patients, frequently recognized a potent B cell epitope located at the N-terminus of MAp17, which overlaps with the RBR. Based on these observations, we hypothesize that HIV-1 positive asymptomatic individuals with slower progression towards AIDS generate antibody responses to the RBR of the MAp 17, and these antibodies block MAp 17 binding to its receptor. To address the role of these blocking antibodies in the pathogenesis of AIDS a sensitive serological assay will be developed. The assay will be based on measurements of biotin-conjugated MAp 17 binding to cells using flow cytometry. The establishment of the methodology will proceed as follows: (1) development of a binding assay suitable for assessment of sera from immunized animals to block the specific binding of the MAp 17 to its receptor. Important steps in this stage of the binding assay development are: (a) identification of a permanent cell line suitable for MAp17binding; (b) optimization of blocking the MAp 17 interaction with its receptor using antibodies to the MAp 17; (c) assessment of antibodies that recognize the functional/B-cell epitope region, termed also functional RBR, in MAp17pep scan analyses; and (d) testing of these antibodies to neutralize MAp 17 capacity to induce proinflammatory cytokine production; (2) evaluation of applicability of the binding assay for detecting antibodies with capacity to block MAp 17 binding to its receptor in sera from individuals positive for HIV-1p 17/p24. The binding assay for assessment of human sera will include the following important steps: (a) using human sera, we will reassess the optimal conditions for blocking of MAp 17/receptor interactions that were determined in the testing of sera from immunized animals; (b) testing the capacity of sera to recognize the functional RBR in the MAp 17 pep scan analyses; and (c) evaluate RBR positive human sera to neutralize capacity of MAp 17 to induce the proinflammatory cytokine production. The binding assay development using sera from MAp 17 immunized animals will be performed in the first year and its applicability for testing HIV-1 (MAp17) positive human sera will be performed in the second year of the project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASPECTS OF BIOTIN NUTRITION Principal Investigator & Institution: Mock, Donald M.; Professor; Biochem and Molecular Biology; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-MAR-2007 Summary: Long term goals of this project are to determine the biotin requires for normal individuals in circumstances in which biotin status may be impaired and to investigate the consequences and pathogenic mechanisms for marginal biotin deficiency. We recently demonstrated that marginal biotin deficiency is common during normal human gestation and have demonstrated that marginal deficiency is quite teratogenic in mice. Thus, the following five specific aims are relevant and timely. In Specific Aim #1, we will test the hypothesis that maternal biotin deficiency causes abnormal development of fetal skeletons and palate by causing deficient fetal activity of
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the biotin-dependent enzyme acetyl- CoA carboxylase which leads in turn to deficiency of arachidonic acid and prostaglandin. In fetal palate and limb bud explants from biotin deficient and sufficient CD-1 mice, we will quantitative fetal arachidonic acid component and synthesis rates and will examine the malformation ameliorating effects of supplementation of arachidonic acid and prostaglandin and the amelioration blocking effects of cyclooxygenase inhibitors. Analogous studies will also be conducted in vivo. In Specific Aim #2, we will test the hypothesis that infants with cleft plate or limb shortening have significantly reduced biotin status compared to normal infants. In a case-controlled study, biotin status will be assessed in cord blood using odd-chain fatty acid composition in red blood cell membranes and plasma and lymphocyte activity of the biotin-dependent enzyme propionyl-CoA carboxylase. In Specific Aim #3, we will clone and sequence a biotin transporter recently discovered in our laboratory. In studies of cells from the first individual with biotin transporter deficiency, we will investigate the molecular nature of the genetic defect. In Specific Aim #4, we will confirm promising new indicators of biotin status and investigate the validity of the expression of particular biotin- related genes (e.g., carboxylases) as indicators of marginal biotin deficiency in healthy adults rendered marginally biotin deficiency by egg-white feeding. In Specific Aim #5, we will determine the subcellular localization of the enzyme(s) responsible for catalyzing the beta- oxidation of biotin to the inactive metabolite bisnorbiotin and characterize this pathway. Understanding of this pathway is important because accelerated biotin catabolism may be the major cause of biotin deficiency in pregnancy and anticonvulsants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSEMBLY AND AXONAL TRANSPORT OF NEUROFILAMENT PROTEINS Principal Investigator & Institution: Brown, Anthony; Associate Professor; Neurobiotechnology Center; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Neurofilaments are thought to play a central role in the etiology of a number of human neurodegenerative diseases, most notably amyotrophic lateral sclerosis. These disorders are characterized by massive accumulations of neurofilaments in the axons of affected neurons, leading to axonal degeneration. The accumulation of neurofilaments in these diseases is thought to be caused by changes in the mechanisms of slow axonal transport which move cytoskeletal and cytosolic proteins along axons from their site of synthesis in the cell body. However, these mechanisms are poorly understood and controversial. The principal issue concerns the site of assembly of cytoskeletal proteins and the form in which they move. The polymer transport hypothesis proposes that the cell body and proximal axons are principal sites of assembly of cytoskeletal proteins and the form in which they move. The polymer transport hypothesis proposes that the cell body and proximal axon are principal sites of assembly and that cytoskeletal proteins are transported in the form of moving polymers. In contrast, the cytoskeletal proteins are transported in the form of subunits of oligomers that assemble locally along the axon and the axon tip. To test these hypotheses, the assembly and axonal transport of neurofilament proteins will be investigated in cultured neurons, which are advantageous because of their accessibility to direct observation and experimentation. The proposed experiments will address two specific aims. For Specific Aim 1, immunofluorescence and immunoelectron microscopy will be combined with quantitative digital image analysis to determine the sites of assembly of biotinylated and
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endogenous neurofilament proteins in neurons. For Specific Aim 2, novel strategies that include constriction that includes constriction of axons will be combined with direct observation of fluorescent neurofilament proteins in living cells to determine the form in which neurofilament proteins are transported. The long-term goal of this research is to determine the mechanism by which neurofilament proteins move in axons and the mechanisms that lead to the accumulation of neurofilaments in certain neurodegenerative diseases. By testing specific hypotheses on the assembly and axonal transport of neurofilaments, the studies proposed here represent an important step toward this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSEMBLY AND FUNCTION OF BIOLOGICAL IRON-SULFUR CLUSTERS Principal Investigator & Institution: Johnson, Michael K.; Distinguished Research Professor of Chem; Chemistry; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: (Adapted from applicant's abstract) Iron-sulfur clusters are present in more than 120 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Although their primary role lies in mediating biological electron transport, iron-sulfur centers are known to constitute the active sites of numerous enzymes and to have important structural and regulatory roles. However, the functional diversity of biological ironsulfur clusters has yet to be fully defined, and the mechanism of cluster biosynthesis, which is central to cellular iron homeostasis and the regulatory roles of iron-sulfur clusters, is still poorly understood. The long-term goal of this project is a molecular-level understanding of cluster biosynthesis and of the newly emerging roles of biological iron-sulfur clusters in disulfide reduction, initiating radical reactions in Sadenosylmethionine-dependent enzymes, and providing the sulfur for biosynthesis of biotin and lipoic acid. Ultimately this will lead to enhanced understanding of iron homeostasis and human diseases related to iron overload and defects or inhibition of respiratory chain enzymes. The approach involves using molecular biology techniques to effect large scale expression and/or site-specific changes in the target enzymes and proteins, biochemical and enzymatic assays, and the application of biophysical spectroscopic techniques (electron paramagnetic resonance, absorption, magnetic circular dichroism, resonance, absorption, magnetic circular dichroism, resonance Raman, Mossbauer and mass spectrometry) that can probe the nature and detailed properties of iron or iron-sulfur centers during catalytic cycling or cluster biosynthesis. The specific systems to be investigated include the proteins involved with nitrogenfixation-specific and general iron-sulfur cluster biosynthesis in Azotobacter vinelandii, biotin synthase from Escherichia coli and ferredoxin:thioredoxin reductase from chloroplasts. The objectives are to establish the mechanism of NifU/NifS- and IscU/IscS-mediated iron-sulfur cluster biosynthesis, determine the role of the ironsulfur cluster in ferredoxin:thioredoxin reductase in mediating reductive cleavage of the active-site disulfide, characterize the cluster transformation that is responsible for providing the sulfur for biotin biosynthesis, determine the mechanism of iron-sulfur cluster-mediated reductive cleavage of S-adenosylmethionine in biotin synthase, and develop an in vitro catalytic system for biotin biosynthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BINDING PROTEINS FOR COMPOUNDS WITH VITAMIN A ACTIVITY Principal Investigator & Institution: Ong, David E.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-1983; Project End 31-AUG-2006 Summary: (provided by applicant): The long-term goals are to understand the roles of specific binding proteins in vitamin A absorption, transport, and metabolism. A novel retinoic acid (RA) synthesizing system, co-expressed with cellular retinoic acid binding protein (II) (CRABP(II), has been identified in the female reproductive system and in human mammary epithelium. CRABP (II) and cellular retinoic acid binding protein (CRABP) have been demonstrated to be associated with the mitochondria. Specific studies to build on these observations are: (1) to determine the distribution/regulation of this and other RA synthesizing systems in rat tissues, and to characterize the RA synthesizing enzymes in human mammary epithelium to examine defects in tumororigenic cell lines; (2) to delineate the novel mechanisms of mitochondria association of the two retinoic acid binding proteins; (3)to access the role of mitochondria in retinoid metabolism; and (4) to reveal the participation of CRABP (II) in these processes. Experimental designs and methods are: (1) sites of expression of CRABP (II) and RA-synthesizing enzymes I epithelial linings of rat tissues will be revealed by immunohistochemistry and in situ hybridization. The effect of vitamin A deficiency on expression will be examined. (2) Sequences involved in mitochondrial association will be identified for CRABP and CRABP(II). Alanine-scanning mutagenesis will define the residues essential for association. Mitochondrial association will be followed by confocal microscopy of the pattern of immunofluorescence of proteins or of peptide fusions with green fluorescent protein for FLAG tag. Sequences established as important will be chemically synthesized with a photoactivatable group and attached biotin, incubated with mitroochondria and cell extracts and cross-linked to allow identification of proteins involved in recognition. (3) Appropriate mitochondria will be tested for ability to metabolize retinoids. Metabolities will be identified, including possible novel metabolities that might served as ligands for the retinoic acid nuclear receptors. (4) CRABP(II) will be mutated to ablate targeting to the mitrochondria to see if this "loss of function" affects retinoid metabolism and movement in cells normally expressing this protein. These studies will increase our understanding of the essential role of retinoids in maintaining many epithelia, particularly epithelial prone to pathological conditions such as cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSISTORS
BIOCHEMICAL
DETECTION
WITH
SINGLE-ELECTRON
Principal Investigator & Institution: Brousseau, Louis C.; Quantum Logic Devices 7801 N Lamar, Ste D-98 Austin, Tx 78752 Timing: Fiscal Year 2002; Project Start 17-JUL-2001; Project End 30-SEP-2003 Summary: (provided by applicant) This application describes the extension of singleelectron transistors (SET's) to biochemical detection. Theses devices are sensitive to even single-molecular binding events and use very little power. Fabricated with standard silicon micromachining techniques, they are rapidly and inexpensively produced, and easily adaptable to specific application requirements. This project will demonstrate their use in monitoring the coupling of biotin/steptavidin, as well as DNA oligomer hybridization in order to demonstrate the effectiveness of SET's for biological research
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(microarrays), medical diagnostics, and biochemical warfare defense. PROPOSED COMMERCIAL APPLICATION: This device will have commercial potential in the areas of point-of-care medical diagnostics, biological research, genomics, and biochemical warfare defense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOSPECIFIC POLYMER ENZYME CONJUGATES FOR DRUG DELIVERY Principal Investigator & Institution: Kwon, Glen S.; Associate Professor; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 08-JAN-2001; Project End 31-DEC-2004 Summary: (Applicant's abstract) Once a target location has been identified for a drug, protein or gene, proper spatial and temporal control in the delivery of these molecules is a fundamental problem in biomedical engineering. In one promising approach for anticancer drugs called antibody-directed enzyme prodrug therapy (ADEPT), a monoclonal antibody (MAb)-enzyme conjugate selectively binds an antigen expressed on tumor cells, and the enzyme moiety releases drug from the subsequently injected prodrug at the target site. ADEPT is in clinical trials. However, drawbacks of MAbenzyme conjugates limit ADEPT. They express low chemical and physical stability, short blood-half life, immunogenicity and low tumor to blood ratio. Attaching a common water-soluble polymer, methoxy-terminated poly(ethylene glycol) (PEG), onto MAb-enzyme conjugates enhances stability, prolongs blood circulation and reduces immunogenicity, but with no marked increase in tumor to blood ratio. Our research will focus on biospecific polymer-enzyme conjugates and their role in ADEPT. We attached a biotinylated PEG on a model enzyme, carboxypeptidase A (CPA). A biotin moiety at a chain end of PEG may mediate several useful functions for the first time for a PEGenzyme conjugate. A biotin moiety may mediate the separation of PEG-CPA conjugate by affinity chromatography, fractionating in terms of number of attached biotinylated PEG on CPA using an immobilized monomeric avidin. A biotin moiety may tether an antibody in conjunction with biotin and streptavidin. Lastly, a biotin moiety may bind a clearing agent (e.g., streptavidin) in blood, an interaction that may mediate the clearance of biotinylated PEG-CPA conjugate by the liver and an increase in its tumor to blood ratio. The specific aims of the proposal: (1) To prepare a biotinylated PEG-CPA conjugate with controlled levels of biotinylated PEG at varied molecular weight by reductive amination and by affinity chromatography with immobilized monomeric avidin. (2) To study the catalytic activity and the stability of fractionated biotinylated PEG-CPA conjugates. (3) To study the immunogenicity and the plasma profile of fractionated biotinylated PEG-CPA conjugates in mice, focusing on their clearance by streptavidin. (4) To tether an IgG1 (174H.64) together with biotin and streptavidin on biotinylated PEG-CPA conjugate with optimized properties, purify the conjugate to obtain a 1:1 complex, study its stability, and assess target cell binding in vitro. (5) To study the plasma profile and the biodistribution of antibody-biotinylated PEG-CPA conjugates ("active" targeting) and biotinylated PEG-CPA conjugates ("passive" targeting) in tumor-bearing mice (KLN-205), assessing the effect of injected streptavidin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOSYNTHESIS AND NOVEL FUNCTIONS OF FE-S CLUSTERS Principal Investigator & Institution: Huynh, Boi-Hanh V.; Professor of Physics; Physics; Emory University 1784 North Decatur Road Atlanta, Ga 30322
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Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-MAR-2005 Summary: (provided by applicant) Fe-S proteins are a group of functionally diverse proteins that contain prosthetic groups composed of Fe and inorganic sulfur of various structures, termed Fe-S clusters. In addition to the well-established role of electron transport, Fe-S proteins are involved in a diverse range of non-redox processes including sensing and regulatory functions. In this application, we propose to employ a combined spectroscopic/rapid-kinetic approach to investigate the biosynthesis of Fe-S clusters and to study the newly discovered functional role of Fe-S cluster in stabilizing radical intermediates. It has been established that a pair of the nitrogen fixation gene products, NifU and NifS, are essential for the assembly of the Fe-S clusters for the nitrogenase enzyme system. Homologs of NifS and NifU, termed IscS and IscU, respectively, are found in a wide spectrum of living organisms ranging from bacteria to human, and thus, have been proposed to be involved in the general assembly/repair of Fe-S clusters in biology. Here, experiments are proposed to investigate the mechanism of Fe-S biosynthesis and to establish the roles play by NifU/NifS and IscU/IscS in this important biological process. For the purpose of enhancing our understanding of Fe-S cluster functions, three functionally diverse proteins were chosen for the proposed studies: pyruvate formate-lyase activating enzyme (PFL-AE), ferredoxin: thioredoxin reductase (FTR) and biotin synthase. PFL-AE activates pyruvate formate lyase (PFL) by catalyzing the generation of a glycyl radical in PFL. FTR catalyzes the reductive cleavage of disulfide groups in thioredoxins for enzyme activations, and biotin synthase converts dethiobiotin to biotin. Evidence accumulated so far suggests that all three enzymes employ a 4Fe-4S cluster-mediated site-specific u(3)-S(2-) based chemistry for their respective functions. The proposed study is designed to evaluate the validity of this suggestion and to determine the detailed mechanistic steps involved in the catalytic cycles. The methods of choice for the proposed studies are Mossbauer and EPR spectroscopies, which are particularly suited for the study of Fe-containing proteins. Rapid freeze-quench kinetic techniques will be used to trap reaction intermediates for spectroscopic characterization and for kinetic investigations. Whenever possible, other complementary techniques, such as resonance Raman, ENDOR, and EXAFS will be used to obtain further structural information on the reaction intermediates. Site-specific variants will be engineered, produced and subjected to similar kinetic/spectroscopic investigations for the purpose of defining the functional roles of specific residues. Detailed mechanistic insights at a molecular level are expected to emerge from the proposed investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER THERAPEUTICS THAT ANCHOR PROTEINS TO MEMBRANES Principal Investigator & Institution: Peterson, Blake R.; Chemistry; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2003; Project Start 01-JAN-2000; Project End 31-DEC-2007 Summary: (provided by applicant): Multidrug resistant (MDR) cancer remains the primary impediment to curative cancer chemotherapy. MDR cancer cells differ from typical tumor cells by dramatically upregulating production of several factors including the drug transporter P-glycoprotein, the cholesterol binding protein caveolin, and components of lipid raft microdomains of cellular plasma membranes. These raft domains are enriched in cholesterol and sphingolipids and play key roles in signal transduction processes. The distinct composition of plasma membranes of MDR cancers may enable selective chemotherapy targeting these cancers. During the last grant cycle,
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novel small molecules were synthesized that comprise cholesterylamine covalently linked to protein ligands such as biotin. These compounds bind lipid rafts in plasma membranes of cancer cells.Treatment of cancer cell lines with a synthetic biotincholesterylamine ligand (ligand #1) and the protein Streptavidin (SA) efficiently targets SA to lipid rafts, resulting in rapid clathrin-mediated endocytosis of this protein-ligand complex. This novel system mimics penetration of cells by Cholera toxin, which binds ganglioside GM1 in lipid rafts. This project is based on the hypothesis that ligand #1 will regulate endocytosis of SA linked to endosome-activated toxins daunorubicin and exotoxin in cancer cell lines. Since ligand #1 binds lipid rafts, selective delivery of SAlinked toxins to lipid raft-rich MDR cancer cells will be investigated in vitro and in vivo in murine cancer models. The effectiveness of ligand #1 at enhancing endocytosis of Satoxins fused to neuropeptide Y, which targets specific receptors on neuroblastoma cells, will also be evaluated. This novel approach directed at enhancing endocytosis of surface receptors by targeting to lipid rafts with small molecules could address the major problem in immunotherapy of non-internalized tumor antigens. The hypothesis that ligand-regulated delivery of SA to antigen presenting cells (APCs) will stimulate immune responses will also be tested. Novel immunostimulants will be investigated by fusing SA to the ovalbumin antigen, regulating endocytosis in APCs with ligand #1, and analyzing T-cell activation. This approach could control immunostimulation at the molecular level and yield novel tools for vaccine development. Recruitment of intracellular avidin fusion proteins to plasma membranes by ligand #1 will also be studied in an effort to conditionally regulate cellular growth and death Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANNABINOID RECEPTORS ON IMMUNE CELLS Principal Investigator & Institution: Klein, Thomas W.; Professor and Vice Chair; Medical Microbiol & Immunology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 15-FEB-1998; Project End 31-JAN-2004 Summary: It is now clear that the brain and immune tissues have a cannabinoid system of receptors and ligands. However, it is not clear how this system is structured and how it affects human physiology and health. This is now a critical issue because the medicinal use of marijuana is gaining political and public support and is now recommended for use in AIDS wasting disease. The overall goal of our research is to understand the immunological effects of cannabimimetics and the natural function of the "immunocannabinoid" system. This proposal is a continuation of a project started in 1998 on defining the cannabinoid receptor (CBR) mRNA expression in murine immune cells. We have been able to show that immune subsets from mouse and human differ in their expression profile ranging from no expression to high expression. Furthermore, activated immune subsets modulate CBR mRNA expression. The present application is an extension of these findings. In Aim 1, we will define the distribution profile of CB1 and CB2, both mRNA and protein, in T cells, B cells, NK cells, and macrophages from mouse tissues and human PBMCs. It is our hypothesis that immune subsets have different basal levels of CBR expression commensurate with the putative role of these receptors in the immunobiology of the cell. Purified subsets will be analyzed by RTPCR, flow cytometry, Western blotting, immunoprecipitation, and biotin labeling of surface proteins. We expect to document the CBR phenotype of key immune tissues. In Aim 2, we will define the changes in the CBR profile following cell activation and possible mechanisms of these changes. It is our hypothesis that CBR gene activity and receptor expression are regulated by the gene activation sequence in immune cells.
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Subsets will be mitogen and cytokine activated and analyzed for receptor expression by protein analysis and real-time quantitative PCR. Because there are at least 5 different mRNAs associated with CB1, variations in exon usage in different immune subsets will be analyzed by transcription analysis, mRNA usage by RT-PCR and RNase protection, and 5' end mapping with 5' RACE. We expect to document changes in the CBR expression profile in activated subsets and to discover the CB1 exon usage pattern. In Aim3, we will define the putative role of the cannabinoid system in cell proliferation, TNF production, and IL-12-induced Th1 activity. It is our hypothesis that these functions are regulated by the "immunocannabinoid" sytem. The experiments proposed will increase our understanding of the imnunobiology of the cannabinoid system and shed light on the health consequences of medicinal marijuana use in HIV disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOSENSORY TRANSDUCTION Principal Investigator & Institution: Van Houten, Judith L.; Professor and Chair; Biology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-MAR-2004 Summary: This is an application for renewal of funding study chemical sensing in Paramecium. This organism is amenable to multiple techniques for dissecting chemosensory transduction mechanisms in chemoreceptor cells: biochemistry, molecular biology, transmission genetics, electrophysiology, behavioral analysis of populations and individual cells. After we disrupt the cell and study its transduction components in vitro, we can often return our study to the level of the intact cell and ask whether our findings have relevance for the physiology of the cell. Also, we know the identity of stimuli, which bind to distinct receptors. In the past funding period, we have accomplished most and gone beyond some of our original specific aims which were to apply molecular, immunological, biochemical and fluorescent dye techniques to the study of the cAMP receptor and the plasma membrane calcium pump, which appears to participate in transduction pathways. We have partial clones of the cAMP receptor gene, and the full length gene for the plasma membrane calcium pump. We have subcloned and studied the pump's calmodulin binding domain. Highlights include There are not 1 but at least 3 transduction pathways, 2 of which involve the calcium pump; attractant stimulus NH4CI has no receptor and rapidly alkalinizes the cell; while all attractant stimuli hyperpolarize the cell, only glutamate increases cAMPI and very rapidly; some chemoreceptors probably are GPI anchored and not integral membrane proteins; biotin is an attractant and its receptor likely is GPI anchored cloned; attractants hyperpolarize cells and the conductances initiated by biotin and acetate have been partially characterized. There is a sustained outward conductance (possibly the pump current) and a large inward conductance for the off-response in biotin; there is an initial inward calcium and outward K conductance in acetate with a small inward conductance for the acetate off-response. The calcium pump appears to sustain the hyperpolarization in both biotin and acetate. We used mutants with conductance defects to test these ideas. We propose to test three hypotheses that arise from our studies. 1) Chemoreceptors for biotin and glutamate are GPI anchored proteins. 2) Chemosensory transduction in 2 pathways in modulates a calcium pump to generate a hyperpolarizing conductance. Gene structure suggests that these modulations involve PKA, PKC or calmodulin. 3) Biotin and acetate induce distinct sets of Conductances, which we will test using voltage clamp analysis of normal, mutant and transformed cells. We will use electrophysiological, biochemical, molecular biology, and immuno-techniques in a
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collaborative effort between two laboratories. These studies should inform the research of others who study sensory transduction in olfaction, taste, chemotaxis and other signaling stems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHIRAL CATALYSTS DESIGNED TO CATALYZE ORGANIC REACTIONS Principal Investigator & Institution: Jacobsen, Eric N.; Professor; Chemistry and Chemical Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2002; Project Start 01-JAN-1991; Project End 31-DEC-2005 Summary: (provided by applicant) This program has as its objectives the discovery, development, and application of selective catalytic reactions of use in organic synthesis. In particular, we seek to identify catalysts for asymmetric reactions of broad synthetic utility, to elucidate the reaction mechanisms of these reactions, and to illustrate their utility through their application in the efficient synthesis of useful building blocks and complex targets. The ultimate goal of this effort is to advance the field of organic synthesis through the development of truly practical catalysts that will find application in both industry and academia for the enantioselective synthesis of biologically important compounds. Four major projects are outlined in this application. We propose to develop novel multimeric metal catalysts that operate on the basis of cooperative reactivity. This will be accomplished through the preparation of conformationally constrained oligomeric complexes wherein the relative orientation of catalyst units can be tuned through conformational control of the linker units. We will also explore the possibility of generating synthetically accessible self-assembling multimeric catalysts that display cooperative reactivity. In a second project, we plan to test a new hypothesis for asymmetric catalysis wherein two different chiral catalyst complexes function cooperatively to catalyze nucleophile-electrophile addition reactions. The goal of this effort is to establish whether reinforced stereoinduction and reactivity effects may open the door to valuable new reactions. A third project is focused on the investigation of the mechanism and scope of a novel class of non-metal catalysts. We recently applied a parallel library approach to the discovery of extraordinarily general non-metalcontaining catalysts for imine hydrocyanation. Preliminary studies indicate both a fascinating enzyme-like mechanism of action of these novel catalysts, and a highly promising level of generality in other synthetically useful reactions. In a fourth area of effort, we plan to investigate new classes of chiral catalyst systems, and two new research directions are described. One involves the design of effective chiral imidazolium carbene ligand systems for late-transition metal catalyzed reactions. A second is focused on the discovery of self-assembling biomimetic oxidation catalysts, and their development into synthetically useful systems for enantioselective epoxidation of alkenes with hydrogen peroxide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--ELECTROPHYSIOLOGY AND HISTOLOGY Principal Investigator & Institution: Yoshikami, Doju; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: The electrophysiology component of this Core will screen conotoxins for their functional activities against known ion channel targets as well as identify possible new targets for novel conotoxins. This will be pursued at three levels, with each
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succesive level having decreased scope but increased specificity. A) Extracellular recording from skeletal muscle and motor, sensory, and sympathetic nerves in isolated tissue preparations will be used to obtain a global assessment of a toxin's activity. B) Whole-cell voltage clamping of dissociated neurons will be used to focus in on the general nature of the channel affected by the toxin (e.g., Navs K; fast- vs slowinactivating, etc.). C) The specific channel isotype targeted by the toxin will be pinpointed by examining the toxin's effect on cloned channels expressed in Xenopus oocytes. Levels B and C will also address the mechanism of toxin-action. The histology component of the Core will identify the sites of conotoxin binding in excitable tissues by light microscopy. Toward this end, conopeptides will be labeled with the following reporter groups: (a) fluorophores, for direct viewing by fluorescence microscopy; (b) 125I, for use with autoradiography and viewing by dark field microscopy; and (c) biotin, for use with avidin conjugated to HRP for histochemical staining and avidin conjugated with fluorophores for fluorescence microsocopy. These experiments assessing the locations of the cellular and subcelluar binding sites of toxins will complement the physiological experiments assessing the toxins' effects on target function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--IMAGING AND MICROSCOPY Principal Investigator & Institution: Kim, Ji-Yong Julie.; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The goal of the Imaging and Microscopy Core is to provide assistance with histological tissue processing, in situ hybridization assays, immunofluorescent staining, and image analysis. Training opportunities in modern histochemical methodology will also be available. By providing these services as well as reagents, the core will facilitate progress toward each project proposed by the PI's/Co-PI's of this Center grant. A centralized core will provide standardized results and savings in time, costs and invaluable team resources. The Imaging and Microscopy Core will: 1. Provide equipment and technical services for the acquisition of frozen and fixed tissue sections. The investigators provides the tissue and the Core than has the microtomes, cryostat, dry ice, and other supplies needed to cut the tissue. 2. Provide a "Tissue-In-Slide-Out" service for frozen or fixed tissues. For immunocytochemistry (ICC), the investigator would provide the primary antibody and the experimental tissue. Detailed protocols for immunohistochemical (both fluorescence and avidin-biotin complex (ABC) staining) and in situ hybridization histochemical techniques will be available for those who wish to do the processing themselves. A fully automated tissue processor and computerized staining system will be purchased. 3. Provide a bank of baboon and human tissues for histochemical processing. Frozen sections and plastic or paraffin embedded tissues will be available. 4. In liaison with the Tissue Procurement/Cell Culture Core, the Imaging and Microscopy Core will fix human endometriosis tissues as needed and provide paraffin embedded sections. 5. Provide facilities for image processing and data analysis through state of the art image analysis equipment, including a state-of-the-art SPOT digital camera that is linked to a PC based imaging analysis system (Image Pro Plus 4.o). The microscope is equipped for bright field, dark field, and immunofluorescent analysis. 6. Provide training in immunohistochemistry, and digital image capture, processing and analysis. Dr. Harold Verhage will also provide consultation in immunohistochemistry, morphological analyses, and tissue processing. 7. Prepare tissue samples for investigators who wish to use confocal microscopy and/or electron microscopy at the
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Research Resources Center (RRC) of the University of Illinois, which is fully equipped with state-of-the-art equipment. 8. Future development in conjunction with the Laser Capture Mcrodissection (LCM) facility. As a future development, we will become conversant in the use of this machine and ultimately provide services for the appropriate preparation of tissue samples to used with the LCM. This technique requires special preparation and fixation of tissues to optimize single cell analysis at the molecular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--IMMUNOLOGY Principal Investigator & Institution: Witztum, Joseph L.; Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): Hybridoma Core (Scripps): The responsibilities of the Hybridoma Core are to generate, characterize and maintain monoclonal antibodies for use by all investigators. Specific services include: 1) immunization and bleeding of mice; 2) cell fusion; 3) primary and secondary screening assays (in collaboration with UCSD as needed); 4) cell cloning; 5)ascities fluid production; 6) cell maintenance, freezing and storage; 7) cataloging antibody storage; 8) antibody purification (in collaboration with the UCSD facility); and 9) Immunoglobulin heavy chain identification. Detailed methodologies for each of these techniques have been published previously. More than 250 hybridomas have been generated, cloned, characterized and maintained over the lifetime of this SCOR collaboration, and more than 24 in the last 4 years. Immunology Core (UCSD): The Immunology component at UCSD is responsible for preparation of immunogens used to generate antisera, as well as those used to immunize mice at the Hybridoma Core at Scripps. We use guinea pigs almost exclusively for antisera generation as we have found that they reliably yield high-titered antisera. In fact, we routinely use only 2 guinea pigs per immunization. The Core lab immunizes guinea pigs and determines titers, characterizes the pre- and postimmune antisera, purifies specific immunoglobulins when necessary and stores and catalogues them. Antigens range from isolated apoproteins to fusion proteins to putative receptors, etc. Often such highly purified antisera prove superior even to monoclonal antibodies, for example for cell-injection studies conducted by Drs. Glass, Rosenfeld and colleagues. The UCSD component of the Core also prepares a wide variety of immunological reagents to be used by the other Units, such as primary or, secondary antibodies to be used in immunoassays or Western blots or FACS analysis, and also participates in the purification of antibodies as needed. In addition, the Core will facilitate the selection of polypeptides to be synthesized to make reagent-specific antibodies, which are generated by conjugation to appropriate carriers, such as KLH. For example, we generated peptide-specific antibodies to macrosialin as noted above. During the past four and a half years, we have used 226 guinea pigs to generate antisera to 113 antigens for use by SCOR investigators. We also label antibodies with enzymes, such as alkaline phosphatase or with biotin which can then be used by the different Units for various chemiluminescent assays, Western blots, or for FACS analysis. Finally, an important component of the Immunology Core is to assist investigators and to train new postdoctoral fellows in immunological techniques, both by providing reagents as well as assistance in setting up assays and instructions in use of the chemiluminescent methodologies that we have adapted for all assays. For example, we have utilized commercial reagents for analysis of cytokines, and by use of chemiluminescent techniques greatly increased the sensitivity and linearity of the assays.
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Biotin
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COVALENTLY REACTIVE CD4 MIMETICS FOR INHIBITION OF HIV Principal Investigator & Institution: Hanson, Carl V.; Research Scientist; Public Health Foundation Enterprises City of Industry, Ca 90638 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Therapeutic administration of soluble CD4 is theoretically an attractive means of competitively inhibiting the binding of HIV to its primary cellular receptor, but was a failure in clinical trials more than a decade ago. We propose the creation of novel CD4 analogs to overcome the stoichiometric and affinity limitations of that initial approach. Using electrophilic phosphonate ester probes, we recently discovered that HIV gp120 contains activated nucleophilic amino acids. In the proposed studies, CD4 (and CD4 peptide mimetic, s) will be modified by the addition of activated electrophilic phosphonates, which will result in specific covalent bonding of these constructs to nucleophilic sites on gp120 on the surface of HIV virions. Such an "infinite" affinity interaction will result in irreversible blocking of HIV infectivity. The concept is based on our successful analogous work on catalytic antibodies, in which nucleophilic immunoglobulin sites bind to electrophiles in the substrate ligand. Thus the Specific Aims of this proposed Innovation Grant are (1) to create covalently reactive CD4 and CD4 peptide mimetics; (2) to determine the potency, intra- and intersubtype breadth and irreversibility of HIV neutralization and inhibition of cell-to-cell spread of HIV infection via cell fusion by these covalently reactive CD4 analogues; (3) to demonstrate the irreversibility of binding of the constructs to gp120 and to intact virions; and (4) to determine the role in the virus neutralization that isplayed by the covalency (vs. conventional noncovalent antibody binding). Successful results should lead tofollow-up testing in primate models and human clinical trials. The proposed studies may also help to definecovalent and pseudocovalent forces as a novel mechanism of protein-ligand interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEFERIPRONE THERAPY FOR SICKLE CELL DISEASE Principal Investigator & Institution: Olivieri, Nancy F.; Director, Hemoglobinopathy Program; Uhn Toronto General Hospital 200 Elizabeth St, Ccrw1-800 Toronto, Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract) This research study is designed to determine if administration of the orally active iron chelator deferiprone can ameliorate the chronic hemolytic anemia of sickle cell disease by inhibiting iron-induced oxidative damage to the sickle erythrocyte membrane and decreasing red cell destruction. The cytoplasmic surface of sickled cells has been shown to carry abnormal deposits of free iron, capable of generating free hydroxyl radicals that induce protein thiol oxidation and lipid peroxidation leading to cation leak, cell dehydration, reduced erythrocyte deformability, and premature red cell destruction. Removal of iron from the red cell membrane would be expected to reduce the generation of hydroxyl radical, and represents a novel approach to the therapy of sickle cell disease. Preliminary studies with the orally active iron chelating agent deferiprone (L1) have demonstrated the utility of this agent in the removal of free iron deposits from membranes of red blood cells in vitro and in vivo. In the proposed studies the dose, schedule of administration, and pharmacokinetic profile of deferiprone that will be most effective in the removal of
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erythrocyte membrane free iron and that which achieves maximal sustained plasma drug concentrations of deferiprone will be established, and improvement in biotin red cell survival, ferrokinetic measurements of erythron transferrin uptake, and abnormalities associated with oxidative denaturation of hemoglobin and lipid peroxidation within red cells in patients with sickle cell disease treated with an extended period of deferiprone under the optimal dosing regimen will then be examined. The combination of determinations of red cell survival using biotinylated erythrocytes and of ferrokinetic measurements of erythron transferring uptake will provide a comprehensive assessment of red cell production and destruction in patients with sickle cell disease, before and after extended therapy with deferiprone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF NOVEL GOLD BINDING FUSION PROTEINS Principal Investigator & Institution: Irani, Meher; Biohesion, Inc. 1208 Ne 100Th St Seattle, Wa 98125 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The ability to directly and uniformly immobilize proteins onto detection surfaces in a robust and simple way, with full retention of biological activity is a highly coveted goal in the field of bioengineering. It leads to the development of high value devices and applications which will have a tremendous impact on basic research, drug discovery, diagnostics and biodetection. An excellent way to achieve this is to use the property of known gold binding peptides to strongly adhere to gold surfaces under very mild binding conditions and to covalently attach any desired target protein to such peptides by recombinant means. The specific aims of this proposal are: a) to test the feasibility of producing gold binding peptides in Escherichia coli as fusion proteins with molecules of biological and commercial relevance such as protein A and streptavidin; b) to optimize the expression and purification conditions; c) to characterize and optimize gold binding of the fusion proteins; d) to construct and characterize biosensors with these recombinant fusion proteins. The long-term aim of this project is to expand the expression capabilities to a host of other molecules of biological and commercial significance and develop biosensing devices and assays for a wide variety of applications of considerable commercial potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIPYRIDAMOLE/MAGNESIUM TO IMPROVE SICKLE CELL HYDRATION Principal Investigator & Institution: Kalinyak, Karen A.; Medical Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 11-JUL-2003; Project End 31-MAR-2008 Summary: Vaso-occlusivc episodesare common among patients with sickle cell anemia (SCA), causing pain and chronic organ damage. SCA is characterized by the presence of dense, dehydrated sickle red blood cells (SS RBC), which are rheologically abnormal and are selectively trapped during vaso-occlusion. Strategies to prevent cellular dehydration would offer important therapeutic options that might decrease vaso-occlusive episodes. SS RBC dehydration results from cation depletion mediated by two cation transport systems, a sickling-induced (SI) leak pathway and the KCI cotransporter (KCC). Previous work at this Center has shown that di-pyridamole inhibits the SI fluxes of Na, K and Ca in vitro. Increasing cellular magnesium inhibits KCC activity and increases cellular hydration in animal models of SCA. A small clinical study in SCA patients
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Biotin
demonstrated that Mg supplementation increased cellular Mg, reduced KCC activity and improved red cell hydration. This study will test the hypothesis that significant reduction in SS RBC dehydration will be seen in patients with SCA treated with either dipyridamole or magnesium. An additive, and possibly synergistic, effect on dense cell formation is hypothesized in patients treated simultaneously with both agents. A prospective, randomized, crossover, repeated measures design will be conducted among 48 patients with SCA, ages 12 years and older. Patients will be recruited from the Cincinnati Comprehensive Sickle Cell Center and the Sickle Cell Program at Wayne State University in Detroit. This design will allow for efficient comparison of the three treatment options; dipyridamole alone, magnesium alone or a combination of both. We anticipate that these therapies will be well tolerated by the patients. Primary outcome measures include the number of dense cells, assessed by automated cell counting and phthalate density gradients, cellular cation content, cell volume and hemoglobin concentrations. Using the biotin label technique pioneered in Cincinnati, measurements of red cell survival and rate of dense cell formation will be made in six patients in each treatment group, and will shed light on the mechanisms underlying SS RBC dehydration and its postulated inhibition by dipyridamole and Mg. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTRON PARAMAGNETIC RESONANCE SPECTROMETER Principal Investigator & Institution: Warncke, Kurt; Associate Professor; Physics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The objective of this application is to request a Bruker BioSpin Corporation Elexsys E560 continuous-wave electron paramagnetic resonance (EPR) spectrometer with 10" electromagnet/12 kW power supply that will operate at X-band (9-10 GHz) and Q-band (34 GHz) microwave frequencies, and include the electron-nuclear double resonance (ENDOR, TRIPLE) accessories for X- and Q-band. Also requested are cryostats for operation at liquid helium and nitrogen temperature, to adjust to the different relaxation properties of the paramagnets, and a goniometer for single crystal studies. The new instrument would replace an aging EPR spectrometer system. The user group includes the PI, an experienced EPR spectroscopist, and three other Major Users and two Minor Users. The instrument will support the NIH-funded research of four users (5 R01 grants), the pending NIH-funded research of one user, and the preliminary studies of another. The proposed EPR/ENDOR projects include the following: (a) determination of the molecular mechanism of electrondeficient radicalmediated catalysis in coenzyme B12-dependent enzymes, (b) investigation of the emergent novel biological functions of iron-sulfur clusters in biotin synthase, pyruvateformate lyase activating enzyme, and ferredoxin:thioredoxin reductase, in combination with Mossbauer spectroscopy, (c) the mechanism of biotransformation of aromatic hydrocarbons by toluene monooxygenases, by examining metal site structure in single crystals in combination with protein X-ray crystallography, (d) the structure and function of flavoenzymes, (e) determination of the role of divalent metals in the mechanism of fibrillogenesis in amyloid formation, and (f) characterization of the mechanism of radical-mediated DNA strand scission and histone modification by novel organometallic complexes. Operation at Q-band is justified by the need for enhanced resolution of both EPR and ENDOR spectra, and the dual X- and Q-band operation is essential for success of multi-frequency approaches to constrain spectral simulation analyses. The projects supported by the requested EPR spectrometer cover investigations of the wide range of recognized biological radical reactivity, from
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"programmed" essential radicals in enzymes, to deleterious effects of free radicals and metals, to the use of radical reactivity as a therapeutic tool. A sustained high impact of the EPR spectrometer on biomedicine is therefore anticipated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCED T AND B CELL RESPONSES VIA RECOMBINANT PROTEINS Principal Investigator & Institution: Gosselin, Edmund; Assistant Member; Alld Health Education Programs; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract) A safe and successful vaccine against HIV will likely require the simultaneous priming of both cellular and humoral immune responses, and will preferentially involve the use of recombinant proteins. Targeting immunogens to Fc gamma receptor type I (FcgRI) on antigen presenting cells (APC) significantly enhances T cell activation in vitro, and antibody production in vivo. In addition, it can also lead to simultaneous priming of both cytotoxic and helper T cell responses. Furthermore, by combining the administration of antigen with cytokines, T cell activation can be further enhanced, and T cell subset development modulated. It has also been demonstrated that targeting antigen (Ag) to FcgRI on APC can eliminate the need for traditional adjuvant, easing difficulties associated with vaccine preparation and distribution. Therefore, developing a strategy which facilitates antigen targeting to APC, and the use of cytokines in vaccines, is likely to have a significant impact on current vaccine technology, in particular as it applies to HIV. We propose to utilize molecular techniques, and FcgRI-specific constructs, to create and test the ability of a prototype two component (modular) immune targeting system to stimulate enhanced humoral, CD4 helper T cell, and CD8 cytotoxic T cell responses in vitro and in vivo. Components will consist of a humanized divalent FcgRI-specific biotin-binding targeting element, and biotinylated functional elements including Hepatitis B Ag, gp120 Ag, and IL-2. The ability of the two component immunogens to modulate human CD4 and CD8 T cell responses in vitro, and murine B cell, CD4 T cell, and CD8 T cell responses in vivo, will be examined. In the latter instance, transgenic mice that express human FcgRI will be immunized with two component immunogens. Following immunization, CD4 and CD8 T cell responses, as well as the generation of Ag-specific antibody will be measured. These studies will provide a novel and safe approach for simultaneously priming humoral and cellular responses in vivo using recombinant proteins. This approach will not only provide an effective means for controlling the spread of HIV, but many other infectious organisms as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ERYTHROPOEITIN PHYSIOLOGY AND PHARMACOLOGY IN INFANTS Principal Investigator & Institution: Widness, John A.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: The many red blood cells (RBC) transfusions administered to preterm infants as treatment for anemia are expensive and pace them at risk for blood-borne infections and other transfusion related complications. The long-term objectives of Project #1 is to develop effective strategies for optimally administering recombinant human erythropoietin (r-HuEPO) in the treatment of anemia of prematurity. Achieving this
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Biotin
goal is important and timely because r-HuEPO remains an evolving clinical therapy without a clear consensus of how, when and for whom it should be used in these patients. Our objective will be accomplished by performed mechanistically based EPO pharmacokinetic (PK) and pharmacodynamic (PD) studies in sheep and human subjects using sensitive and accurate tracer methodologies. Achieving maximal stimulation for erythropoiesis relies in part upon developing a comprehensive understanding of EPO's thus far elusive in vivo metabolism and relies in part upon developing a comprehensive understanding of EPO's thus far elusive in vivo metabolism and its complex PK and PD behaviors. Because plasma EPO concentrations in anemic preterm infants are reduced relative to those in anemic adults, inadequate EPO production has been suggested as a primary underlying mechanism for the anemia these neonates inevitably develop and as justification for r-HuEPO treatment. Based on direct animal and indirect human data, we suggest that inadequate EPO production is not the primary on direct animal and indirect human data, we suggest that inadequate EPO production is not the primary mechanism, but that other mechanisms may be more important. The basis for this speculation is an expanding body of data indicating that EPO's in vivo disposition occurs primarily via a saturable, receptor-mediated process. As an overall hypothesis we speculate that EPO's in vivo PK and PD are determined by the number and affinity of EPO receptors (EPO-R's) located predominantly on the body's expandable pool of erythroid progenitor cells. This hypothesis is consistent with the observation that EPO's PK behavior is non-linear, that EPO elimination is 3 to 4 times greater in premature infants than adults, and that the red marrow occupies a 3- to 4-fold greater volume per kg body weight in young children than adults. Because of their sensitivity and accuracy, PK methodologies utilizing labeled EPO tracers are ideally suited for investigating EPO's non-linear behavior and for directly measuring its endogenous production rate. In addressing our proposal's three aims, 125I-r-HuEPO and biotinylated r- HuEPO and biotinylated r-HuEPO (Bio-EPO) will be administered as tracers in advanced system analysis-based PK and PD studies performed in sheep and humans, respectively. In Aim #1, methods for analysis-based PK and PD studies performed in sheep and humans, respectively. In Aim #1, methods for biotinylating r-HuEPO retaining its PK behavior and for measuring Bio-EPo in tracer amounts will be developed and validated. In Aims #2 and #3, 125I-r-HuEPO tracer methodology will first be applied in vivo experiments in sheep to determine the effect of perturbations in erythropoiesis (i.e., by bone marrow ablation and by phlebotomy-induced anemia and r-HuEPO treatment) on EPO's PK, PD, and production rate. When Bio-EP becomes available as a tracer, similar studies will be conducted in human infant and adult study groups. Knowledge gained about EPO's PK and PD will permit more optimal use of r-HuEPO thus leading to a reduction in the multiple RBC transfusions typically recovered by preterm infants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESSENTIAL ROLE OF BIOTIN IN CELL PROLIFERATION Principal Investigator & Institution: Zempleni, Janos; Nutritional Sci & Dietetics; University of Nebraska Lincoln Lincoln, Ne 685880430 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 31-DEC-2004 Summary: Background: For many human cell types including those of the intestinal epithelium and the immune system, rapid proliferation is essential for normal function. Proliferating cells exhibit increased growth and DNA synthesis which generate nutrient demands. In particular, we have shown that rapidly proliferating lymphocytes increase the uptake of the vitamin biotin five fold, suggesting that cell proliferation generates a substantial increase in biotin demand. This demand might arise from increased
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synthesis of biotin-dependent carboxylases or from biotinylation of histones (or both). Consistent with this hypothesis are our preliminary studies indicating that biotin deficiency causes reduced proliferation and cell cycle arrest. We hypothesize that biotin has an essential role in cell proliferation in some ways analogous to the role of folate in methylation of DNA regulating the cell cycle. Long-term objectives: To elucidate the role(s) of biotin in the regulation of cell cycle progression and to characterize effects of the cell cycle on cellular biotin homeostasis. Specific hypotheses: (1) At certain phases of the cell cycle, lymphocytes increase expression of the biotin transporter gene leading to increased synthesis of transporter and increase of biotin uptake. (2) In addition to holocarboxylase synthesis, biotin is required in a biotinidase-catalyzed, cell-cycle dependent biotinylation of histones. Specific aims: (1) To quantitate biotin transporter mRNA and transport activity in lymphocytes at various phases of the cell cycle. (2) To quantitate biotinidase mRNA, cellular biotinidase activity, and biotinylation of histones at various phases of the cell cycle in lymphocytes from healthy adults and, for purposes of comparison, from biotinidase-deficient patients. (3) To investigate the intracellular trafficking of biotin and carboxylase activities. (4) To characterize the effect of extracellular biotin concentration in the culture medium on the proliferation rate of lymphocytes. Benefits: The proposed research will likely lead to novel insights into the mechanisms that generate the increased biotin requirement of proliferating cells. These studies are the initial step to determine whether biotin plays an important role in histone modification and cell cycle regulation. The basic knowledge generated may well be relevant to teratogenesis and immune dysfunction caused by biotin deficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOURIER OLIGOSACCHARIDES
TRANSFORM
MASS
SPECTROMETRY
OF
Principal Investigator & Institution: Lebrilla, Carlito B.; Professor; Chemistry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 31-DEC-2002 Summary: The analysis of oligosaccharide heterogeneity will be addressed by the development of several complementary analytical methods based on Fourier transform mass spectrometry. Oligosaccharides are involved in a host of biological functions including cell-cell and cell-matrix recognition, hormonal actions, inter- and intracellular trafficking, and protection. However, unlike DNA and proteins where sequence provides nearly all the primary structure, oligosaccharides are characterized by their sequence, linkage, and stereochemistry. Additionally, the large diversity in the monosaccharides due to chemical modification and isomerism, the labile nature of the glycosidic bonds, and the poor intrinsic basicity all combine to make the structural elucidation of oligosaccharides significantly more difficult than other biopolymers. There is currently no analogous method for oligosaccharides with the sensitivity, reliability and accuracy of the Edman degradation for proteins. We propose to develop analytical methods to rapidly elucidate structures in oligosaccharide libraries. The methods will be developed in the study of the jelly coat of the South African toad, Xenopus laevis. X. laevis is an important model for the study of the early stages of fertilization. The jelly coat plays a role in several important processes including the block to polyspermy, prevention of cross fertilization and protection. Collision induced dissociation will be employed to determine structures of the released oligosaccharide alditols. A catalog of structural motifs with their corresponding CID fragmentation pattern (an oligosaccharide fingerprint) will be produced using the structures of known oligosaccharides. From this catalog, the structure of the minor components will be
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determined. Alkaline degradation (AD) will be used to obtain linkage and sequence information of unknown oligosaccharides. AD coupled with matrix-assisted laser desorption/ionization and Fourier transform mass spectrometry has recently been demonstrated in this laboratory to provide sequence and linkage information on a host of model compounds. The method will be further refined for greater sensitivity and shorter analysis time. It will also be coupled with electrospray ionization. This method will be tested with the oligosaccharides of X. laevis. However, its application is aimed towards libraries where little structural information exists. Finally, a method will be developed to eliminate the tedious process of separation prior to analysis. Strong biotinavidin interaction will be the basis for the development of an analyte specific MALDI probe. A probe with immobilized avidin will be used to extract biotinylated oligosaccharides directly from solution for immediate MALDI-FTMS analysis. This method bypasses the long separation process necessary for the isolation of released oligosaccharides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GATING MEMBRANES
OF
PROTEIN
CHANNELS
IN
LIPID
BILAYER
Principal Investigator & Institution: Finkelstein, Alan; Physiology and Biophysics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-JAN-1981; Project End 31-DEC-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GFI-PROTEINS IN HEMATOPOIETIC DEVELOPMENT Principal Investigator & Institution: Orkin, Stuart H.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Growth Factor Independent (Gfi)-genes, Gfi-1 and Gfi-lb, are sites of retroviral insertions in murine lymphomagenesis and encode zincfinger transcription factors. Homologs of Gfi-proteins in C. elegans and Drosophila regulate cell fate decisions in the nervous system. Within the mammalian hematopoietic system Gfi-1 and Gfi-1 b are expressed in a complementary pattern with Gfi-1 highly expressed in granulocytic and lymphoid cells, and Gfi-lb within erythroid and megakaryocytic lineages. Gene targeting experiments from this laboratory demonstrated that Gfi-1 is essential for granulocyte maturation and for down-regulation of macrophage properties. Gfi-lb is required for both erythroid and megakaryocytic differentiation, resembling in some aspects of GATA-1 deficiency. The overall goal of this proposal is to use a combined genetic and biochemical approach to link the Gfifactors to specific regulatory networks and pathways within hematopoietic stem cells (HSCs) and their progeny. Aim 1 focuses on genetic dissection of functions of the Gfiproteins in hematopoiesis. This will involved a detailed structure-function analysis of Gfi-1 and Gf-lb using rescue of gene targeted cells or mice, assessment of interchangeability of these factors through targeted gene knock-ins in mice, evaluation of the role of a novel isoform of Gfi-1 b (designated Gfi-lbL), and determination of the effects of Gfi-1, Gfi-lb, or combined deficiency on HSC competitive repopulation. Aim 2 focuses on biochemical approaches to the role of Gfi-proteins in hematopoietic cells. A method for in vivo biotinylation of expressed proteins will be used to facilitate efficient purification of proteins associating with Gfi-1 in myeloid cells and with Gfi-lb in
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erythroid and megakaryocytic cells. Gfi-associated proteins will be identified by massspectrometry microsequencing. Candidate interacting proteins will be further validated by coimmunoprecipitation assays and permit the Gfi-proteins to be placed within known regulatory pathways. In a second approach direct target genes of the Gfiproteins will be sought by chromatin-purification from cells expressing biotin-tagged Gfi-proteins. Candidate target DNA regions will be identified by sequencing and will be validated by conventional chromatin-immunoprecipitation assays. The significance of target genes will be further assessed using gene targeted cells and mice. This research program should elucidate how Gfi-proteins control hematopoietic differentiation and how their activation contributes to oncogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLYCOLIPID-SPECIFIC T LYMPHOCYTES Principal Investigator & Institution: Bendelac, Albert S.; Professor; Princeton University 4 New South Building Princeton, Nj 085440036 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Glycosylceramides perform important immunological functions as T cell antigens presented by CD1, a family of lipid-binding MHC-like molecules. For example, alphaGalactosylCeramides (alphaGC) specifically activate regulatory NKT cells which modulate, through the release of either Th1 or Th2 cytokines, various disease conditions, and other glycosylceramides may elicit adaptive T cell responses involved in Multiple Sclerosis. Thus, the program project uses glycosylceramides as a prime model antigen family to explore fundamental issues of glycolipid antigen presentation by CD1 molecules with potential clinical applications. The project brings together several new tools and methodologies developed in a multidisciplinary collaboration. Dr. Savage (Project #1) is generating an extended set of synthetic glycolipids modeled around alphaGC whose physical and structural interactions with CD1d and TCR are studied by Dr. Teyton (Project #2), and which we will use in this proposal to systematically explore, in the mouse system, antigen presentation by CD1d and the corresponding TCR repertoire and T cell functions. The specific aims are 1) To study T cell recognition of glycosylceramides in vivo using CD1d tetramer technology, and compare their adjuvant effects; 2) To study the Th1 vs Th2 modulatory properties of selected alphaGC variants in IDDM, EAE and rejection of liver metastasis; 3) To study how glycosylceramide structure dictates intracellular trafficking and access to endosomal compartments, using fluorochrome and radio-labeled glycolipids and developing new methodologies for the detection and imaging of CD1d-alphaGC complexes. Because glycolipids do not mutate and CD1 molecules are highly conserved, these basic studies in mice lay the foundations for the development of universal lipid-based vaccines as well as the rational design of glycosylceramide adjuvants which can modulate autoimmunity, cancer and infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GONADOTROPIN ACTION Principal Investigator & Institution: Moyle, William R.; Associate Professor; Ob, Gyn and Reproductive Scis; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2002; Project Start 01-AUG-1983; Project End 31-MAR-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Biotin
Project Title: HIGH THROUGHPUT FTICR FOR MOLECULAR ANALYSIS OF CANCER Principal Investigator & Institution: Smith, Richard D.; Battelle Fellow, Chief Scientist; Battelle Pacific Northwest Laboratories Box 999, 902 Battelle Blvd Richland, Wa 99352 Timing: Fiscal Year 2002; Project Start 16-JUN-2000; Project End 31-MAY-2004 Summary: In this four year two phase (R21/R33) project we will integrate and apply new approaches for obtaining broad systems level views of protein expression in cancer research. The overall approach will advance the study of proteomes by more rapidly identifying proteins, precisely measuring the relative abundances for all detected proteins, and providing much greater sensitivity than existing methodologies. Our approach will utilize proteome-wide stable isotope and biotin labeling of cysteinecontaining polypeptides combined with new approaches that use ultra-high sensitivity Fourier transform ion cyclotron resonance mass spectrometry. The approach will be at least 2 to 3 orders of magnitude more sensitive than existing 2-D PAGE methodologies and able to rapidly identify and measure relative expression levels for thousands of proteins in a single analysis. Phase 1 of this project will integrate and provide an initial demonstration of methods that include the sample processing for mouse B16 melanoma cells from culture, validate the use of new accurate mass tag and multiplexed-MS/MS methods for protein identification, and demonstrate the precise determination of relative protein abundances for all detected proteins from B16 and B16BL6 cell populations. Phase 2 will involve the pilot application of the technology to the study of proteome changes that occur as cells progress from low or nonmetastatic states, to a highly invasive and metastatic phenotype, using the B16 melanoma system as a model. The technology to be applied will enable ultra-sensitive (attomole level, and anticipated to be better) proteome-wide precise profiling of proteins from cells maintained in culture and from tissues (obtained by micro-dissection). The results will provide an abundance of new information on protein expression, and enable precise measurements of differences in relative protein expression levels as a function of cell type, developmental stage, metastasis, etc. A product of this research will be the first application of a high throughput technology for obtaining precise proteome displays that may be expected to illuminate the complex mechanisms and pathways relevant to cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV ASSOCIATED NEPHROPATHY IN DRUG ADDICTS Principal Investigator & Institution: Singhal, Pravin C.; Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's Abstract) The goal of the present proposal is to determine the role of HIV and illicit drugs such as opiates and cocaine in the development of renal injury which manifests itself as focal glomerulosclerosis (FGS) and tubulointerstitial lesions (TIL). We hypothesize that HIV-I in combination with the drugs interacts with monocytes and tubular cells (TC) and mesangial cells (MC) to induce TIL and expansion of the mesangium (precursor of FGS). Tubulo-interstitial lesions, a unique feature of HIV-associated renal injury, set the pace of the progression of renal failure. To examine the role of HIV-I and drugs in both glomerular and interstitial lesions we plan to 1) study the effect of HIV and drugs on the migration of macrophages (Mphi) into the interstitium and mesangium 2) determine the effect of HIV-l/drugs and Mphi interaction products on MC proliferation and matrix accumulation, 3) examine the effect
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of HIV-1 and drugs on the migrated Mphi and proliferated MC, and 4) study the effect of HIV-l/drugs and tubular cell interaction products on kidney fibroblast (KF) proliferation/apoptosis and matrix accumulation. Transmigration of Mphi across the endothelial cell layer will be determined as well as across a gelatin coated filter. Thymidine incorporation studies will be used to evaluate MC/KF proliferation. Western blots will be used to measure the laminin, fibronectin, proteoglycan and collagen components of matrix and Northern blots to measure mRNA expression for growth/cell death related genes and matrix components. A biotin-avidin assay and zymography will be used in the measurement of gelatinolytic and stromelysin activity. To examine the effect of HIV-1 gene expression, studies for cell proliferation and matrix synthesis will be carried out on MC derived from mice transgenic for HIV-I genes. In addition, these mice will be treated with drugs and acceleration of renal cortical and medullary mRNA expression of matrix components and cytokines will be evaluated. The hypothesis for the role of HIV and drugs in the development of renal injury will be tested based on our preliminary findings of increased MC/KF proliferation, and matrix accumulation when HIV-I proteins, HIV-1 protein-Mphi/TC interaction products are added to MC/KF in culture. Moreover, our results show that HIV and MC secretory/gpl20 and TC products enhance the migration of Mphi into the interstitium and mesangium. We believe that tubulointerstitial lesions determine the accelerated course of renal failure in drug addicts with HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF CASPASE SUBSTRATES FROM HUMAN PROTEOME Principal Investigator & Institution: Liu, Rihe; Medicinal Chemistry and Natural Products; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): This proposal is directed at scanning the human proteome to identify the downstream targets of caspase-2, -3 and -8 using a novel technique called mRNA display. Specifically, human proteome domain libraries displayed on their own mRNAs are generated and immobilized on the solid surface via the biotin residue specifically introduced near the N-terminus of each protein. Upon incubation with a purified caspase of interest, protein sequences that are specifically cleaved by the caspase are released and enriched, with the intact mRNA still covalently attached to the C terminus of each cleaved protein fragment. The selected protein sequences are then regenerated for iterative round of selection, by PCR amplification followed by in vitro transcription/translation, until the pool is dominated by sequences whose protein portions can be cleaved by the caspase. The identity of each protein is readily determined from its mRNA, by sequencing or cDNA microarray. To analyze the proteolysis of selected proteins by the caspase, free protein fragments and full-length proteins are transcribed/translated in vitro and incubated with the purified caspase of interest in the presence or absence of a specific inhibitor; and/or with cell-free extracts prepared from nonapoptotic and apoptotic cells. Such confirmed potential caspase downstream targets will be characterized to determine their cleavage sites using different approaches, including a focused mRNA displayed protein domain library generated by randomly priming the selected cDNA. Potential novel caspase substrates that have been demonstrated in vitro will be further analyzed in vivo, by western analysis of the potential caspase substrates in lysates from apoptotic cells. The specificity of their proteolysis will be determined by in vivo inhibitor studies. The biological
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Biotin
significance of each confirmed novel caspase substrate will be studied by correlating the extent of its specific proteolysis with the degree of cell death and with the proteolysis of other important caspase substrates. The effect of over expression of the proteins on apoptosis will also be addressed. The proposed research expected to allow a systematic examination and identification of the downstream targets of caspase-2, -3 and -8 on a proteome-wide scale. It will have significant implications in understanding the molecular mechanisms that govern the caspase-induced cell death, whose malfunction or dysregulation may result in cancer, neurodegenerative diseases, or other pathological conditions. The simplicity and high throughput of the methodology involved will make the approach broadly applicable to rapid scan the human proteome for downstream targets of any other caspases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF IMMUNOPHILLINS, & CLIENT PROTEINS
HSP90
COCHAPERONES,
Principal Investigator & Institution: Blagg, Brian Sj.; University of Kansas Lawrence Youngberg Hall Lawrence, Ks 660457563 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The 90 kDa heat shock proteins (Hsp90) belong to a family of chaperones that regulate intracellular functions and are required for the refolding of denatured proteins following heat shock as well as the conformational maturation of a large number of key proteins involved in cellular processes. This proposal outlines a novel proteomics approach toward the identification of Hsp90 client proteins, cochaperones, immunophilins, and multiprotein complexes that fold nascent polypeptides. Geldanamycin derivatives will be synthesized to contain both photolabile and nonphotolabile biotin linkers, which are expected to bind to the N-terminal ATP binding region of Hsp90 and stabilize the complex association of Hsp90, client proteins, cochaperones, and immunophilins. In the presence of ubiquitination and protease inhibitors, these Hsp90/biotinylated GDA complexes will be removed from crude cellular lysate and the multiprotein components analyzed. The identification of proteins and multiprotein complexes that are bound to Hspg0 will provide insight into the role Hsp90 plays in the maturation of regulatory pathways by the identification of Hsp90 associated proteins and could provide additional targets for cancer chemotherapy. The identification of Hsp90 client proteins will provide evidence for the rational design of future inhibitors that are selective against individual client proteins and help determine the ramifications of inhibition of the entire Hsp90 process. A derivative of geldanamycin (17-AAG) has entered clinical trials, however, it is unlikely to proceed to phase II studies due to cytotoxicity unrelated to the inhibition of Hsp90. Using the multicomponent assay described in this proposal, it is possible to identify proteins other than Hsp90 to which geldanamycin binds, providing additional controls for the development of future Hsp90 inhibitors. Using similar techniques, Hsp90 dependent proteins from various cancer cell lines will be profiled. Protein profiling of Hsp90 dependent proteins will provide additional insight into the identification of proteins that are under or overexpressed in different cancer cell lines for future applications of Hsp90 inhibition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF SUBUNIT INTERFACES IN PROTEIN COMPLEX Principal Investigator & Institution: Prevelige, Peter E.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294
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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The objective of this proposal is to develop a general methodology for the rapid identification of intersubunit interfaces in protein complexes, and utilize it to identify the subunit/subunit interfaces in immature and mature HIV-1 capsids, The strategy will be to synthesize a family of biotin-tagged chemical crosslinkers with both specific and non-specific cross-linking activity and use them as distance constraints to position subunits of known atomic structure (in this case the structural proteins of HIV) relative to one another in space, To achieve the necessary structural resolution the cross-linked amino acid residue pairs will be identified by mass spectrometry. This project extends the parent grant (AI44626) whose mission is to utilize hydrogen/deuterium exchange studies to identify intersubunit interfaces and dynamic motions in HIV capsids. The novel component of this proposal is the synthesis of biotin tagged cross-linkers, which can be rapidly purified using strepavidin affinity techniques coupled with mass spectrometry for identification of the cross-linked peptides. Such cross-linkers are not commercially available. Our preliminary data indicates that while the cross-linking data can be used to pack subunits, its widespread applicability is limited by the inherent difficulty of detecting a small number of cross-linked peptides against a background of a large number of uncross-linked peptides. Biotin tagged crosslinkers can be rapidly purified from the complex digests and analyzed by mass spectrometry resulting in increases in sensitivity and throughput. As a result the technique will become a generally applicable tool for merging data from the structural genomics and proteomics initiatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMAGING MALIGNANT MELANOMA WITH RADIOLABELED ALPHA-MSH PEPTIDE ANALOGS Principal Investigator & Institution: Quinn, Thomas P.; Assistant Professor; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (Revised Abstract) (provided by applicant): This application outlines a research effort to develop and evaluate radiolabeled peptides for malignant melanoma imaging. Malignant melanoma is a serious public health problem due to an increase in its incidence and resistance to conventional chemotherapeutics and external beam radiation therapy. Early detection is critical for proper therapeutic management. There is a clear need to develop new and efficacious imaging and therapeutic agents. Our laboratory has developed a new class of metal-cyclized peptide (CCMSH) that target the a-MSH receptor present on melanoma cells. The CCMSH peptides will be radiolabeled with 99mTc, 111In for SPECT and 64Cu for PET imaging of melanoma in murine and human melanoma mouse models. Mice bearing solid tumors and metastatic melanoma in the lungs will be imaged at various times during the course of their disease to determine the detection sensitivity and specificity of the radiolabeled peptides. Micro SPECT and micro PET imaging studies will also be compared to determine the optimal combination of peptide, radionuclide and detection modality for melanoma imaging. The CCMSH imaging agents are envisioned to be part of a matched pair strategy for melanoma imaging and therapy in which the same melanoma targeting vector (CCMSH) can be radiolabeled with radioisotopes that possess imaging or therapeutic properties. We also plan to employ bacteriophage (phage) display technology to discover new melanoma targeting vectors. The random peptide libraries, displaying 5150 peptides per particle, will be selected in human melanoma bearing mice for tumor targeting peptides. In vivo selection strategy should closely simulate the complex
32
Biotin
targeting environment an imaging agent encounters thus allowing us to select superior melanoma avid phage. We propose to use the tumor avid phage particles themselves as targeting agents in a pretarget approach. The tumor avid phage will be conjugated with <10 copies of Neutravidin per particle. Neutravidin phage will be injected into tumor bearing mice and allowed to localize to the tumor or clear the body over a period of day(s). Indium-111 labeled DTPA-biotin will be injected intravenously and the animals will be imaged over a period of several hours. Pretarget phage imaging will allow us to take advantage of the power of in vivo selection with polyvalent peptide display while not suffering the partitioning consequences of a large radiolabeled molecule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO HYDRATION CHANGES IN HEMOGLOBIN SS AND SC CELLS Principal Investigator & Institution: Joiner, Clinton H.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 11-JUL-2003; Project End 31-MAR-2008 Summary: To develop effective treatment strategies for sickle cell disease, a clear understanding of cellular pathophysiology is required. After entering the circulation, sickle cells experience a number of changes and selection processes that profoundly influence their propensity to sickle and their survival characteristics. This proposal is focused on understanding these time-dependent changes. In vivo studies will track a small volume of highly purified light or dense sickle cells in the circulation, utilizing a biotin label. This method, unique to our laboratory, offers a cell-by-cell analysis of multiple cellular properties during in vivo cell aging. One of these properties, hydration state, has been recognized to be of paramount importance. It now appears that a onedirectional dehydration model is not adequate, and that sickle cells eventually become rehydrated and have high sodium content, perhaps secondary to severe membrane damage. A preliminary biotin label study has demonstrated that these sodium loaded cells have an extremely short in vivo survival. Taken together with their numbers in the circulation, these data strongly support an important role for these cells as a terminal cellular state. The proposed studies will include examinations of the mechanism of formation and survival characteristics of these older, hydrated cells. A mechanistic model of sickle cell rehydration, based on preliminary studies with the transport inhibitors DIDS and bumetanide, will be tested in the proposed studies. Related experiments will examine the remarkably high level of phosphatidylserine (PS) externalization that preliminary studies demonstrated in sickle cells that were rehydrated in vitro. In vivo and in vitro studies will evaluate both the low level PS exposure that is present in very young erythroid cells, both sickle and nonsickle, and the high level exposure that appears to develop as sickle cells age and become dehydrated. Patients with SC and CC disease offer an important and informative counterpoint to homozygous sickle cell disease. The dehydration kinetics and survival characteristics of SC and CC cells will be explored using established and newly developed experimental approaches. This will allow a comparison to similar investigations with SS cells, and lead to a better understanding of similarities and differences in the dehydration mechanisms for these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INACTIVATION, STRUCTURE, AND MECHANISM OF MAO Principal Investigator & Institution: Silverman, Richard B.; Charles Deering Mccormick Professor; Chemistry; Northwestern University 633 Clark Street Evanston, Il 60208
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Timing: Fiscal Year 2002; Project Start 01-APR-1983; Project End 31-MAR-2003 Summary: Monoamines oxidase (MAO) is one of the enzymes responsible for the catabolism of various biogenic individuals that the concentration of various biogenic amines is diminished. Consequently, compounds that inhibit Or inactivate MAO A, the isozyme that selectively degrades norepinephrine and serotonin, exhibit antidepressant activity. Because of the importance Of maintaining a high concentration of dopamine in the brains of those afflicted with Parkinson disease, compounds that inactivate MAO B, the isozyme that degrades dopamine, are used in the treatment of Parkinson's disease. The specific aims for this project period are (i) to design new inactivators for MAO and elucidate the inactivation mechanisms of these compounds; (2) to further investigate the mechanism of MAO; and (3) to identify, at least, some of the residues in the active site of MAO. The new inactivators include 4-methylthiobenzyl amine, 4-substituteddihydropyridines, N-(2- methylenecyclopropyl)benzylamine, and a series of new heterocyclic potential inactivators of MAO. Mechanistic information will be obtained with the use of pyridine N-oxides as potential intramolecular radical traps, and by investigating the possible involvement of an active site disulfide in MAO-catalyzed oxidations. Active site structural information will be obtained by several approaches: with NMR studies of the active site labeled with 1-phenylcyclopropylamine and tranylcypromine; with classical peptide mapping following inactivation by several mechanism-based inactivators; with polymer-supported enzyme inactivation to obtain active site residue information more efficiently; with biotin- inactivator enzyme inactivation, again to gain active site residue information more quickly; by investigating the structure of the modified flavin using NMR and mass spectral techniques after inactivation of a new fungal monoamine oxidase, MAO N; by utilizing the structural information from MAO N to elucidate the modified flavin structures after inactivation of MAO B; and with an attempted crystal structure of MAO B. We also will investigate the stereoselectivity of ring cleavage of 1-phenylcyclobutylamine and determine the potential stereoselectivity of MAO-catalyzed oxidations in organic solvents and the use of MAO in catalyzing the oxidation of hydrophobic molecules in organic solvents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLAMMATORY CELLS AND MEDIATORS IN EARLY STAGES OF ALZHIEMER'S DISEASE Principal Investigator & Institution: Troncoso, Juan C.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: (Adapted from the application) Neuropathological examinations of older control subjects and cases of Alzheimer's disease (AD) from the cohorts of the Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer?s Disease Research Center (ADRC) cohorts has revealed that the lesions of AD precede the onset of dementia by many years, and perhaps decades, and that the onset of cognitive decline is temporally related to the appearance of microglial activation in senile plaques. These preliminary observations, in concert with reports that anti-inflammatory drugs reduce the risk and rate of progression of AD, suggest that inflammation plays a significant role in the pathogenesis of AD. Moreover, neuropathological studies have shown activation of inflammatory cells, complement, and cytokines in senile plaques in AD. However, previous studies have only examined brains in advanced stages of AD. In Project 4, they propose to examine the early development of AD lesions in the brain, focusing on the activation of astrocytes and microglia, perhaps in response to AB deposition, and the production of complement factors and cytokines capable of amplifying an inflammatory
34
Biotin
reaction and damaging neurons and synapses. In Specific Aim 1, they will examine the relationships between microglial activation and cortical volume, number of neurons in hippocampus and ERC, and changes in cognition. Specific Aim 2 focuses on the activation of astrocytes and their production of complement factors and cytokines (interleukin-6 [IL-6], granulocyte macrophage colony-stimulating factor [GM-CSF], and monocyte chemoattractant protein [MCP-1]) that may attract and activate microglia in senile plaques. Specific Aim 3 examines the hypotheses that the expression of microglial cytokines (IL-1a, IL-1 B, TNF-a) correlates with neuronal and synaptic degeneration in AD as measured by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) of neurons and levels of synaptophysin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF IGF MEDIATED TUMORIGENESIS Principal Investigator & Institution: Rosenzweig, Steven A.; Professor; Pharmacology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The insulin-like growth factor 1 (IGF-1 receptor (IGF-1R) is an essential regulator of cell growth and transformation. IGF-1 and IGF-2, via the IGF-1R, are potent breast cancer cell mitogens that promote the tumorigenic potential of cancer cells. The objective of this proposal is to develop reagents that block IGF-1R signaling. The insulinlike growth factor binding proteins (IGFBPs) bind IGF-1 and IGF-2 with higher affinities than the IGF-1R and serve to both protect the IGFs from degradation and reduce their delivery to the IGF-1R. The hypothesis of the proposal is that blockade of IGF-1R activity can be accomplished by developing IGF antagonists based on the structure of the IGF binding domain on the IGFBPs. The goal of Aim 1 is to define the structure of the IGF-binding domain on rhIGFBP-2 using photoaffinity labeling and mass spectrometric analyses. To this end, IGF-1 derivatized with photactivatable groups within its IGFBP-binding domain will be synthesized. This will allow the precise identification of the sites of interaction between rhIGFBP-2 and IGF-1. Based on these analyses, deletion, truncation and site-directed mutants of IGFBP-2 will be generated and tested for IGF binding activity. Aim 2 will characterize the structure and function of a 15.8 kDa fragment of IGFBP-2. The goal of Aim 3 is to examine the mechanism responsible for IGFBPP-2 inhibition of IGF action. The goal of Aim 4 is to employ phage display to screen libraries for peptides having a high affinity for the IGFBP-binding domain on IGF-1 as an alternative means of designing IGF antagonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERNAL ENVIRONMENT OF THE DEVELOPING BRAIN Principal Investigator & Institution: Saunders, Norman R.; University of Melbourne Parkville 3052, Australia Parkville, Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The brain develops in a local (internal) environment that is distinct from the rest of the embryo, but is also different from the adult. The composition of the fluids (brain extracellular fluid, ECF and cerebrospinal fluid, CSF) that form the internal environment of brain is controlled by mechanisms referred to collectively as "the blood-brain barrier". Recent work of the Pl's group suggests the route of entry from blood to brain via the CSF in the developing brain may be more important than a direct route across blood vessels, which in immature brain are few. The long term aim is to understand the nature of mechanisms that control the composition of the
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internal environment of developing brain and to determine properties of its contribution to specific features of brain development. An additional aim is to understand effects on brain development resulting from pathophysiological disturbances to barrier mechanisms. The proposals concentrate on two aspects of control of the developing brain's internal environment, one a normal property of brain barrier mechanisms and the other, pathophysiological changes in barriers properties due to an inflammatory response:(i) Definition of permeability mechanisms and pathways between blood, CSF and brain at very early stages of development. (ii) Studies of acute & long-term effects of simulated infectious inflammatory responses (evoked by injection of lipopolysaccharide, LPS) on brain barrier permeability at different stages of development and in adults. The studies will be in S. American opossums (Monodelphis domestica); they are born at a very early stage of brain development (equivalent to 13 day fetal rats). The permeability mechanisms and pathways to be studied are to proteins and small molecular weight (mw) polar molecules. Biotin (244 Da), biotin labelled probes (eg biotin dextran mw 3000Da) and proteins (albumin & fetal protein, fetuin) will be injected intraperitoneally at different postnatal (P) ages up P65 (postweaning young adult) and their distribution in CSF and brain examined by light and electronmicrosopy. Their transfer into CSF will be quantitated and compared with results with classical but non-visualizable permeability probes (radiolabelled sucrose & inulin). Similar experiments, will study the effects of an acute or chronic inflammatory response (induced by injection of LPS for different periods) on barrier permeability at different ages. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION
INTESTINAL
VITAMIN
H
UPTAKE--MOLECULAR/CELL
Principal Investigator & Institution: Said, Hamid M.; Professor and Senior Research Career Sci; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: Studies on the molecular and cellular regulation of the intestinal absorption processes of water-soluble vitamins have been limited due in part to lack of suitable molecular probes/cell models that are needed to address these issues. This situation has begun to change in recent years with the cloning and molecular characterization of the transport systems involved in the intestinal absorption of these essential nutrients, and the availability of appropriate cell models/tools. The aims of the present proposal are to delineate the molecular and cellular mechanisms involved in the regulation of the intestinal absorption process of vitamin H, i.e., biotin, a process that has been recently shown to be also utilized by two other functionally unrelated nutrients, namely the vitamin pantothenic acid and the metabolically important antioxidant lipoate [for this reason the system involved is also being referred to now as the sodium- dependent multivitamin transport system, or SMVT]. Biotin is an essential micro-nutrient whose importance to normal health and well-being is underscored by the serious clinical abnormalities that results from its deficiency which include neurological disorders and growth retardation. Humans and other mammals can not synthesize biotin, and thus, must obtain the vitamin from exogenous sources via intestinal absorption. The mechanism of intestinal biotin absorption has been characterized by us and others and evidence was obtained indicating that the process is regulated by dietary biotin levels and by ontogeny. Very little, however, is known about the molecular and cellular mechanisms involved in this regulation. The recent cloning and molecular characterization of the intestinal biotin uptake system has assisted us in initiating studies to address these issues. In preliminary studies, we have obtained evidence that
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Biotin
suggests possible involvement of transcriptional regulatory mechanism(s) in the regulation of intestinal biotin transport by extracellular biotin levels. We have also delineated the sequence of a 4.3 kb genomic DNA that is of relevance to our effort of characterizing the 5' regulatory region of the transporter gene. Based on this background, our specific aims in this proposal are: 1) to characterize the molecular/cellular mechanism(s) involved in the regulation of the intestinal biotin absorption process by dietary (extracellular) biotin levels, 2) to clone and characterize the 5'-regulatory region of the gene of the biotin transporter SMVT, and 3) to characterize the molecular mechanism(s) involved in the ontogenic regulation of the intestinal biotin transport process. The rat will be used as the experimental animal model in these studies. Results of these investigations will provide information that are of significant physiological and nutritional importance to both adult and the developing newborn regarding the molecular and cellular regulation of the intestinal absorption process of biotin in particular, and that of pantothenic acid and lipoate in general. These results should also contribute toward our understanding of regulation of SMVT function in other tissues that have been shown to express this transport system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ISOTOPE PROTEOMICS
CODED
AFFINITY
TAGS
FOR
QUANTITATIVE
Principal Investigator & Institution: Aebersold, Ruedi H.; Professor and Co-Founder; Institute for Systems Biology 1441 N 34Th St Seattle, Wa 981038904 Timing: Fiscal Year 2002; Project Start 11-FEB-2000; Project End 31-JAN-2003 Summary: Global genome initiatives including the Human Genome Project have generated enormous amounts of information, spurned new technologies and catalyzed the emergence of a new type of biology which attempts to build biological knowledge from the global analysis of biological systems, pathways and cells. In this program we propose to develop a novel technology for the quantitative and global analysis of protein expression profiles in biological samples including biochemical and subcellular fractions, biological fluids, cells and tissues. Thus, this technology will extend the global approach to biological research to the analysis of proteins, the molecules that universally constitute the structure, function and control of biological systems. The basis of the technology is a new class of reagents we term isotope coded affinity tags. The tags which are introduced to specific functional groups in proteins post isolation serve as both, ligands for the isolation of tagged protein segments as well as a quantitative code which can be mass spectrometrically deconvoluted. The proposed program has three distinguishing features which satisfy the request for innovative technology development. First, the technology explores a new approach to quantitative protein analysis and has the potential to become the technical foundation of the emerging field of proteomics. Second, the research will be conducted by a multidisciplinary team constituted as an academic/industrial partnership. This partnership is expected to accelerate dissemination of the technology by developing, commercializing and supporting the required chemistries, instrumentation and software as mature, integrated products. Third, the research will be conducted in a unique research environment, the new Institute for Quantitative Systems Biology at the University of Washington. The structure of this institute embodies the evolution of a technology from its inception to the integration into biological research programs and to the support of large-scale applications. The Institute also provides the interdisciplinary research environment and the facilities required for the academic/industrial partnership to flourish. Once developed, such a technology will be an essential tool for biologists'
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attempts to interpret the linear information of genomes in terms of function, control and mechanisms of biological systems. Applied to cancer research the method will permit the quantitative measurement and identification of the molecules that distinguish a particular cancer cell from a normal cell. The technology will thus significantly contribute to the molecular diagnosis, the assessment of the cancer risk and prognosis, and the understanding of the molecular basis of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LATERAL FLOW ASSAY FOR ONCOGENIC STRAINS OF HPV Principal Investigator & Institution: Bazar, Leonard S.; Trevigen, Inc. 8405 Helgerman Ct Gaithersburg, Md 20877 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Trevigen/TreviMed has developed the Mismatch Identification DNA Analysis System (MIDAS) that relies on SNIPase (geneticallyoptimized DNA mismatch repair enzymes) for the detection of pathogen DNA without the need for PCR amplification. The purpose of the research outlined in this Phase I proposal is to adapt MIDAS to a lateral-flow dipstick platform. To this end, we propose the following specific aims: (1) to design and test immobilized MIDAS probes to highrisk oncogenic strains of human papilloma virus (HPV strains 16 and 18) that incorporate biotin and various haptens such as dinitrophenyl (DNP), digoxigenin (DIG), fluorescein isothiocyanate (FITC), or bromodeoxyuridine (BrdU). In the presence of HPV target DNA and SNIPase, cleavage of the probe occurs, leading to the formation of a colored band on a lateral-flow dipstick. The MIDAS probes will be optimized initially with single-stranded oligonucleotides as targets, corresponding to HPV-16 and HPV-18 DNA sequences; (2) to optimize Dipstick-MIDAS for detecting the presence of cloned HPV-16 and HPV-18 DNA, and genomic DNA derived from HPV-16 and HPV18-positive cell lines. These efforts will culminate in a rapid, sensitive, multiplexed, costeffective, and accurate assay for oncogenic strains of HPV that cause cervical cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAPPING CONTACT POINTS OF INSULIN AND ITS RECEPTOR Principal Investigator & Institution: Katsoyannis, Panayotis G.; Pharmacology/Biological Chem; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Insulin is of central importance in human health and provides a general model for studies of protein structure and recognition. How does the hormone bind to the insulin receptor? How does its three-dimensional structure change in the hormonereceptor complex? Of both basic and applied importance, these questions will be investigated by synthetic, biochemical and structural approaches. The following Specific Aims are proposed: Aim 1-Toward the Receptor-Active Structure of Insulin: Multidimensional NMR Studies of Paradoxical Analogs. Crystal structures of insulin are now appreciated to represent inactive conformers of the hormone. To deduce the receptor-active structure, we will synthesize active analogs with predicted non-native structures. Of particular interest will be comparison of analogs containing corresponding D and L amino-acid substitutions. Solutions structures will be determined by NMR. Aim 2-Mapping the Insulin Receptor by Novel Photo-Crosslinking Analogs. Contact points between insulin and the receptor will be determined by synthesis of A- and B-chain analogs containing a photoactivatable crosslinking amino
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Biotin
acid (L-para-azido-Phe). Sites of covalent attachment in the receptor will be mapped by protease digestion and direct micro sequencing. Aim 3-Mapping the Insulin-like Growth Factor I (IGF-I) Receptor. Determination of contact points between this growth factor and its receptor will be pursued by the procedures outlined in Aim 2 above, using as parent compound an IGF-I analog consisting of a two-chain molecule embodying the A domain of IGF-I and the B domain of insulin or IGF-I. The feasibility of our Aims are in each case demonstrated by preliminary results. This competing application thus offers the exciting possibility of integrating nonstandard peptide chemistry with biochemistry and biophysics to investigate fundamental aspects of insulin action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ACTIVATION & CATALYSIS IN BIOTIN SYNTHASE Principal Investigator & Institution: Jarrett, Joseph T.; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Biotin is an essential protein cofactor used in carboxylation reactions central to human metabolism including enzymes involved in fatty acid biosynthesis, gluconeogenesis, and branched-chain amino acid catabolism. The terminal step in biotin biosynthesis involves the insertion of a sulfur atom between C6 and C9 of the precursor dethiobiotin, forming the biotin thioether ring. This insertion reaction is deceptively simple yet represents an impressive feat of enzymatic catalysis, requiring the enzyme break two saturated, inactivated CH bonds in dethiobiotin prior to sulfur insertion. This reaction is catalyzed by the E. Coli BioB protein, a dimeric iron- sulfur protein, and requires the participation of adenosylmethionine (AdoMet) and reduced flavodoxin. The requirement for AdoMet and flavodoxin suggests that biotin synthase is a member of a family of enzymes that reductively cleave AdoMet to generate a 5' - deoxyadenosyl radical, which is then used to generate a protein radical or to directly abstract a hydrogen atom from the substrate. More generally, biotin synthase belongs to a class of enzymes that are able to generate and control carbon and/or sulfur radicals in order to carry out difficult biosynthetic transformations; these enzymes include the human enzymes ribonucleotide reductase and lipoic acid synthase. Several obstacles have hindered in depth studies of the mechanism of biotin thioether ring formation: (I) the sulfur- containing substrate for BioB is not known, (II) the redox requirements for thioether ring formation are not known, and (III) the role of AdoMet and flavodoxin in enzyme activation is not understood. Studies described in this proposal address these substrate, protein, and activation requirements for biotin thioether ring formation, and will lead to more detailed studies of the chemical mechanism of radical-mediated sulfur insertion. By integrating information from these studies our knowledge of other enzymes in the biotin biosynthetic pathway, reconstitution of essential components of this pathway may in the future provide a convenient and inexpensive source of biotin for nutritional, therapeutic, and industrial applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR ANALYSIS OF NERVE GROWTH FACTOR ACTION Principal Investigator & Institution: Chao, Moses V.; Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2004; Project Start 01-APR-1985; Project End 30-NOV-2008
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Summary: (provided by applicant): Neurotrophins represent an important family of polypeptide growth factors which influence the proliferation, differentiation, survival and death of neuronal and non-neuronal cells during vertebrate development They have been proposed as therapeutic agents for neurodegenerative disorders and nerve injury However, clinical applications have met with very disappointing results, in part due to difficulties of delivery and pharmacokinetics in the nervous system and unanticipated side effects We have found a way to use small molecule ligands of G protein-coupled receptors (GPCR) to activate Trk receptors in the absence of neurotrophin binding These small molecules keep neurons alive by stimulating the actions of trophic factor receptors Ligands for G protein-coupled receptors represent a novel way of stimulating neurotrophin receptor signaling, however, the mechanism of this process is unknown This grant will investigate the cell biological mechanisms that account for transactivation of neurotrophin receptors in neurons and define the contribution of receptor trafficking and transport to this process Defining the proteins that regulate neurotrophin receptor internalization, translocation and signaling is critical to our understanding of normal neuronal development and function as well as perturbations that occur in response to injury or disease. Our findings are directly relevant to the understanding and treatment of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF ALPHAVIRUS ENTRY AND EXIT Principal Investigator & Institution: Kielian, Margaret C.; Professor; Cell Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: (Adapted from Applicant's Summary): All enveloped viruses use membrane fusion to infect a cell, and must bud through a cellular membrane to produce progeny viruses. Molecular information on these processes is critical to the understanding of viral disease, the development of novel anti-viral agents, and as a model for cellular membrane fusion reactions. The well-characterized alphavirus, Semliki Forest virus (SFV), enters cells via low pH-triggered membrane fusion, and exits by budding through the cell plasma membrane. Fusion is mediated by the SFV spike protein, which undergoes a defined series of conformational changes at acid pH. A critical feature of the SFV fusion reaction is its striking dependence on the presence of cholesterol and sphingolipid in the target bilayer. Dr. Kielian has also described a novel requirement for cholesterol in the SFV exit pathway. The overall goal of this grant is to define molecular features of the entry and exit of alphaviruses from cells. Her major hypothesis is that both SFV fusion and exit involve specific interactions of the viral spike protein with cholesterol in the cell membrane. She has isolated and characterized an SFV mutant (srf3) that has strikingly more efficient fusion and exit from cholesterol-depleted cells than wt SFV. A single amino acid substitution in the E1 spike subunit, a change of proline 226 to serine, is responsible for the cholesterol-independence of both srf-3 fusion and exit. In vitro mutagenesis of this domain and isolation of new srf mutants will be used to define sequences that confer alphavirus cholesterol independence. The hypothesis is that srf-3 is less cholesterol-dependent for key E1- membrane interactions in fusion and exit. This will be tested by a sensitive new fusion assay using purified lipid components, by biochemical and immunological detection of E1 conformational changes and membrane insertion, and by cryo-electron microscopy of control and sterol-depleted virus. Dr. Kielian has developed a biochemical assay for the final steps of budding and release of cell surface spike proteins into SFV virions. This assay is based on cell surface
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biotinylation of the spike proteins and virus retrieval using streptavidin-conjugated magnetic particles. This system will be used to determine the role of cholesterol in the exit of wt SFV and srf-3, to characterize virus exit requirements in intact cells, and as the basis of experiments to reconstitute the cell surface budding of SFV in a semipermeabilized cell system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR STUDIES OF ABC TRANSPORTERS Principal Investigator & Institution: Li, Min; Associate Professor; Physiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The ATP-binding cassette (ABC) superfamily proteins are important functional transporters in both prokaryotes and eukaryotes, playing the primary roles in mediating the entry and exit of a variety of molecules, which is essential for growth and regulation. Increasing evidence has shown that the native forms of these membrane-bound proteins are highly organized macromolecular complexes where the molecular composition and functional stoichiometry confer the native biology of these proteins and are dynamically regulated.The long-term objective of the proposed research is aimed at investigating the molecular organization and function of ABC transporting by focusing on cystic fibrosis transmembrane conductance regulator (CFTR). In particular, we will focus on biochemical and functional interactions between the CFTR and its associated proteins. The proposed experiments in this application focus on a group of four previously unknown CFTR-Associated proteins (CAPs) that have been purified on the basis of high affinity association with the CFTR protein. The genes encoding these four CAPs have been isolated in our laboratory. The proposed experiments are designed to address their potential molecular and functional roles in the CFTR activities. Through a combination of proposed biochemical, cellular, molecular, and electrophysiological experiments, we wish to obtain important information about the mechanism by which CAPs interact with CFTR as well as the potential functional roles of CAPs in modulation of the CFTR activity. Cystic Fibrosis (CF) is an autosomal recessive disorder caused primarily by mutations of a membrane channel protein known as cystic fibrosis transmembrane conductance regulator (CFTR). The mutations found in CF patients cause changes of both channel activity and subcellular location of the CFTR protein. Interactions between CFTR and other structural and regulatory proteins are essential for its proper function in human. Thus, the knowledge about these various interactions is essential for the full understanding of human diseases caused by the mutated CFTR Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLYBDENUM COFACTOR--BIOSYNTHESIS AND FUNCTION Principal Investigator & Institution: Schindelin, Hermann; Biochemistry and Cell Biology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 31-JAN-2003 Summary: The molybdenum cofactor (Moco) is present in four different enzyme families which catalyze important transformations in the global carbon, sulfur and nitrogen cycles. Moco consists of a mononuclear molybdenum coordinated to the sulfur atoms of a dithiolene group which is part of a substituted pterin derivative termed molybdopterin. Enzymes containing this cofactor are found in all three phylogenetic kingdoms of life, and biosynthesis of the cofactor follows the same pathway, both in
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prokaryotes and in eukaryotes including plants and human. Moco deficiency is inherited as an autosomal recessive trait and is a severe disease in humans which manifests itself in neurological abnormalities leading to premature death in the affected individuals. The experiments outlined in this proposal address two important aspects of Moco, namely its biosynthesis and its detailed function once it has been incorporated into the target enzymes. The specific aims presented in this proposal therefore are: (i) Characterization of the early steps in Moco biosynthesis through structural studies on the enzyme MoaC. MoaC most likely either catalyzes the first step in Moco biosynthesis starting with a phosphorylated guanosine, or the second step in which A molybdopterin precursor is generated which still lacks the sulfur atoms. (ii) Crystal structure analysis of molybdopterin synthase which incorporates the sulfur atoms into a molybdopterin precursor generating molybdopterin. The small subunit of the heterodimeric molybdopterin synthase contains an unusual C-terminal thiocarboxylate which serves as the sulfur donor during catalysis. (iii) Crystal structure determination of MogA which might function as a molybdochelatase and thus would be responsible for incorporating molybdenum, which is present in the cell as molybdate, into the molybdopterin. (iv) High resolution structure analysis of the Moco-containing enzyme dimethylsulfoxide reductase including characterization of different oxidation states and complexes of the enzyme with substrates and inhibitors which will lead to a detailed characterization of the catalytic mechanism. (v) Crystal structure analysis of biotin sulfoxide reductase, which is related in sequence to dimethylsulfoxide reductase but differs in substrate specificity. Comparative studies of the two enzymes will lead to a more general understanding of the roles Moco is playing in enzymes containing this cofactor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS OF VITAMIN TRANSPORT DEFECTS Principal Investigator & Institution: Fleming, Judith C.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): SLC19A3 is a member of the vitamin transporter family that includes the reduced folate carrier, SLC 19A1 and the high-affinity thiamine transporter, SLC19A2. Members of this solute carrier sub-family are 12-membrane spanning proteins that specifically transport micronutrients such as folate (SLC19A1) or thiamine (SLC19A2 and SLC19A3). We hypothesize that SLC19A3 functions as a major portal for thiamine into the body, functioning as a major (if not the only) placental thiamine transporter. It is likely to also be a major intestinal thiamine transporter as well. Thiamine, like other vitamins, is obtained through dietary intake. Systemic (dietary) thiamine deficiency can lead to a multitude of problems including neurodegeneration, wasting, and death. This study proposes to characterize the expression pattern of SLCI9A3 RNA and protein in developing embryos and adult tissues. The functional role of thiamine delivery into tissues via SLC19A3 will be addressed using a mouse model with a targeted deletion of SLC19A3. Additionally, transgenic mouse lines in which SLC19A3 is deleted in only certain tissues will be created in order to assess the importance of thiamine to particular stages of development and to individual organ systems. These studies will provide important information concerning the contribution of thiamine in development and in normal and disease systems. The work proposed will be performed in the outstanding environment provided by Dr. Ellis Neufeld's laboratory and the Division of Hematology at Children's Hospital. Dr. Neufeld's expertise in genetics, hematology and biochemistry, as well as the close proximity of experts in mouse development and transgenic models (e.g. Drs.
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Stuart Orkin and Nancy Andrews) will have a great impact on the further development of the applicant towards an independent academic research career. The proposed project will be carried out in a superb training environment that will enhance the applicant's skill and knowledge repertoire. The types of experiments proposed, using a transgenic/knockout approach, will likely provide the applicant with several new research avenues to focus on in the future as an independent researcher, and will certainly provide the necessary preliminary data to compete for completely independent funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIPLEX ANALYSIS OF INBORN ERRORS OF METABOLISM Principal Investigator & Institution: Turecek, Frantisek; Chemistry; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-1999; Project End 31-AUG-2006 Summary: (provided by applicant): Enzyme deficiencies are the major cause of genetic diseases. In spite of recent advances in nucleic acid screening technologies that elucidate correlations between genetic alterations, protein expression, and function, it is not yet practical to diagnose individual patients by sequencing their full-length genes. Enzyme analysis of tissue or blood cells remains the preferred standard for measurements of protein function to obtain confirmation of suspected disorders. The main focus of the current proposal is to develop several rapid, generally-useful, accurate, and sensitive enzyme assays based on electrospray ionization mass spectrometry as a single instrumental platform. The strategy is to quantify enzymatic reaction velocities in cultured cell lysates by observing mass changes resulting from an enzyme action on a synthetic substrate-conjugate. Biotin is used as a molecular handle in substrateconjugates, that allows facile and selective separation of enzymatic products from complex biological mixtures by reversible capture with immobilized streptavidin or monomeric avidin, followed by release for mass spectrometric analysis. Quantitation is achieved by using biotinylated internal standards that are chemically identical to the products of enzymatic reactions, but are distinguished by different molecular mass due to the presence of stable heavy isotopes. Previous results for lysosomal storage diseases showed that this approach allows detection and quantitation of enzymatic products in as little as 2500 cells, makes it possible to analyze two or more enzymatic reactions in a single reaction mixture, and the analytical procedure is readily automated. The proposed work is aimed at developing assays for the enzymes phosphomannomutase, phosphomannoisomerase, dolichol-P mannose synthase, and GlcNAc transferase II to achieve specific diagnoses of the various forms of congenital deficiencies of glycosylation. Another complex group of disorders that will be targeted are the porphyrias that often present perplexing clinical symptoms. The results from the new assays and those developed previously for lysosomal storage diseases will be transferred from the research laboratory to clinical practice. A new technology for the detection of low-level proteins, called Visible Isotope Coded Affinity Tags (VICAT), will be developed to quantify the levels of the structural protein dystrophin, whose deficiency causes Duchenne and Becker muscular dystrophies. In addition to this disease-related application, the VICAT technology will be applicable as a general method for sensitive, specific, and absolute quantitation of cellular proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NBMPR-BINDING SITE OF THE HUMAN ES ADENOSINE TRANSPORTER Principal Investigator & Institution: Buolamwini, John K.; Associate Professor of Medicinal Chemist; Pharmaceutical Sciences; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) This is a Mentored Minority Faculty Development Award Proposal designed to provide the necessary mentoring and research activities necessary to enable the PI achieve his career goals of becoming an established independent academic investigator in the cardiovascular research and drug discovery field. The proposal responds to the timely initiative of the National Heart Lung and Blood Institute to prepare underrepresented minorities scientists as independent investigators. Cardiovascular disease is the number cause of death among the American population, afflicting 1.5 million Americans with a new or recurrent heart attack, and killing over 980,000 people every year. Minorities especially AfricanAmericans are disproportionately affected. There is definitely a need more minority researchers in the cardiovascular field especially in Mississippi, which houses a large African-American Population. This proposal seeks to provide intensive mentoring and research training for the PI who is a minority assistant professor at a predominantly white higher institution, the University of Mississippi. The overall career goals of the candidate are to acquire research capabilities in areas of experimental analysis of protein- ligand complex interactions at the molecular level using photo labeling, affinity purification and use them to structurally characterize the interaction of inhibitors with the es adenosine (nucleoside) transporter to obtain insights that will be used to design and develop more specific and potent adenosine transport inhibitors as potential cardioprotective and neuroprotective drugs. Adenosine is a physiological nucleoside that is released in ischemic conditions such as a heart attack or stroke to protect tissue injury. However, its rapid uptake by nucleoside transporters abrogates this protective action. Nucleoside transport inhibitors block adenosine uptake by cells, and therefore enhance its extracellular protective effects. The inhibition of adenosine transport has therapeutic potential in heart disease and stroke that has yet to be tapped by he design and discovery of inhibitors with the requisite pharmacological profiles. Designed compounds will be synthesized and tested as es transporter ligands and adenosine transport inhibitors by flow cytometry and radioisotope methods. The candidate will receive mentorship by established well-accomplished investigators, the primary and secondary sponsors, and a cadre of four senior faculty serving on the candidates advisory committee. Ancillary course work in advanced protein techniques, mass spectrometry and experimental design, as well as American Chemical Society techniques workshops, and our research office workshops. Biweekly research progress meetings will be held with sponsors and committee members. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NF-KAPPAB SIGNALING PATHWAY PROBED WITH NATURAL PRODUCTS Principal Investigator & Institution: Liu, Jun O.; Professor; Pharmacol & Molecular Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The transcription factor NF-kappaB plays key roles in regulating gene expression in both normal physiological processes and in diseases. It
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is required for normal embryogenesis as well as immune responses to infections. Disregulation of NF-kappaB has also been implicated in a large number of human diseases from inflammation to cancer. Although much progress has been made in the past decade on understanding the early signaling mechanisms leading to NF-kappaB activation, how NF-kappaB transmits its signal after its binding to DNA in the nucleus has only begun to attraction attention in recent years. A marine natural product named pateamine A was found to be a potent immunosuppressive agent, inhibiting the T cell receptor-stimulated transcription of interleukin-2 gene. Preliminary studies revealed that pateamine A selectively inhibits NF-kappaB signaling and to a lesser extent, that of AP-1. A systematic examination of the known steps in the NF-kappaB signaling pathway revealed that pateamine A does not affect early signaling steps up to the DNA binding by NF-kappaB. Instead, pateamine A was found to block the transactivation activity of NF-kappaB, making pateamine A a valuable probe to study the nuclear signaling mechanism of NF-kappaB. To identify the molecular targets of pateamine A, a biotin-pateamine A conjugate was synthesized, which enabled the detection, isolation and identification of two pateamine A-binding proteins. These pateamine A-binding proteins have not been previously shown to be involved in NF-kappaB regulation. The main objective of this application is to confirm the molecular interaction between these proteins and pateamine A both in vitro and in vivo and to verify the physiological relevance of these proteins as mediators of the inhibition of NF-kappaB by pateamine A. The physiological functions of these proteins in regulating nuclear signaling by NFkappaB will be investigated. As these proteins have been implicated in several cellular processes, whether pateamine A affects the other known cellular activities of the putative pateamine A-binding proteins will be investigated. Lastly, gene chip analyses will be performed to determine the specificity of pateamine A for the IkappaB-NFkappaB signaling pathway by comparing the gene expression profiles of mouse embryo fibroblasts treated with pateamine A and those derived from NF-kappaB and IkappaB kinase knockout animals. In addition, crystal and solution structures of the complexes between pateamine A and its binding proteins will be obtained to facilitate the future design and synthesis of novel and simplified pateamine A analogs as candidates for development of anticancer and immunosuppressive drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL AT1A RECEPTOR INTERACTION PATNERS Principal Investigator & Institution: Yang, Qing; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-DEC-2005 Summary: (provided by applicant):The heterotrimeric guanine nucleotide binding protein (G-protein) coupled receptors (GPCR) contain seven hydrophobic membranespanning regions. Thus, their intracellular domains consist of three loops and one carboxyl terminus. It is known that the intracellular domains, especially the short fragments near the amino- and carboxyl termini of the third intracellular loop (i3 loop) are critical for interaction with and activate of G-proteins. Recent evidence indicates that some proteins other than G-proteins, so called receptor interaction partners (RIPs), can interact with the carboxyl termini and the i3 loops of some GPCRs. Although only a minute percentage of the RIPs for some GPCRs have been examined in detail, careful studies might yield important clues to the roles of intracellular domains of GPCRs. The long-term objective of my laboratory is to identify novel signaling mechanisms of the angiotensin II subtype 1 receptor (AT1R), and eventually to develop novel therapeutics that target the interface between the receptor and its interacting proteins. The short-term
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objective of this K award proposal is to define novel signaling protein complexes that are associated with the AT1R intracellular domains, and to explore their functional significance. The initial work will focus on the identification of novel RIPs in rat aortic vascular smooth muscle cells (RASM), which interact with the carboxyl terminus (AT1aR-CT) and/or i3 loop (AT1aR-i3L) of the AT1aR. Our strategy will use glutathione S-transferase (GST) fusion proteins, "pull-down" assays and mass spectrometry. We will approach our short-term goals with two specific aims.1. To identify novel receptor interaction partners (RIPs) in RASM, which interact with AT1aR-CT and/or AT1aRi3L.2. To identify the domains of AT1aR-CT and/or AT1aR-i3L that interact with the novel RIPsThis project will provide me with the opportunity to blend my previous experience in studying GPCR protein-protein interactions with new opportunities to use mass spectrometric methods to study GPCRs. Because of the emerging importance of the proteome, successful completion of this project will provide me with a solid foundation for developing an independent and self-sustaining research program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OOLEMMAL PROTEOMICS Principal Investigator & Institution: Coonrod, Scott A.; Cell Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The objectives of this grant proposal are to identify novel oocyte plasma membrane (oolemma) proteins, investigate their role in sperm-egg interaction, and test their immunocontraceptive potential. Our laboratory has recently utilized two dimensional (2-D) polyacrylamide gel electrophoresis to begin building a mouse Oocyte Proteomic Database (OPD), with over 500 silver-stained proteins being resolved to date. Cell- surface labeling with biotin has identified a subset of approximately 50 putative egg surface proteins, the Egg Surface Index (ESI). Microsequence data from several of the surface-labeled proteins indicates that one protein is novel. Another surface labeled protein is caloreticulin and in vitro indicates that cell surface calreticulin is required for fertilization. Additionally, two surface-labeled proteins are PI-PLC sensitive and in vitro suggest that these proteins are required for sperm- egg binding and fusion. Our goal is to build on our initial progress by developing a comprehensive mouse oocyte proteomic database and identifying at least five novel surface labeled proteins. These proteins will be cloned, characterized, and expressed, and their functional roles in sperm-egg interaction will be investigated. Fertility trials will then be performed in mice to test the immunocontraceptive potential of oocyte- specific novel oolemmal proteins. The specific aims of this grant proposal are: 1) To create a comprehensive mouse Oocyte Proteomic Database(OPD) and identify a subset of surface-labeled proteins, the Egg Surface Index (ESI). 2) To obtain amino acid microsequence data from oolemma proteins using tandem mass spectroscopy. 3) To clone and sequences cDNAs representing the complete open reading frame of at least five novel oolemmal proteins. 4) To investigate the functional role of novel oolemmal proteins. 5) To evaluate the immunocontraceptive potential of oolemmal proteins in mouse fertility trials. Results from this research will advance the fields of fertilization biology and immunocontraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRETARGETED RIT TO TREAT NON-HODGKIN'S LYMPHOMA Principal Investigator & Institution: Fritzberg, Alan R.; Neorx Corporation 410 W Harrison St Seattle, Wa 98119
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Timing: Fiscal Year 2002; Project Start 15-JAN-2001; Project End 31-DEC-2002 Summary: The objective of the proposed research is to develop a therapeutic agent based on pretarget radioimmunotherapy that is superior to the current treatments of non-Hodgkin's B-cell lymphoma in terms of therapeutic efficacy and non-target organ toxicity. Fusion proteins of a single chain antibody and streptavidin (scFv/SA) will be developed that are reactive with CD2O and target in a lymphoma xenograft animal model. Two candidate scFv/SA constructs will be genetically modified (e.g., with changes to the linker region) for the purpose of improving the expression, purification, and/or biochemical characteristics. Additional fusion constructs will be generated from selection of a human Fab/phage display library on CD2O-positive peripheral blood lymphocytes. All scFv/SA candidates will be evaluated for meeting set criteria for E. coli expression level, purification yield, immunoreactivity and CD2O cell binding, biotin binding affinity, and targeting ability in a lymphoma xenograft animal model. These characteristics should be sufficient to warrant further Phase II efforts directed toward cGMP scale-up and formulation development for clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The application of radioimmunotherapy toward the treatment of non- Hodgkin's lymphoma (NHL) has been constrained by dose limiting toxicity to the radiosensitive bone marrow. Antibody pretargeting provides a method to specifically deliver significantly greater doses to tumor sites without serious toxicities. A large number of patients with NHL are candidate's for this treatment. These patients represent a sizable market opportunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LYMPHOMAS
PRETARGETING
RADIOIMMUNOTHERAPY
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Principal Investigator & Institution: Press, Oliver W.; Professor of Medicine; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-JUL-2007 Summary: (provided by the applicant): Preliminary clinical trials have demonstrated that radiolabeled anti-CD2O monoclonal antibodies can achieve remissions in 65-90 percent of lymphoma patients failing chemotherapy. However, most patients treated with conventional radiolabeled antibodies (RAb) subsequently relapse and die of recurrent lymphoma. The objective of this research proposal is to optimize radioimmunotherapy (RIT) of B cell lymphomas utilizing two-step pretargeting amplification strategies to improve the efficacy and decrease the toxicity of conventional RIT. Two separate pretargeting approaches will be investigated, one using streptavidin (SA) and radioactive biotin and the second employing molecularly engineered bispecific anti-CD20 x anti-ligand antibodies which bind covalently to radiolabeled ligands. First, we will compare the biodistributions, toxicities and efficacies of anti-CD2O, anti-CD22, and anti-DR antibody-SA conjugates pretargeted to lymphoma xenografts in an athymic mouse model, followed by radiobiotin administration. Second, we will investigate the pharmacokinetics, biodistributions, toxicities, and efficacies of 2 molecularly engineered recombinant tetravalent single chain antibody-SA fusion proteins ([scFv]4-SA) and compare them to standard synthetic antibody-SA chemical conjugates. Third, we will compare the relative merits of 4 genetically engineered SA mutant molecules with native SA for pretargeting protocols in combination with either biotin or a synthetic divalent bis-biotin targeting molecule. These streptavidin mutants will afford a unique opportunity to test the effect of SA avidity on tumor penetration as delineated in the "binding site barrier" hypothesis. Fourth, we will evaluate the pharmacokinetics, biodistributions, toxicities, and efficacies of novel molecularly designed bispecific anti-
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CD2O x anti-ligand Abs which possesses a molecularly engineered binding pocket capable of binding covalently to synthetic radiolabeled electrophilic ligands. These bispecific anti-CD2O x anti-ligand Abs will be compared directly to the SA-biotin pretargeting approach in lymphoma xenograft models. We hypothesize that the pretargeting strategies defined in this proposal will improve the tumor-to-normal organ ratios of absorbed radiation compared with conventional RIT, allowing improvement in response rates and response durations with less toxicity than is currently feasible. We hypothesize that pretargeting will eliminate the necessity of administering myeloablative doses of 131I-anti-CD20 Ab with hematopoietic stem cell rescue to achieve maximal response rates and survival rates. We anticipate rapid translation of the results of these preclinical experiments into our clinical RIT program for human Non-Hodgkin's lymphomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING FOR PROTEASES IN CELLULAR COMPARTMENTS Principal Investigator & Institution: Mason, Robert W.; Alfred I. Du Pont Hosp for Children Box 269, 1600 Rockland Rd Wilmington, De 19803 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Proteases of the endosomal/lysosomal system play important roles in a number of physiological and pathological processes, including the immune response, arthritis, bone remodeling and tumor growth. Although the enzymes are primarily lysosomal, they have been detected in endosomes, on the plasmamembrane and in extracellular fluids. The origin and activity of the non- lysosomal forms of the enzymes are not clear. The long-term objectives of this project are to develop procedures that enable the active enzymes to be identified so that they can be selectively inhibited to control their activity in pathological and physiological processes. A new method has been developed using an active-site directed, covalently binding inhibitor to target intracellular compartments. This technique has been used in one cell culture system to show that active proteases are found in both endosomes and lysosomes, but are not secreted or membrane bound. A new series of reagents will be developed to enable evaluation of the unversality of this observation. The specific aims are: 1. To determine whether newly synthesized lysosomal cysteine proteases are preferentially delivered to, and activated in endosomes. Biosynthetic pulse-chase experiments will be used in concert with a transferrin-conjugated covalently reacting peptidyl inhibitor to identify newly synthesized proteases. 2. To determine whether delivery of endocytosed proteins to protease-positive compartments occurs similarly in different cell types. A range of cell types will be examined using a protein conjugated inhibitor to identify active proteases in cells. 3. To determine whether molecules taken up by different endocytic processes are delivered to similar protease- positive compartments. A conjugation system will be developed to permit inhibitors and targeting proteins to be interchanged using biotinavidin chemistry. These studies will show which molecular forms of the lysosomal proteases are capable of degrading endocytosed proteins, enabling the generation of more specific reagents to regulate endosomal proteolysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEIN TARGETS OF ENVIRONMENTAL CHEMICALS Principal Investigator & Institution: Liebler, Daniel C.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008
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Summary: (provided by applicant): Reactive electrophiles generated by environmental agents and stresses can modify proteins and trigger adaptive cellular responses reflected by gene expression and protein functional changes. Cysteine thiol groups are thought to be key sites of important oxidative or covalent adduct modification, but the specific structural characteristics that cast proteins in sentinel roles are unknown. The overall objective of this project is to identify specific protein targets that serve as triggers for cellular stress responses. We hypothesize that specific structural features allow some alkylation sensitive proteins to act as "sensor-triggers" that readily react with electrophiles and that adduction alters critical protein-protein interactions, thus causing changes in kinase signaling and transcription factor regulation. We will use new proteomics liquid chromatography-tandem mass spectrometry (LC-MS-MS) tools and approaches to study the mechanisms by which protein modifications alter key proteinprotein interactions that regulate stress responses. The specific aims of the proposed research are: 1) To identify protein classes, sequence motifs and domain structures that are targets for thiol-reactive electrophiles in human cells. Biotin-linked electrophiles will be used to combine affinity enrichment and new LC-MS-MS approaches to identify modified proteins and map the adducts to specific sequences. Different thiol-reactive electrophile chemistries will be used to establish the generality of the targets identified. Bioinformatics tools will be used to associate adducted sequences with specific domain structures and motifs. 2) To validate specific proteins as targets for thiol-reactive electrophiles in intact cells. Proteins identified as targets for biotin-linked electrophiles in Specific Aim 1 will be evaluated as targets for model electrophiles that correspond to their biotin-linked counterparts in cell models. 3) To characterize the effects of protein adduction on selected protein enzymatic activities and on selected protein-protein interactions in reconstituted systems in vitro. Quantitative proteomics methods will be applied to compare adduction with changes in target activities and protein-protein interactions in a parallel in vitro model. These studies will lay the groundwork for applying molecular target analysis to proteomes in toxicology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOME-WIDE CHARACTERIZATION OF PHOSPHOPROTEINS Principal Investigator & Institution: Morrison, Richard S.; Professor; Neurological Surgery; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Due to the importance of reversible phosphorylation in virtually all aspects of cell function and development, there exists a need to develop better methods to identify and quantify changes in the phosphorylation states of proteins on a proteome-wide level. In this R21 project, we will develop and apply new approaches, termed phosphopeptide isotope coded affinity tags (PhIAT), for obtaining proteome-wide identification and precise measurements of differences in the phosphorylation states of the proteins extracted from p53+/+ mouse cortical neurons. Our approach will utilize proteome-wide stable isotope and biotin labeling of phosphopeptides to enable high affinity isolation of phosphopeptides. We will use datadependent tandem mass spectrometry (MS/MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR/MS) to identify phosphorylated peptides that can function as accurate phosphopeptide mass tags (APMTs) to uniquely identify phosphorylated proteins. The approach will provide for high affinity isolation of phosphopeptides, be at least 3 orders of magnitude more sensitive than existing 2-D PAGE methodologies, and be able to rapidly identify and measure relative phosphorylation states for thousands of proteins in a single analysis. We will apply this
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technology to quantify differences in the relative phosphorylation state of proteins from p53+/+ and p53-/- cortical neurons treated with an apoptotic stimulus. The later phase of this project will develop methods that concomitantly combine PhIAT and ICAT labeling to identify proteins in glutamate or camptothecin treated p53+/+ cortical neurons that undergo changes in either their phosphorylation state or relative abundance compared to non-treated cells. By combining the PhIAT and ICAT strategies on treated p53+/+ neurons, we will be able to identify proteins that undergo a change in phosphorylation without a corresponding change in expression, or vice versa. The development of this capability will ultimately provide the broadest present proteome coverage since changes in protein abundance, as well as changes in protein phosphorylation states will be identifiable in a single experiment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOMIC STUDY OF MEGAKARYOCYTE TRANSCRIPTIONAL CONTROL Principal Investigator & Institution: Cantor, Alan B.; Leader, Biostatistics and Informatics Co; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Megakaryocytes are large polyploid bone marrow cells that play essential roles in hemostasis through the generation of platelets. Disorders of megakaryocyte proliferation and development, including megakaryoblastic leukemia, myelofibrosis, essential thrombocythemia, and megakaryoblastic thrombocytopenia are associated with high morbidity and mortality in humans. While much is known about platelet biology and the cytokine regulation of megakaryopoiesis, the transcriptional regulation of megakaryocyte development and growth is incompletely understood. Prior work has shown that the zinc finger transcription factor GATA-1 plays an essential role in both of these processes. Deficiency of GATA-1 leads to marked hyperproliferation and impaired maturation of megakaryocytes, and causes progressive myelofibrosis in mice. Mutations that result in an amino terminal truncation of GATA-1 are highly associated with megakaryoblastic leukemia in patients with Down syndrome. Preliminary studies using gel filtration chromatography indicate that GATA-1 participates in at least two stable multiprotein complexes of about 360 and 230 kDa in the L8057 murine megakaryocytic cell line (molecular mass of GATA-1 alone is 48 kDa). This proposal utilizes a proteomic approach to identify the components of these complexes and test the following hypotheses: (1) the formation of stable multiprotein complexes containing GATA-1 is functionally important in controlling megakaryocytespecific gene expression and growth control; (2) the composition of GATA-1 containing complexes changes during megakaryocyte differentiation, (3) distinct GATA-1 containing complexes exist in megakaryocyte versus erythroid cells, and (4) amino terminal truncation mutations of GATA-1 associated with megakaryoblastic leukemia result in altered multiprotein complex formation and/or activity. A novel method employing metabolic biotin tagging followed by avidin affinity chromatography will be used to isolate GATA-1 containing complexes. Components will be identified by LC/MS/MS mass spectrometry and database search. Results will be validated by coimmunoprecipitation and gel shift assays in primary megakaryocytes. Finally, the functional significance of identified components will be assessed by stable RNAi gene silencing in induced L8057 cells. The results of this study should provide new insights into the transcriptional regulation of megakaryopoiesis, and possibly new therapeutic targets for disorders of megakaryocyte proliferation and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGENERATION OF 11-CIS-RETINAL IN THE RETINA Principal Investigator & Institution: Rando, Robert R.; Gustavus Adolphus Pfeiffer Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-1982; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract): The vertebrate visual cycle is comprised of biochemical reactions involved in processing all-trans retinal produced by the photoisomerisation of 11-cis retinal in rhodopsin. The visual cycle is essential for vision and visual adaptation. The goal of this project is to characterize on a molecular level essential components of the visual cycle and to learn how the cycle is regulated. Two of the key reactions in the visual cycle are catalyzed by the retinal pigment epithelium membrane bound enzymes, lecithin retinol acyl transferase (LRAT)and the isomerohydrolase. LRAT transfers an acyl group from lecithin to vitamin A to generate all-trans retinyl esters and the omerohydrolase processes the esters to produce 11-cis retinol. Both enzymes are essential for vision. An understanding of LRAT at the molecular level is of major interest in this grant proposal. LRAT has a unique sequence which does not reveal the mechanistic class to which it belongs. Biochemical studies including chemical mapping studies using the novel technique of biotin affinity labeling and site-specific mutagenic studies are proposed to both map elements of the active-site structure of LRAT and define its molecular mechanism of action. Chemical mapping studies are also proposed to begin to elucidate the structure of LRAT in the membrane and to reveal nearest neighbor proteins in RPE membranes. One of the LRAT associated proteins may be the isomerohydrolase. Identification and characterization of isomerohydrolase is another important aspect of this proposal. Approaches to the identification of this enzyme system will involve both exploiting interactions with LRAT to either affinity purify or cross-link isomerohydrolase and photoaffinity labeling approaches to label the enzyme. When isomerohydrolase is identified it will be coned sequenced and expressed in LRAT transfected HEK cells. The structure, mechanism of action and regulation of the isomerohydrolase will be explored as will possible relationships to diseases of vision caused by mutations in the enzyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF MEMBRANE EXCITABILITY Principal Investigator & Institution: Beam, Kurt G.; Professor; Physiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JUL-2006 Summary: The long-term objective of this project is to identify the molecular interactions underlying skeletal-type excitation- contraction (EC) coupling, the process which links electrical excitation to muscular contraction. EC coupling hinges upon a functional interaction between the ryanodine receptor (RyR), a Ca2+-release channel located in the sarcoplasmic reticulum (SR), and the dihydropyridine receptor (DHPR), a voltage-gated Ca2+ channel which is located in the plasma membrane and contains alpha1S as its principal subunit. A number of experimental approaches will be used to probe the interaction between the DHPR and RyR, including the use of patch clamping, Ca2+ indicator dyes, electron microscopy and molecular biology. The proposal's first specific aim is to establish the determinants that cause DHPRs to target to junctions between the plasma membrane and sarcoplasmic reticulum. This will be accomplished by expression in dysgenic (alpha1S-null) myotubes of green fluorescent protein (GFP) tagged chimeras of alpha1S and alpha1H (a distantly related Ca2+ channel), and by a yeast two-hybrid
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screen of a muscle library using a potential targeting domains of alpha1S as baits. The second aim is to use alpha1S/alpha1H chimeras expressed in dysgenic myotubes as a means of testing whether the beta subunit of the DHPR is required for skeletal-type coupling, to determine whether the primary sequence of cytoplasmic domains outside the II-III loop are critical for coupling, and to identify the sequence(s) of alpha1S that cause DHPRs to be organized into "tetrads". The third aim is to test whether EC coupling depends upon conformational changes of the alpha1S II-III loop, which will be examined by means of introducing structural perturbations into the regions of the loop which surround the "critical domain" of the loop. One perturbation to be tested is the introduction of the biotin acceptor domain, which specifies the metabolic addition of biotin to a small number of native enzymes containing this essential cofactor. The fourth aim is to attempt to reconstitute skeletal-type coupling by expressing a minimal set of muscle proteins in a non-muscle cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPONSIVE POLYMER-ENGINEERED PROTEIN CONJUGATES Principal Investigator & Institution: Hoffman, Allan S.; Professor; Bioengineering; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-FEB-1996; Project End 31-MAR-2008 Summary: (provided by applicant): The long term objective of our research is to develop new compositions and technologies for controlling biomolecular recognition processes in the rapidly developing fields of micro- and nano-scale sensing and diagnostic devices. In the first eight years of this research program, we have developed a new approach to the control of biomolecular recognition that is based on coupling the stimulated collapse (dehydration) or expansion (rehydration) of the "smart" polymer coil with recognition events such as protein-ligand, enzyme-substrate, protein-protein and DNA hybridization reactions. In this approach, the smart polymers serve as both antennae and actuators, to sense signals and respond to them, leading to control of biorecognition events. Their characteristic sharp responses in coil size and physical properties to small changes in pH, temperature, and/or electromagnetic irradiation over narrow ranges or at specific wavelengths permits rapid and precise control of molecular events. We term this a "molecular switch". We seek here to continue the development and applications of such molecular switches with affinity proteins, ligands and enzymes, as well as to develop new strategies for releasing captured targets on command, and for "molecular matchmaking" that selectively and reversibly brings together specific, interactive molecular components in complex mixtures. The molecular engineering underlying these aims spans sophisticated polymer design and synthesis and protein and DNA engineering, and matches the functional properties of the stimuliresponsive polymers to the molecular complexities of ligand binding pockets, active sites, and receptor-ligand sequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SINGLE MOLECULE STUDIES OF ENZYME CATALYSIS Principal Investigator & Institution: Hammes, Gordon G.; Professor; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): This research is concerned with studying the dynamics of single enzyme molecules with fluorescence microscopy. The principle of the method used is to fix the active enzyme to the surface of a quartz slide and to view
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the trajectory (time course) of the enzyme during the course of ligand binding and/or catalysis. The enzyme is labeled with a fluorescent tag that monitors events on the enzyme through changes in fluorescence. Methods are being developed for both the fluorescent labeling of the enzymes and their attachment to the quartz slide. Initially the enzyme of interest will be labeled with biotin, usually as a tag on the amino terminus of the enzyme, and attached to a slide to which avidin is tightly bound at a dilute concentration. Because biotin binds to avidin very tightly, the enzyme will become attached to the slide. The changes in fluorescence are followed either with an ICCD camera or an avalanche photodiode. Single molecule kinetics have the potential of revealing steps in the catalytic process that cannot be observed with ensemble averaged kinetics. These include direct observation of the coupling of the enzyme conformation to catalysis, monitoring the conformation of different parts of a single enzyme molecule simultaneously, and dissection of processive reactions, such as DNA synthesis, into the individual steps in the reaction. Two enzymes are being investigated, dihydrofolate reductase (DHFR) and T4 DNA polymerase. The trajectories of individual DHFR molecules reacting with methotrexate reveal a conformational change that is not seen with ensemble averaged kinetics. The binding of other ligands to DHFR is being carried out and the hydride transfer reaction is being studied with single DHFR molecules. In the case of T4 DNA polymerase, experiments are being carried out in which either the DNA template or the enzyme is attached to the quartz slide. The addition of individual bases to the growing DNA chain will be monitored and the kinetics characterized. These experiments are directed at understanding better how enzymes catalyze physiological reactions. A better understanding of enzyme mechanisms is essential for understanding the physiology of disease and the development of new drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SINGLE-MOLECULE ANALYSIS OF NUCLEOCYTOPLASMIC TRANSPORT Principal Investigator & Institution: Gelles, Jeff; Professor; Biochemistry; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Description (provided by applicant): The nuclear pore complex (NPC) mediates the specific, bi-directional transport of large protein and RNA molecules across the nuclear envelope of a eukaryotic cell. Consequently, proper NPC function is essential for a wide variety of cellular biosynthetic and regulatory processes. Small perturbations of transport function can cause disease; for example, inefficient or excess transport of a single gene regulatory factor can give rise to cancer. The goal of the proposed research is to fundamentally advance our knowledge of NPC function by using in vitro singlemolecule biophysics techniques to directly observe the NPC-mediated import of individual protein molecules bearing a nuclear localization signal and tagged with a fluorescent marker. The specific aims of the project are: 1) to identify spatially distinguishable intermediates in the transport process by tracking the nanometer-scale movement of individual, labeled substrate molecules as they travel across the nuclear envelope of isolated frog oocyte nuclei; and 2) to define a minimal kinetic mechanism for substrate transport by following the sequence of intermediates through which individual substrate molecules pass and determining the characteristic lifetimes of the intermediate states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STAGED SELF-ASSEMBLY OF FUNCTIONAL NANOSTRUCTURES Principal Investigator & Institution: Hyman, Paul L.; Principal Investigator; Nano Frames 9 Keswick St Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 13-SEP-2001; Project End 31-AUG-2003 Summary: (Applicant's abstract): This project demonstrates the feasibility of staged nanostructures assembly for the manufacture of complex one-, two-and threedimensional architectures with functional groups arranged in arbitrary, designed positions. The logic of the method is analogous to solid-phase polymer synthesis. In this case, the structure is assembled by sequential protein unit addition, one subunit at a time. By using protein units of well defined size, shape and stoichiometry, each of which may harbor a different designed functionality, construction of complex nanostructures with various potential utilities is possible. The system is based on proteins and protein constructs from the phage tail fibers of T-even bacteriophage. These proteins are: highly resilient physically and chemically; interact through very strong, non-covalent bonds; and amenable to re-engineering for the introduction of designed functionalities. The long term goal of the project is a comprehensive system for design and manufacture of polyfunctional nanostructures. There is a huge gap between the popular version of computer nanochips self-assembling by the billions from a solution of molecular components and the real, pragmatic problems of assembling complex nanodevices. The process described here is a practical implementation of nanostructure assembly that has the potential for fabrication of very low cost, complex devices and materials. PROPOSED COMMERCIAL APPLICATION: The proposed system will enable massive parallel manufacture of complex nanodevices which can be further self-assembled into higher order architectures in a hierarchic manner. Applications are in many fields in which the fabrication of smart materials from the molecular level-up are required. Some examples of potential commercial applications are in the technologies of separations, catalysis, microfluidics, light materials, non-linear optics, memory and circuitry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL ANALYSIS OF MACROMOLECULAR ASSEMBLY Principal Investigator & Institution: Frank, Joachim; Professor of Biomedical Sciences; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2003; Project Start 01-APR-1982; Project End 31-MAR-2007 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE AND FUNCTION OF ENZYMES - ROLE OF METALS Principal Investigator & Institution: Rajagopalan, Kv V.; James B. Duke Professor of Biochemistry; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-MAY-2004 Summary: Molybdopterin is the essential component of the cofactors of all mononuclear molybdenum- and tungsten containing enzymes. Most procaryotic enzymes contain dinucleotide forms of molybdopterin with GMP, AMP, CMP or IMP. The most elaborate form of the cofactor is bis(molybdopterin guanine dinucleotide)-Mo, first identified in R. sphaeroides dimethyl sulfoxide reductase which contains no other cofactor. R. sphaeroides biotin sulfoxide reductase and E. coli trimethylamine-N- oxide reductase also contain bis(MGD)-Mo as the sole cofactor. These three-enzymes have been genetically cloned and have been successfully expressed in Escherichia coli. In
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collaboration with crystallographers elsewhere the X-ray structure of DMSO reductase has been determined, and we will attempt to obtain the crystal structures of the other two enzymes as well. Our ultimate goal is to examine in detail the structure- function interrelationship in these enzymes using a variety of spectroscopic and kinetic methods and availing site-directed mutants generated from a study of the crystal structure. The mechanism by which the complex bis(MGD)-Mo cofactor is assembled is also being investigated. We have cloned and have been able to overexpress many of the E. coli enzymes involved in the biosynthesis of molybdopterin and the variant forms of the cofactor. The crystal structures of two of the proteins, MoaC and MogA have been elucidated and will be used to explore the active sites and catalytic mechanisms. The reactions of the pathway will be studied in detail. These studies are of extreme importance, since molybdenum cofactor deficiency in humans causes severe neurological problems most often leading to neonatal death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND INTERACTIONS OF MODEL BIOMEMBRANES III Principal Investigator & Institution: Israelachvili, Jacob N.; Chemical Engineering; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 01-MAY-1992; Project End 31-DEC-2002 Summary: We hypothesize that "softly supported" bilayers incorporating selectins are excellent in vitro models for Surface Force Apparatus (SFA) measurements of the 'rolling forces' between complementary surfaces expressing selectins and its ligands. Isolating the molecular features (static and dynamic forces, mobility, on and off rates, etc.) of the specific ligands and receptors that control cell-cell and cell-substrate adhesion is difficult in vivo, although necessary for determining the basic rules governing cell sorting, tissue differentiation, pathological deformations and growths, and the body's control of cell population size and location. In addition, the dynamics of specific adhesion, i.e., of receptor -ligand pairs, is essential for understanding the body's immune response and in the biomimetic construction of drug delivery systems. The specific systems to be examined include: (1) Measurement and characterization of biomolecular and biosurface interactions. The Surface Forces Apparatus (SFA), AFM, and optical microscopy will be employed to measure bilayer, membrane and specific protein (e.g., ligand-receptor) interactions of softly-supported bilayers and monolayers. Specific systems will include: (1) the dynamic interactions of P-selectin proteins with various ligands such as lipid bilayers exposing polysaccharide headgroups (selectins are an important family of adhesion and recognition proteins), (2) DNA-lipid biolayer interactions which are primarily important for DNA transfection agents such as DNAencapsulating vesicle delivery systems; (3) comparing these interactions to PEG-tethered biotin-lipids and streptavidin, this being a genetic tethered system with strong ligandreceptor bonds of varying tether length. (2) Biomimetic construction of complex structures. We plan to determine optimal methods of initiating, limiting, and controlling vesicle aggregation to produce aggregates of defined size and composition by manipulating (i) ligand-receptor stoichiometry, (ii) ligand-receptor "on- rates" through control of electrostatic or steric repulsions induced by pH, divalent ions and (iii) bilayerbilayer and vesicle-vesicle interactions through control of surface charge or polymeric steric layers, ionic strength, or divalent ions. We also will study metastable bilayer structures for use as generic encapsulating membranes. The systems will include (i) mixtures of saturated phospholipids, cholesterol and polymer lipid that form open discs, and (ii) mixtures of long and short chain phosphatidylcholines, that form bilayer
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discs at low temperatures but close to form vesicles at higher temperatures, and (iii) ethanol interdigitated bilayers of DPPC that also form temperature dependent discs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE-FUNCTION ANALYSIS OF ENZYMES Principal Investigator & Institution: Holden, Hazel M.; Professor; Institute for Enzyme Research; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUN-1997; Project End 31-MAY-2005 Summary: (Applicant's Description) The concept of substrate channeling was originally put forth to explain the manner in which reactive intermediates are transferred from one protein to another in a metabolic pathway or shuttled from one active site to another within a single enzyme. Many have regarded the phenomenon as a critical method for the regulation of metabolic pathways within the living cell. The goal of this proposal is to explore, on a structural basis, the mechanisms of actions of the following enzymatic systems known to employ substrate channeling: carbamoyl phosphate synthetase, asparagine synthetase, and acetyl CoA carboxylase. The first two enzymes utilize substrate channeling between active sites within a single polypeptide chain while in the latter protein, the event occurs between active sites positioned on different polypeptide chains. These systems were selected for study not only because they use substrate channeling in their reaction mechanisms, but also because of their biological importance. Carbamoyl phosphate synthetase is involved in the de novo synthesis of pyrimidine nucleotides which are critical for cell proliferation. The enzyme also plays a key role in both arginine biosynthesis and the urea cycle in most terrestrial vertebrates. Asparagine synthetase catalyzes the ATP-dependent conversion of aspartic acid to asparagine and has been used in chemotherapeutic protocols for treating acute lymphoblastic leukemia. Finally, acetyl CoA carboxylase catalyzes the first committed and absolutely critical step in fatty acid synthesis. For these investigations, a combination of site-directed mutagenesis experiments and x-ray crystallographic analyses will be employed in order to more fully characterize the three-dimensional architectures of these proteins, their active site geometries, catalytic mechanismd, and the relationships of these parameters to substrate channeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUBSTRATES AND INSULIN RECEPTOR ENDOCYTOSIS Principal Investigator & Institution: Najjar, Sonia M.; Associate Professor; Pharmacology and Therapeutics; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 31-JAN-2004 Summary: Impaired insulin action, or insulin resistance, is a hallmark of Non-InsulinDependent Diabetes Mellitus (NIDDM). Because insulin resistance is a major factor in the pathogenesis of NIDDM, understanding the mechanisms of insulin resistance has potential implications in identifying novel means to improve insulin sensitivity in individuals predisposed to NIDDM. Insulin binding to its receptor activates the tyrosine kinase of the receptor to cause phosphorylation of the receptor and of other substrates, such as ppl20, a plasma membrane glycoprotein in the hepatocyte. pp120 is phosphorylated on Ser503 in the intracellular domain by cAMP-dependent kinase in the absence of insulin, and this phosphorylation is required for its phosphorylation on Tyr488 by the insulin receptor kinase in response to insulin. The role of ppl20 in insulin action is not well understood. pp120 expression in cultured cells was correlated with
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increased rate of insulin clearance from the medium through a mechanism of receptormediated endocytosis, suggesting that pp120 is important in the process of insulin clearance from the portal circulation. In contrast, expression of phosphorylationdefective pp120 isoforms (truncated and the Y488F and S503A site-directed mutants) did not increase receptor-mediated insulin internalization, suggesting that the effect of p120 on insulin endocytosis depends on its phosphorylation state. Immunofluorescence and biotin-labeling studies suggested that pp120 exerts its effect by undergoing receptormediated internalization in response to insulin. Thus, it appears that pp120 takes part in a complex of proteins that target the insulin receptor to endocytosis vesicles. The complex formation between pp120, at Tyr488, and the insulin receptor, at Tyr960 of its juxtamembrane domain, appears to be mediated by intracellular proteins. We herein propose to identify these proteins. Additionally, we propose to address the role of ppl20 in the mechanism of insulin action in vivo. To this end, we have generated a transgenic mouse overexpressing a phosphorylation-defective S503A isoform of ppl20 in liver. The transgenic line will address whether expression of a phosphorylation-defective pp 120 is associated with a blunted ability to remove excess insulin from the portal circulation, causing peripheral hyperinsulinemia. Since hyperinsulinemia leads to receptor downregulation on target tissues, it is usually associated with insulin resistance. These proposed studies should provide novel insights into a potential mechanism of hyperinsulinemia, insulin resistance and diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TARGETING NEUROINFLAMMATION
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Principal Investigator & Institution: Bickel, Ulrich; Pharmaceutical Sciences; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: [Applicant's Abstract] This proposal explores a novel use of transferrin receptor mediated drug delivery. An oligonucleotide (ODNbased drug will be targeted to brain microvascular endothelial cells, with the goal to inhibit inflammatory responses in these cells. The approach could have broad applicability for diseases affecting the blood-brain barrier and the central nervous system. Here, we focus on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, to demonstrate the feasibility of this vascular targeting strategy. Crucial events in the pathogenesis of that disease affect function and integrity of the BBB. The endothelial cells forming the BBB express adhesion molecules affecting lymphocyte transmigration, and enzymes such as inducible NO-synthase and cyclooxygenase-2 contributing to inflammation. Expression of these proteins is under control of the transcription factor NF-kappaB. Therefore, preventing NF-kappaB activation could be a promising therapeutic strategy. An elegant way to inhibit a transcription factor is the cellular delivery of decoy ODNs, short double stranded ODNs containing the consensus binding sequence of that factor. Unfortunately, decoy ODNs face similar problems as related antisense approaches, namely poor permeability through cell membranes. The receptormediated endocytosis provided by the transferrin receptor system can overcome that obstacle. Here, the 8D3 antibody specific for the mouse transferring receptor will serve as the vector for delivery of a NF-kappaB decoy ODN. The polyanionic ODN will be bound in a complex by the cationic polymer polyethylenimine, and then coupled to the 8D3 antibody via an avidin-biotin bridge. Polyethylenimine is an attractive carrier for DNA due to its capacity to mediate "endosomal escape", thus enabling the ODNs to reach their cytosolic or nuclear sites of action. The Specific Aims of the project comprise
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(i) the determination of the cellular uptake and pharmacological activity of the ODN delivery system in an in vitro model with a murine brain endothelial cell line; (ii) determining the in vivo pharmacokinetics of the delivery system in normal mice; and (iii) evaluating in vivo pharmacological effects of vector-mediated ODN delivery in the mouse EAE-model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSFERRIN CONJUGATES FOR ORAL PROTEIN DRUG DELIVERY Principal Investigator & Institution: Shen, Wei-Chiang; Professor; Pharmaceutical Sciences; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: Gastrointestinal absorption appears to be the most desirable route for the administration of drugs including therapeutic peptides and proteins, because it can reduce both the inconvenience and the complications associated with injection, and increase patient compliance especially in chronic administration. However, no acceptable oral formulation is currently available for peptide and protein drugs. In this application, a novel approach, which is based on our preliminary findings of the transferrin receptor-mediated transcytosis in intestinal epithelial cells, will be explored for increasing peptide and protein absorption in the gastrointestinal tract. Our hypothesis is that there is a constitutive transcytosis of transferrin receptors from the luminal to the basolateral membranes in the gastrointestinal tract due to an alternative pathway for the membrane sorting in intestinal epithelial cells. The advantages of this approach include the specificity and the stability of transferrin, as well as the abundance of transferrin receptors in the intestinal epithelium. Transferrin conjugates of insulin and granulocyte colony stimulating factor (G-CSF) will be prepared. Both reversible and irreversible linkages for the conjugation will be investigated. In order to obtain structurally defined conjugates, transferrin with a single modification site will be produced by two different approaches; by purification using biotin-avidin affinity chromatography, and by recombinant technology to generate a mutagenized transferrin containing a single free sulfhydryl group for conjugation. Insulin-transferrin and G-CSFtransferrin conjugates will be first characterized by using biochemical and biological methods, including PAGE, immunoassays, transcytosis in human enterocyte- like Caco2 cells, and in vitro bioassays. Selected conjugates will be administered to rats or mice, both subcutaneously and orally, to measure hypoglycemic and neutrophilic activities for insulin and G-CSF, respectively. Tyrphostin 8, a specific enhancer for transferrin receptor-mediated transcytosis, will be co-administered to evaluate the increase of the transport efficiency. This proposal will provide essential information for the development of either chemically synthesized or genetically engineered proteintransferrin conjugates as safe and effective drugs that can be administered orally for the treatment of various human diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRNA LABELING OF CELLULAR EXPRESSED PROTEINS Principal Investigator & Institution: Lim, Mark J.; Ambergen, Inc. 1106 Commonwealth Ave Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-AUG-2003
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Summary: The completion of the human genome project highlights a need for highthroughput analysis of gene expression at the protein level. Proteomics involves global analysis of the entire expressed complement of the genome. The general aim of this project is to introduce a powerful method for labeling nascent proteins produced in intact cells. This novel approach, termed TRACE-PRO (tRNA Labeling of Cellular Expressed Proteins) will open new avenues for studying cellular protein expression and protein-protein interactions. During Phase I, methods will be developed to efficiently introduce specially designed tRNAs into intact cultured mammalian cells. These tRNAs, which have already been developed and successfully evaluated in prokaryotic and eukaryotic cell-free lysates by AmberGen, act to introduce detection labels and affinity linkers into newly expressed proteins. Detection labels will be evaluated for their ability to replace more conventional radioactive labels to facilitate high throughput 2-D PAGE and capillary electrophoresis modes of detection and mass spectrometric identification of the labeled nascent proteins. Affinity linkers will be evaluated for their ability to facilitate identification of interacting cellular proteins. During Phase II, TRACE-PRO will be used to profile changes in protein expression and protein-protein interactions triggered in response to external stimuli such as addition of drugs. PROPOSED COMMERCIAL APPLICATION: The development of a cell-based protein expression labeling system using fluorescent and affinity tags will result in commercial products including reagents and hardware for proteomics research. AmberGen also plans to offer an in-house protein-protein interaction services which will be marketed to the pharmaceutical industry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UNIVERSAL VECTORS FOR THE THERAPY OF CANCER Principal Investigator & Institution: Penichet, Manuel L.; Microbiology and Immunology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by Applicant) My immediate career goal is continue my research in the fields of cancer research focusing mainly in the development of new drugs for cancer therapy. To achieve this goal I propose to develop universal delivery systems that can be used to deliver DNA or cytotoxic molecules to tumor cells expressing on their surface the interleukin-2 (IL-2) or transferrin (Tf) receptor (IL-2R or Tf-R). The delivery system will be antibody fusion proteins that either have the ligand (e.g., IL-2 or Tf) covalently associated or have a variable region that recognizes a growth factor receptor (e.g., anti-TfR). The antibody fusion proteins containing IL- 2 or Tf will be specific for the hapten dansyl (DNS) and will be used for the delivery of dansylated agents. The anti-TfR antibody will be covalently fused to avidin and will be used for the delivery of biotinylated agents. To produce and characterize the delivery vehicles I propose the following specific aims: 1. Produce the recombinant antibody fusion proteins to be used as universal delivery vehicles; 2. Evaluate the ability of the Ab fusion proteins to deliver proteins or DNA to cells growing in vitro; 3. Determine the properties of the Ab fusion proteins in vivo and their ability to target and eliminate tumors in animal models. I anticipate that the vector systems will provide powerful tools for treating a wide variety of important malignancies. The universal vectors will make it easier to treat tumors with multiple anti-cancer agents and will facilitate the rapid evaluation of potential new therapeutic agents. Although initial principles will be established using IL-2R and/or TfR as targets, future universal vectors can target other tumor associated molecules. Having been trained as an M.D./Ph.D., I have a strong
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grounding in both basic and clinical science. The training that I will receive during the time of this grant will enhance both my research skills and my facility with English. This additional training is necessary if I am to assume an independent position doing research at a major university. UCLA provides an excellent, supportive environment for the proposed research. There is a large faculty with expertise in virtually every discipline. Excellent seminar series and technical training sessions are available. The University is committed to my career development and will provide resources without requiring any teaching or clinical activities. The training period will also allow me to attend national and international meetings, both expanding my expertise and my network of collaborators and colleagues. 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 “biotin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for biotin in the PubMed Central database: •
A new biotinylating system for DNA using biotin aminocaproyl hydrazide and glutaraldehyde. by Takahashi T, Arakawa H, Maeda M, Tsuji A.; 1989 Jun 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318063
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A plasmid expression system for quantitative in vivo biotinylation of thioredoxin fusion proteins in Escherichia coli. by Smith PA, Tripp BC, DiBlasio-Smith EA, Lu Z, LaVallie ER, McCoy JM.; 1998 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147411
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A protected biotin containing deoxycytidine building block for solid phase synthesis of biotinylated oligonucleotides. by Pieles U, Sproat BS, Lamm GM.; 1990 Aug 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331251
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A simple subtractive hybridization technique employing photoactivatable biotin and phenol extraction. by Sive HL, St John T.; 1988 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338969
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A structural snapshot of an intermediate on the streptavidin --biotin dissociation pathway. by Freitag S, Chu V, Penzotti JE, Klumb LA, To R, Hyre D, Le Trong I, Lybrand TP, Stenkamp RE, Stayton PS.; 1999 Jul 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17525
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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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Active Transport of Biotin in Escherichia coli K-12. by Prakash O, Eisenberg MA.; 1974 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245839
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Adsorption and biotin-streptavidin amplification in serologic tests for diagnosis of Lyme borreliosis. by Magnarelli LA, Anderson JF.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270206
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An easy method to check the efficiency of biotin end-labelling of DNA-fragments. by Holmstrom K, Rasmussen OF.; 1990 Aug 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331322
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An Embryo-Defective Mutant of Arabidopsis Disrupted in the Final Step of Biotin Synthesis. by Patton DA, Schetter AL, Franzmann LH, Nelson K, Ward ER, Meinke DW.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35095
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Application of the avidin-biotin method of gene enrichment to the isolation of long double-stranded DNA containing specific gene sequences. by Pellegrini M, Holmes DS, Manning J.; 1977 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342627
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Avidin-biotin latex agglutination assay for detection of antibodies to viral antigens. by Shekarchi IC, Fuccillo DA, Sever JL, Madden DM.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266494
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Biochemical Characterization of the Arabidopsis Biotin Synthase Reaction. The Importance of Mitochondria in Biotin Synthesis. by Picciocchi A, Douce R, Alban C.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129290
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Biological Studies with [alpha]-Dehydrobiotin. by Hanka LJ, Reineke LM, Martin DG.; 1969 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=315355
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Biosynthesis of 7,8-Diaminopelargonic Acid, a Biotin Intermediate, from 7-Keto-8Aminopelargonic Acid and S-Adenosyl--Methionine. by Eisenberg MA, Stoner GL.; 1971 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247197
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Biosynthesis of biotin from dethiobiotin by the biotin auxotroph Lactobacillus plantarum. by Bowman WC, DeMoll E.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206929
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Biosynthesis of Biotin in Microorganisms V. Control of Vitamer Production. by Birnbaum J, Pai CH, Lichstein HC.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276913
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Biosynthesis of Biotin in Microorganisms VI. Further Evidence for Desthiobiotin as a Precursor in Escherichia coli. by Pai CH, Lichstein HC.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276924
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Biosynthesis of biotin in microorganisms. VII. Effect of glucose on vitamer synthesis by thermophiles. by Papiska HR, Lichstein HC.; 1968 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252145
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Biosynthesis of Biotin: Synthesis of 7,8-Diaminopelargonic Acid in Cell-Free Extracts of Escherichia coli. by Pai CH.; 1971 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=248502
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Biotin and fluorescent labeling of RNA using T4 RNA ligase. by Richardson RW, Gumport RI.; 1983 Sep 24; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=326365
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Biotin and the biosynthesis of anthraquinoid pigments in Penicillium islandicum Sopp. by Ueno Y.; 1967 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251954
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Biotin Deficiency in Arthrobacter globiformis: Comparative Cell Ultrastructure and Nonreplacement of the Vitamin by Structurally Unrelated Compounds. by Chan EC, Zyk B, Gomersall M.; 1973 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251642
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Biotin dependency due to a defect in biotin transport. by Mardach R, Zempleni J, Wolf B, Cannon MJ, Jennings ML, Cress S, Boylan J, Roth S, Cederbaum S, Mock DM.; 2002 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151007
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Biotin Limitation in Sinorhizobium meliloti Strain 1021 Alters Transcription and Translation. by Heinz EB, Streit WR.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143622
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Biotin regulatory (bir) mutations of Escherichia coli. by Campbell A, Chang R, Barker D, Ketner G.; 1980 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=294133
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Biotin Transport and Accumulation by Cells of Lactobacillus plantarum I. General Properties of the System. by Waller JR, Lichstein HC.; 1965 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=315747
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Biotin Transport and Accumulation by Cells of Lactobacillus plantarum II. Kinetics of the System. by Waller JR, Lichstein HC.; 1965 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=315748
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Biotin Uptake by Cold-Shocked Cells, Spheroplasts, and Repressed Cells of Saccharomyces cerevisiae: Lack of Feedback Control. by Cicmanec JF, Lichstein HC.; 1974 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245673
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Biotin Uptake in Biotin Regulatory Mutant of Escherichia coli. by Pai CH.; 1973 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246449
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Biotin-avidin-amplified enzyme immunoassay for detection of herpes simplex virus antigen in clinical specimens. by Adler-Storthz K, Kendall C, Kennedy RC, Henkel RD, Dreesman GR.; 1983 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=272902
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Biotin-deficient Growth of Bacillus polymyxa. by Summers JW, Wyss O.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276920
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Biotin-labeled plasmid DNA probes for detection of epithelium-associated strains of lactobacilli. by Tannock GW.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184131
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Biotin-labeled synthetic oligodeoxyribonucleotides: chemical synthesis and uses as hybridization probes. by Chollet A, Kawashima EH.; 1985 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341094
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Biotin-requiring mutants of Escherichia coli K-12. by Del Campillo-Campbell A, Kayajanian G, Campbell A, Adhya S.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276941
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Biotin-tagged cDNA expression libraries displayed on lambda phage: a new tool for the selection of natural protein ligands. by Ansuini H, Cicchini C, Nicosia A, Tripodi M, Cortese R, Luzzago A.; 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137096
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Biotinyl and phosphotyrosinyl phosphoramidite derivatives useful in the incorporation of multiple reporter groups on synthetic oligonucleotides. by Misiura K, Durrant I, Evans MR, Gait MJ.; 1990 Aug 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331250
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Biotinylated Diaminopyridine: An Approach to Tagging Oligosaccharides and Exploring their Biology. by Rothenberg BE, Hayes BK, Toomre D, Manzi AE, Varki A.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48100
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Biotinylated DNA probes for exotoxin A and pilin genes in the differentiation of Pseudomonas aeruginosa strains. by Samadpour M, Moseley SL, Lory S.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266884
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Biotinylated probes in the electrophoretic mobility shift assay to examine specific dsDNA, ssDNA or RNA-protein interactions. by Ludwig LB, Hughes BJ, Schwartz SA.; 1995 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307283
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Biotinylation in vivo as a sensitive indicator of protein secretion and membrane protein insertion. by Jander G, Cronan JE Jr, Beckwith J.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178051
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Branched poly-labelled oligonucleotides: enhanced specificity of fork-shaped biotinylated oligoribonucleotides for antisense affinity selection. by Teigelkamp S, Ebel S, Will DW, Brown T, Beggs JD.; 1993 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311210
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Brassicaceae Express Multiple Isoforms of Biotin Carboxyl Carrier Protein in a Tissue-Specific Manner. by Thelen JJ, Mekhedov S, Ohlrogge JB.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88857
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Cell Permeability: a Factor in the Biotin-Oleate Relationship in Lactobacillus arabinosus II. Effect of Oleic Acid and Other Surfactants on Free Biotin Uptake. by Waller JR, Lichstein HC.; 1967 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=314982
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Characterization of cell wall proteins from yeast and mycelial cells of Candida albicans by labelling with biotin: comparison with other techniques. by Casanova M, Lopez-Ribot JL, Martinez JP, Sentandreu R.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258246
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Characterization of the Biotin Transport System in Saccharomyces cerevisiae. by Rogers TO, Lichstein HC.; 1969 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250127
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Characterization of the cDNA and gene coding for the biotin synthase of Arabidopsis thaliana. by Weaver LM, Yu F, Wurtele ES, Nikolau BJ.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157803
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Chemical and enzymatic biotin-labeling of oligodeoxyribonucleotides. by Kempe T, Sundquist WI, Chow F, Hu SL.; 1985 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340973
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Cloning and characterization of the Bacillus subtilis birA gene encoding a repressor of the biotin operon. by Bower S, Perkins J, Yocum RR, Serror P, Sorokin A, Rahaim P, Howitt CL, Prasad N, Ehrlich SD, Pero J.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176921
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Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon. by Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178169
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Comparison of biotinylated DNA and RNA probes for rapid detection of varicellazoster virus genome by in situ hybridization. by Forghani B, Yu GJ, Hurst JW.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269823
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Comparison of monoclonal antibody time-resolved fluoroimmunoassay with monoclonal antibody capture-biotinylated detector enzyme immunoassay for respiratory syncytial virus and parainfluenza virus antigen detection. by Hierholzer JC, Bingham PG, Coombs RA, Johansson KH, Anderson LJ, Halonen PE.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267535
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Conservation of the Biotin Regulon and the BirA Regulatory Signal in Eubacteria and Archaea. by Rodionov DA, Mironov AA, Gelfand MS.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187538
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Construction of a Biotin-Overproducing Strain of Serratia marcescens. by Sakurai N, Imai Y, Masuda M, Komatsubara S, Tosa T.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182377
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Contribution of Cysteine Desulfurase (NifS Protein) to the Biotin Synthase Reaction of Escherichia coli. by Kiyasu T, Asakura A, Nagahashi Y, Hoshino T.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101998
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Corepressor-induced organization and assembly of the biotin repressor: A model for allosteric activation of a transcriptional regulator. by Weaver LH, Kwon K, Beckett D, Matthews BW.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33419
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Deletion and Complementation Analysis of the Biotin Gene Cluster of Escherichia coli. by Cleary PP, Campbell A.; 1972 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251493
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Detection of bovine herpesvirus 1 DNA immobilized on nitrocellulose by hybridization with biotinylated DNA probes. by Dorman MA, Blair CD, Collins JK, Beaty BJ.; 1985 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271865
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Detection of enterotoxigenic Escherichia coli by colony hybridization with biotinylated enterotoxin probes. by Kirii Y, Danbara H, Komase K, Arita H, Yoshikawa M.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269376
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Detection of enterotoxigenic Escherichia coli by dot blot hybridization with biotinylated DNA probes. by Bialkowska-Hobrzanska H.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265896
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Detection of genital herpes simplex infections by a tissue culture-fluorescentantibody technique with biotin-avidin. by Nerurkar LS, Jacob AJ, Madden DL, Sever JL.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=272591
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Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes. by Brandt CD, Rakusan TA, Sison AV, Josephs SH, Saxena ES, Herzog KD, Parrott RH, Sever JL.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264992
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Detection of Norwalk virus antibodies and antigen with a biotin-avidin immunoassay. by Gary GW Jr, Kaplan JE, Stine SE, Anderson LJ.; 1985 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268374
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Detection of single base differences using biotinylated nucleotides with very long linker arms. by Livak KJ, Hobbs FW, Zagursky RJ.; 1992 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334239
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Detection of specific serum immunoglobulin M in nephropathia epidemica (Scandinavian epidemic nephropathy) by a biotin-avidin-amplified immunofluorescence method. by Settergren B, Juto P, Wadell G.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269156
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Detection of sub-picogram quantities of specific DNA sequences on blot hybridization with biotinylated probes. by Chan VT, Fleming KA, McGee JO.; 1985 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322111
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Determination of immunoglobulin M antibodies for hepatitis B core antigen with a capture enzyme immunoassay and biotin-labeled core antigen produced in Escherichia coli. by Vilja P, Turunen HJ, Leinikki PO.; 1985 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268482
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Development of a biotin-streptavidin-enhanced enzyme-linked immunosorbent assay which uses monoclonal antibodies for detection of group C rotaviruses. by Ojeh CK, Tsunemitsu H, Simkins RA, Saif LJ.; 1992 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265361
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Diagnosis of invasive candidiasis by detection of mannan antigen by using the avidin-biotin enzyme immunoassay. by Nakamura A, Ishikawa N, Suzuki H.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270339
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Differential incorporation of biotinylated nucleotides by terminal deoxynucleotidyl transferase. by Flickinger JL, Gebeyehu G, Buchman G, Haces A, Rashtchian A.; 1992 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=312365
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Direct quantification of specific mRNA using a selected biotinylated oligonucleotide by free solution capillary electrophoresis. by Reyes-Engel A, Dieguez-Lucena JL.; 1993 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=309190
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DNA orientation using specific avidin-ferritin biotin end labelling. by Theveny B, Revet B.; 1987 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340500
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DNA sequencing using biotinylated dideoxynucleotides and mass spectrometry. by Edwards JR, Itagaki Y, Ju J.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60203
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Effect of biotin on alkaloid production during submerged cultivation of Claviceps sp. strain SD-58. by Desai JD, Desai AJ, Patel HC.; 1983 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=242518
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Effect of Biotin on Fatty Acids and Phospholipids of Biotin-Sensitive Strains of Rhizobium japonicum. by Bunn CR, McNeill JJ, Elkan GH.; 1970 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284965
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Effect of pH and biotin on a circadian rhyythm of conidiation in Neurospora crassa. by West DJ.; 1975 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235734
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Efficient biotinylation and single-step purification of tagged transcription factors in mammalian cells and transgenic mice. by de Boer E, Rodriguez P, Bonte E, Krijgsveld J, Katsantoni E, Heck A, Grosveld F, Strouboulis J.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164612
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Electron microscopic visualization of tRNA genes with ferritin-avidin: biotin labels. by Broker TR, Angerer LM, Yen PH, Hershey ND, Davidson N.; 1978 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341989
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Engineering of a Bacillus subtilis Strain with Adjustable Levels of Intracellular Biotin for Secretory Production of Functional Streptavidin. by Wu SC, Wong SL.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123784
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Enhanced RACE method using specific enrichment by biotinylated oligonucleotides bound to streptavidin coated magnetic particles. by Lankiewicz S, Gisselmann G, Hatt H.; 1997 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146681
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Enzyme immunoassays in which biotinillated beta-lactamase is used for the detection of microbial antigens. by Yolken RH, Wee SB.; 1984 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271064
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Escherichia coli Biotin Holoenzyme Synthetase/bio Repressor Crystal Structure Delineates the Biotin- and DNA-Binding Domains. by Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50105
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Fluorescence-, isotope- or biotin-labeling of the 5 '-end of single-stranded DNA/RNA using T4 RNA ligase. by Kinoshita Y, Nishigaki K, Husimi Y.; 1997 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146945
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Fluoride-cleavable biotinylation phosphoramidite for 5[prime prime or minute]-endlabeling and affinity purification of synthetic oligonucleotides. by Fang S, Bergstrom DE.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140496
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Functional Analysis of Sinorhizobium meliloti Genes Involved in Biotin Synthesis and Transport. by Entcheva P, Phillips DA, Streit WR.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123963
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Gene mapping and gene enrichment by the avidin-biotin interaction: use of cytochrome-c as a polyamine bridge. by Sodja A, Davidson N.; 1978 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341990
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Genes for two subunits of acetyl coenzyme A carboxylase of Anabaena sp. strain PCC 7120: biotin carboxylase and biotin carboxyl carrier protein. by Gornicki P, Scappino LA, Haselkorn R.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204996
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Genetic Analysis of the System that Reduces Biotin-d-Sulfoxide in Escherichia coli. by Dykhuizen D.; 1973 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246297
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Genetic and Biochemical Analysis of the Biotin Loci of Escherichia coli K-12. by Rolfe B, Eisenberg MA.; 1968 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252325
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Genetics of biotin biosynthesis in Bacillus subtilis. by Pai CH.; 1975 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285605
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Highly efficient chemical synthesis of 2'-O-methyloligoribonucleotides and tetrabiotinylated derivatives; novel probes that are resistant to degradation by RNA or DNA specific nucleases. by Sproat BS, Lamond AI, Beijer B, Neuner P, Ryder U.; 1989 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317781
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Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. by Solorzano-Vargas RS, Pacheco-Alvarez D, Leon-Del-Rio A.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122768
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Identification and characterization of transcripts from the biotin biosynthetic operon of Bacillus subtilis. by Perkins JB, Bower S, Howitt CL, Yocum RR, Pero J.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178513
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Immunocytochemical detection of antibodies to Epstein-Barr virus nuclear antigen by a streptavidin-biotin-complex assay. by Musiani M, Zerbini M, Plazzi M, Gentilomi G, La Placa M.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266505
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Immunoglobulin M Capture Assay for Serologic Confirmation of Early Lyme Disease: Analysis of Immune Complexes with Biotinylated Borrelia burgdorferi Sonicate Enhanced with Flagellin Peptide Epitope. by Brunner M, Stein S, Mitchell PD, Sigal LH.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104692
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Improved immunoglobulin M serodiagnosis in Lyme borreliosis by using a mucapture enzyme-linked immunosorbent assay with biotinylated Borrelia burgdorferi flagella. by Hansen K, Pii K, Lebech AM.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269723
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In vitro synthesis and and regulation of the biotin enzymes of Escherichia coli K-12. by Prakash O, Eisenberg MA.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222349
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In vivo labeling of Escherichia coli cell envelope proteins with Nhydroxysuccinimide esters of biotin. by Bradburne JA, Godfrey P, Choi JH, Mathis JN.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202171
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Intersubunit Contacts Made by Tryptophan 120 with Biotin are Essential for Both Strong Biotin Binding and Biotin-Induced Tighter Subunit Association of Streptavidin. by Sano T, Cantor CR.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42129
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Isolation of a cDNA Encoding Human Holocarboxylase Synthetase by Functional Complementation of a Biotin Auxotroph of Escherichia coli. by Leon-Del-Rio A, Leclerc D, Akerman B, Wakamatsu N, Gravel RA.; 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41997
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Leishmania Antigen Nonspecific Binding to Avidin in Biotin-Avidin Immunoassays. by Agudelo S.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95943
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Lipid synthesis in mycobacteria: characterization of the biotin carboxyl carrier protein genes from Mycobacterium leprae and M. tuberculosis. by Norman E, De Smet KA, Stoker NG, Ratledge C, Wheeler PR, Dale JW.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205389
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Mapping Chromosome Band 11q23 in Human Acute Leukemia with Biotinylated Probes: Identification of 11q23 Translocation Breakpoints with a Yeast Artificial Chromosome. by Rowley JD, Diaz MO, Espinosa R III, Patel YD, van Melle E, Ziemin S, Taillon-Miller P, Lichter P, Evans GA, Kersey JH, Ward DC, Domer PH, Beau MM.; 1990 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55164
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Mapping of single-copy DNA sequences on human chromosomes by in situ hybridization with biotinylated probes: enhancement of detection sensitivity by intensified-fluorescence digital-imaging microscopy. by Viegas-Pequignot E, Dutrillaux B, Magdelenat H, Coppey-Moisan M.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286516
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Mechanism of Folate Transport in Lactobacillus casei: Evidence for a Component Shared with the Thiamine and Biotin Transport Systems. by Henderson GB, Zevely EM, Huennekens FM.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218314
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Metabolism of Biotin and Analogues of Biotin by Microorganisms II. Further Studies on the Conversion of d-Biotin to Biotin Vitamers by Lactobacillus plantarum. by Birnbaum J, Lichstein HC.; 1966 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276353
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Metabolism of Biotin and Analogues of Biotin by Microorganisms III. Degradation of Oxybiotin and Desthiobiotin by Lactobacillus plantarum. by Birnbaum J, Lichstein HC.; 1966 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276354
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Metabolism of Biotin and Analogues of Biotin by Microorganisms IV. Degradation of Biotin, Oxybiotin, and Desthiobiotin by Lactobacillus casei. by Birnbaum J, Lichstein HC.; 1966 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276355
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Mode of action of alpha-dehydrobiotin, a biotin analogue. by Eisenberg MA.; 1975 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235713
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Mode of action of the biotin antimetabolites actithiazic acid and alphamethyldethiobiotin. by Eisenberg MA, Hsiung SC.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181820
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Model for studying virus attachment: identification and quantitation of Epstein-Barr virus-binding cells by using biotinylated virus in flow cytometry. by Inghirami G, Nakamura M, Balow JE, Notkins AL, Casali P.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253404
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Molecular breeding of a biotin-hyperproducing Serratia marcescens strain. by Sakurai N, Imai Y, Masuda M, Komatsubara S, Tosa T.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182441
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Molecular Cloning and Characterization of the cDNA Coding for the BiotinContaining Subunit of 3-Methylcrotonoyl-CoA Carboxylase: Identification of the Biotin Carboxylase and Biotin-Carrier Domains. by Song J, Wurtele ES, Nikolau BJ.; 1994 Jun 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44080
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Molecular cloning and characterization of the cDNA coding for the biotin-containing subunit of the chloroplastic acetyl-coenzyme A carboxylase. by Choi JK, Yu F, Wurtele ES, Nikolau BJ.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157628
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Molecular Cloning and Characterization of Two Genes for the Biotin Carboxylase and Carboxyltransferase Subunits of Acetyl Coenzyme A Carboxylase in Myxococcus xanthus. by Kimura Y, Miyake R, Tokumasu Y, Sato M.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110990
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Molecular cloning of the biotinylated subunit of 3-methylcrotonyl-coenzyme A carboxylase of Arabidopsis thaliana. by Weaver LM, Lebrun L, Franklin A, Huang L, Hoffman N, Wurtele ES, Nikolau BJ.; 1995 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=157220
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Molybdenum cofactor requirement for biotin sulfoxide reduction in Escherichia coli. by del Campillo-Campbell A, Campbell A.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216530
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Mutant of Escherichia coli with Derepressed Levels of the Biotin Biosynthetic Enzymes. by Pai CH.; 1972 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251560
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Non-radioactive chemical sequencing of biotin labelled DNA. by Richterich P.; 1989 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317587
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Non-radioactive hybridization probes prepared by the chemical labelling of DNA and RNA with a novel reagent, photobiotin. by Forster AC, McInnes JL, Skingle DC, Symons RH.; 1985 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341032
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Novel biotinylated nucleotide--analogs for labeling and colorimetric detection of DNA. by Gebeyehu G, Rao PY, SooChan P, Simms DA, Klevan L.; 1987 Jun 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340877
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Organization and nucleotide sequences of the genes encoding the biotin carboxyl carrier protein and biotin carboxylase protein of Pseudomonas aeruginosa acetyl coenzyme A carboxylase. by Best EA, Knauf VC.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206813
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Oxaloacetate Synthesis in the Methanarchaeon Methanosarcina barkeri: Pyruvate Carboxylase Genes and a Putative Escherichia coli-Type Bifunctional Biotin Protein Ligase Gene (bpl/birA) Exhibit a Unique Organization. by Mukhopadhyay B, Purwantini E, Kreder CL, Wolfe RS.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95260
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Partial Purification and Properties of d-Desthiobiotin Synthetase from Escherichia coli. by Cheeseman P, Pai CH.; 1970 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285051
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p-Diazobenzoyl-biocytin: a new biotinylating reagent for DNA. by Rothenberg JM, Wilchek M.; 1988 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338378
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Photocleavable Biotin Derivatives: A Versatile Approach for the Isolation of Biomolecules. by Olejnik J, Sonar S, Krzymanska-Olejnik E, Rothschild KJ.; 1995 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41385
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Photocleavable biotin phosphoramidite for 5'-end-labeling, affinity purification and phosphorylation of synthetic oligonucleotides. by Olejnik J, Krzymanska-Olejnik E, Rothschild KJ.; 1996 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145639
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Practical and economical method for using biotinylated DNA probes with bacterial colony blots to identify diarrhea-causing Escherichia coli. by Gicquelais KG, Baldini MM, Martinez J, Maggi L, Martin WC, Prado V, Kaper JB, Levine MM.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268211
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Preparation and characterization of biotinylated psoralen. by Saffran WA, Welsh JT, Knobler RM, Gasparro FP, Cantor CR, Edelson RL.; 1988 Aug 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338404
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Production of L-alanine by biotin-deficient Micrococcus sodonensis. by Perry JJ.; 1967 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276801
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Properties and Purification of an Active Biotinylated Lactose Permease from Escherichia coli. by Consler TG, Persson BL, Jung H, Zen KH, Jung K, Prive GG, Verner GE, Kaback HR.; 1993 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47049
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Properties of alpha-dehydrobiotin-resistant mutants of Escherichia coli K-12. by Eisenburg MA, Mee B, Prakash O, Eisenburg MR.; 1975 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235640
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Quantitative determination of staphylococcal enterotoxin A by an enzyme-linked immunosorbent assay using a combination of polyclonal and monoclonal antibodies and biotin-streptavidin interaction. by Edwin C.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267602
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Rapid detection of herpes simplex virus in clinical specimens by use of a capture biotin-streptavidin enzyme-linked immunosorbent assay. by Nerurkar LS, Namba M, Brashears G, Jacob AJ, Lee YJ, Sever JL.; 1984 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271257
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Rapid production of vector-free biotinylated probes using the polymerase chain reaction. by Lo YM, Mehal WZ, Fleming KA.; 1988 Sep 12; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338597
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Rapid selection of aminoacyl-tRNAs based on biotinylation of alpha-NH2 group of charged amino acids. by Putz J, Wientges J, Sissler M, Giege R, Florentz C, Schwienhorst A.; 1997 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146665
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Rapid turnover of microtubule-associated protein MAP2 in the axon revealed by microinjection of biotinylated MAP2 into cultured neurons. by Okabe S, Hirokawa N.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287402
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Recombinant antigen-based avidin-biotin microtiter enzyme-linked immunosorbent assay for serodiagnosis of invasive amebiasis. by Shenai BR, Komalam BL, Arvind AS, Krishnaswamy PR, Rao PV.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228901
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Recombinant Rhizobium meliloti strains with extra biotin synthesis capability. by Streit WR, Phillips DA.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168129
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Regulation of Biotin Transport in Saccharomyces cerevisiae. by Rogers TO, Lichstein HC.; 1969 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250128
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Repression of Biotin Biosynthesis in Escherichia coli During Growth on Biotin Vitamers. by Campbell A, Campillo-Campbell AD, Barker D.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=224777
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Selective amplification via biotin- and restriction-mediated enrichment (SABRE), a novel selective amplification procedure for detection of differentially expressed mRNAs. by Lavery DJ, Lopez-Molina L, Fleury-Olela F, Schibler U.; 1997 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21244
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Selective enrichment of specific DNA, cDNA and RNA sequences using biotinylated probes, avidin and copper-chelate agarose. by Welcher AA, Torres AR, Ward DC.; 1986 Dec 22; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341353
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Separation of complementary strands of plasmid DNA using the biotin-avidin system and its application to heteroduplex formation and RNA/DNA hybridizations in electron microscopy. by Delius H, van Heerikhuizen H, Clarke J, Koller B.; 1985 Aug 12; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=321883
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Serologic Detection of Actinobacillus pleuropneumoniae in Swine by Capsular Polysaccharide-Biotin-Streptavidin Enzyme-Linked Immunosorbent Assay. by Inzana TJ, Fenwick B.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87924
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Sinorhizobium meliloti Cells Require Biotin and either Cobalt or Methionine for Growth. by Watson RJ, Heys R, Martin T, Savard M.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93089
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Site-Directed Mutagenesis Studies of the High-Affinity Streptavidin-Biotin Complex: Contributions of Tryptophan Residues 79, 108, and 120. by Chilkoti A, Tan PH, Stayton PS.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42598
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Solid phase DNA sequencing using the biotin-avidin system. by Stahl S, Hultman T, Olsson A, Moks T, Uhlen M.; 1988 Apr 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336449
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Structural analysis, plastid localization, and expression of the biotin carboxylase subunit of acetyl-coenzyme A carboxylase from tobacco. by Shorrosh BS, Roesler KR, Shintani D, van de Loo FJ, Ohlrogge JB.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157403
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Studies towards the development of chemically synthesized non-radioactive biotinylated nucleic acid hybridization probes. by Al-Hakim AH, Hull R.; 1986 Dec 22; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341348
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Synthesis and cytotoxicity of a biotinylated CC-1065 analogue. by Wang Y, Yuan H, Wright SC, Wang H, Larrick JW.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65513
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Synthesis and hybridization of a series of biotinylated oligonucleotides. by Cook AF, Vuocolo E, Brakel CL.; 1988 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336576
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Synthesis and use of labelled nucleoside phosphoramidite building blocks bearing a reporter group: biotinyl, dinitrophenyl, pyrenyl and dansyl. by Roget A, Bazin H, Teoule R.; 1989 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334873
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Synthesis of 7-Oxo-8-Aminopelargonic Acid, a Biotin Vitamer, in Cell-free Extracts of Escherichia coli Biotin Auxotrophs. by Eisenberg MA, Star C.; 1968 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252447
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Synthesis of Desthiobiotin from 7,8-Diaminopel-argonic Acid in Biotin Auxotrophs of Escherichia coli K-12. by Eisenberg MA, Krell K.; 1969 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=315317
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The Bacillus thuringiensis insecticidal toxin binds biotin-containing proteins. by Du C, Nickerson KW.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168080
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The genes encoding the biotin carboxyl carrier protein and biotin carboxylase subunits of Bacillus subtilis acetyl coenzyme A carboxylase, the first enzyme of fatty acid synthesis. by Marini P, Li SJ, Gardiol D, Cronan JE Jr, de Mendoza D.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177574
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The Role of Biotin in Regulating 3-Methylcrotonyl-Coenzyme A Carboxylase Expression in Arabidopsis. by Che P, Weaver LM, Wurtele ES, Nikolau BJ.; 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166907
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The use of biotinylated hybridization probes for routine analysis of unique sequences in human DNA. by Koch J, Gregersen N, Kolvraa S, Bolund L.; 1986 Sep 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311729
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Three-Dimensional Structures of Avidin and the Avidinbiotin Complex. by Livnah O, Bayer EA, Wilchek M, Sussman JL.; 1993 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46657
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Two-Step Affinity Purification of U7 Small Nuclear Ribonucleoprotein Particles Using Complementary Biotinylated 2'-O-Methyl Oligoribonucleotides. by Smith HO, Tabiti K, Schaffner G, Soldati D, Albrecht U.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52805
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Typing of herpes simplex virus by capture biotin-streptavidin enzyme-linked immunosorbent assay and comparison with restriction endonuclease analysis and immunofluorescence method using monoclonal antibodies. by Nerurkar LS, Miller NR, Namba M, Monzon M, Brashears G, Scherba G, Sever JL.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265839
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Uptake of extracellular biotin by Escherichia coli biotin prototrophs. by Cicmanec JF, Lichstein HC.; 1978 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222004
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Use of a biotinylated DNA probe to detect bacteria transduced by bacteriophage P1 in soil. by Zeph LR, Stotzky G.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184176
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Use of bio-lac fusion strains to study regulation of biotin biosynthesis in Escherichia coli. by Barker DF, Campbell AM.; 1980 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=294364
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Use of biotinylated beta-lactams and chemiluminescence for study and purification of penicillin-binding proteins in bacteria. by Dargis M, Malouin F.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188136
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Use of biotinylated DNA probes in colony hybridization. by Haas MJ, Fleming DJ.; 1986 May 12; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339833
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Use of the biotin-avidin system to study the specificity of antibodies against respiratory syncytial virus. by Anderson LJ, Coombs RA, Tsou C, Hierholzer JC.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271219
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 biotin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “biotin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for biotin (hyperlinks lead to article summaries): •
3-Hydroxypropionic acid and methylcitric acid are not reliable indicators of marginal biotin deficiency in humans. Author(s): Mock DM, Henrich-Shell CL, Carnell N, Stumbo P, Mock NI. Source: The Journal of Nutrition. 2004 February; 134(2): 317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14747666&dopt=Abstract
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A biotin derivative blocks parasite induced novel permeation pathways in Plasmodium falciparum-infected erythrocytes. Author(s): Baumeister S, Endermann T, Charpian S, Nyalwidhe J, Duranton C, Huber S, Kirk K, Lang F, Lingelbach K. Source: Molecular and Biochemical Parasitology. 2003 November; 132(1): 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563535&dopt=Abstract
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A case of partial biotinidase deficiency associated with autism. Author(s): Zaffanello M, Zamboni G, Fontana E, Zoccante L, Tato L. Source: Neuropsychology, Development, and Cognition. Section C, Child Neuropsychology : a Journal on Normal and Abnormal Development in Childhood and Adolescence. 2003 September; 9(3): 184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13680408&dopt=Abstract
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A direct streptavidin-binding assay does not accurately quantitate biotin in human urine. Author(s): Mock DM, Nyalala JO, Raguseo RM. Source: The Journal of Nutrition. 2001 August; 131(8): 2208-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481419&dopt=Abstract
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A new biotin derivative-DOTA conjugate as a candidate for pretargeted diagnosis and therapy of tumors. Author(s): Sabatino G, Chinol M, Paganelli G, Papi S, Chelli M, Leone G, Papini AM, De Luca A, Ginanneschi M. Source: Journal of Medicinal Chemistry. 2003 July 3; 46(14): 3170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825956&dopt=Abstract
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A new quantitative analytical method of serum biotinidase activity using biocytin as a substrate and its clinical significance in Japan. Author(s): Kumasaka K, Muratsugu M, Fukui T, Kimura M, Takagi Y, Hashizume N. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 April; 306(1-2): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282096&dopt=Abstract
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A nonpermeant biotin derivative gains access to the parasitophorous vacuole in Plasmodium falciparum-infected erythrocytes permeabilized with streptolysin O. Author(s): Nyalwidhe J, Baumeister S, Hibbs AR, Tawill S, Papakrivos J, Volker U, Lingelbach K. Source: The Journal of Biological Chemistry. 2002 October 18; 277(42): 40005-11. Epub 2002 August 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186876&dopt=Abstract
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A receptor-mediated gene delivery system using streptavidin and biotin-derivatized, pegylated epidermal growth factor. Author(s): Lee H, Kim TH, Park TG. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2002 September 18; 83(1): 109-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220843&dopt=Abstract
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A streptavidin-biotin binding system that minimizes blocking by endogenous biotin. Author(s): Hamblett KJ, Kegley BB, Hamlin DK, Chyan MK, Hyre DE, Press OW, Wilbur DS, Stayton PS. Source: Bioconjugate Chemistry. 2002 May-June; 13(3): 588-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009950&dopt=Abstract
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A two-component modular approach for enhancing T-cell activation utilizing a unique anti-FcgammaRI-streptavidin construct and microspheres coated with biotinylated-antigen. Author(s): Walsh MC, Banas JA, Mudzinski SP, Preissler MT, Graziano RF, Gosselin EJ. Source: Biomolecular Engineering. 2003 January; 20(1): 21-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485681&dopt=Abstract
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A typing system for neisseria gonorrhoeae based on biotinylated oligonucleotide probes to PIB gene variable regions. Author(s): Thompson DK, Deal CD, Ison CA, Zenilman JM, Bash MC. Source: The Journal of Infectious Diseases. 2000 May; 181(5): 1652-60. Epub 2000 May 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10823765&dopt=Abstract
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Abeta(1-40) peptide radiopharmaceuticals for brain amyloid imaging: (111)In chelation, conjugation to poly(ethylene glycol)-biotin linkers, and autoradiography with Alzheimer's disease brain sections. Author(s): Kurihara A, Pardridge WM. Source: Bioconjugate Chemistry. 2000 May-June; 11(3): 380-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821654&dopt=Abstract
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Amplification of antigen-antibody interactions based on biotin labeled proteinstreptavidin network complex using impedance spectroscopy. Author(s): Pei R, Cheng Z, Wang E, Yang X. Source: Biosensors & Bioelectronics. 2001 August; 16(6): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11672649&dopt=Abstract
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An FKBP12 binding assay based upon biotinylated FKBP12. Author(s): Carreras CW, Fu H, Santi DV. Source: Analytical Biochemistry. 2001 November 1; 298(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673895&dopt=Abstract
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An improved protocol of biotinylated tyramine-based immunohistochemistry minimizing nonspecific background staining. Author(s): Kim SH, Shin YK, Lee KM, Lee JS, Yun JH, Lee SM. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 January; 51(1): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502763&dopt=Abstract
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Analysis of the envelope proteins of heat-shocked Vibrio parahaemolyticus cells by immunoblotting and biotin-labeling methods. Author(s): Wong HC, Chen YC. Source: Microbiology and Immunology. 2003; 47(5): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825892&dopt=Abstract
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Analytical techniques for determining biotin. Author(s): Livaniou E, Costopoulou D, Vassiliadou I, Leondiadis L, Nyalala JO, Ithakissios DS, Evangelatos GP. Source: J Chromatogr A. 2000 June 9; 881(1-2): 331-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905717&dopt=Abstract
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Avidin-biotin ELISA for measurement of prothrombin in human plasma. Author(s): Koldas M, Uras F. Source: Thrombosis Research. 2001 May 1; 102(3): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369415&dopt=Abstract
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Biotin and biocytin uptake into cultured primary calf brain microvessel endothelial cells of the blood-brain barrier. Author(s): Baur B, Baumgartner ER. Source: Brain Research. 2000 March 10; 858(2): 348-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10708686&dopt=Abstract
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Biotin dependency due to a defect in biotin transport. Author(s): Mardach R, Zempleni J, Wolf B, Cannon MJ, Jennings ML, Cress S, Boylan J, Roth S, Cederbaum S, Mock DM. Source: The Journal of Clinical Investigation. 2002 June; 109(12): 1617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070309&dopt=Abstract
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Biotin in metabolism and its relationship to human disease. Author(s): Pacheco-Alvarez D, Solorzano-Vargas RS, Del Rio AL. Source: Archives of Medical Research. 2002 September-October; 33(5): 439-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459313&dopt=Abstract
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Biotin in metabolism and molecular biology. Author(s): McMahon RJ. Source: Annual Review of Nutrition. 2002; 22: 221-39. Epub 2002 January 04. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055344&dopt=Abstract
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Biotin reagents for antibody pretargeting. 5. Additional studies of biotin conjugate design to provide biotinidase stability. Author(s): Wilbur DS, Hamlin DK, Chyan MK, Kegley BB, Pathare PM. Source: Bioconjugate Chemistry. 2001 July-August; 12(4): 616-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459467&dopt=Abstract
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Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase, and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells. Author(s): Wiedmann S, Eudy JD, Zempleni J. Source: The Journal of Nutrition. 2003 March; 133(3): 716-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612142&dopt=Abstract
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Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells. Author(s): Manthey KC, Griffin JB, Zempleni J. Source: The Journal of Nutrition. 2002 May; 132(5): 887-92. Erratum In: J Nutr 2002 August; 132(8): 2326. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983808&dopt=Abstract
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Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system. Author(s): Balamurugan K, Ortiz A, Said HM. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2003 July; 285(1): G73-7. Epub 2003 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646417&dopt=Abstract
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Biotin uptake into human peripheral blood mononuclear cells increases early in the cell cycle, increasing carboxylase activities. Author(s): Stanley JS, Mock DM, Griffin JB, Zempleni J. Source: The Journal of Nutrition. 2002 July; 132(7): 1854-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097659&dopt=Abstract
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Biotin: the forgotten vitamin. Author(s): Said HM. Source: The American Journal of Clinical Nutrition. 2002 February; 75(2): 179-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815306&dopt=Abstract
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Biotin-dependent carboxylase activities in different CNS and skin-derived cells, and their sensitivity to biotin-depletion. Author(s): Suormala T, Wiesmann UN, Cruz F, Wolf A, Daschner M, Limat A, Fowler B, Baumgartner ER. Source: Int J Vitam Nutr Res. 2002 July; 72(4): 278-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214565&dopt=Abstract
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Biotinidase catalyzes debiotinylation of histones. Author(s): Ballard TD, Wolff J, Griffin JB, Stanley JS, van Calcar S, Zempleni J. Source: European Journal of Nutrition. 2002 April; 41(2): 78-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083317&dopt=Abstract
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Biotinidase deficiency: a treatable genetic disorder in the Saudi population. Author(s): Joshi S, al-Essa MA, Archibald A, Ozand PT. Source: East Mediterr Health J. 1999 November; 5(6): 1213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924114&dopt=Abstract
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Biotinidase deficiency: clinical and MRI findings consistent with myelopathy. Author(s): Wiznitzer M, Bangert BA. Source: Pediatric Neurology. 2003 July; 29(1): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679123&dopt=Abstract
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Biotinidase deficiency: result of treatment with biotin from age 12 years. Author(s): Casado de Frias E, Campos-Castello J, Careaga Maldonado J, Perez Cerda C. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1997; 1(5-6): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728214&dopt=Abstract
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Biotinidase deficiency--a treatable entity. Author(s): Gulati S, Passi GR, Kumar A, Kabra M, Kalra V, Verma IC. Source: Indian J Pediatr. 2000 June; 67(6): 464-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10932969&dopt=Abstract
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Biotinidase determination in serum and dried blood spots--high sensitivity fluorimetric ultramicro-assay. Author(s): Broda E, Baumgartner ER, Scholl S, Stopsack M, Horn A, Rhode H. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 December; 314(1-2): 175-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718693&dopt=Abstract
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Biotin-tagged cDNA expression libraries displayed on lambda phage: a new tool for the selection of natural protein ligands. Author(s): Ansuini H, Cicchini C, Nicosia A, Tripodi M, Cortese R, Luzzago A. Source: Nucleic Acids Research. 2002 August 1; 30(15): E78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140340&dopt=Abstract
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Biotin-ubiquitin tagging of mammalian proteins in Escherichia coli. Author(s): Wang T, Evdokimov E, Yiadom K, Yan Z, Chock PB, Yang DC. Source: Protein Expression and Purification. 2003 July; 30(1): 140-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821332&dopt=Abstract
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Biotinylated indoles as probes for indole-binding proteins. Author(s): Dolusic E, Kowalczyk M, Magnus V, Sandberg G, Normanly J. Source: Bioconjugate Chemistry. 2001 March-April; 12(2): 152-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11312675&dopt=Abstract
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Biotinylated synthetic chemokines: their use for the development of nonradioactive whole-cell binding assays. Author(s): Thierry AC, Perrenoud G, Pinaud S, Bigler N, Denis B, Roggero M, Moulon C, Demotz S. Source: Journal of Biomolecular Screening : the Official Journal of the Society for Biomolecular Screening. 2003 June; 8(3): 316-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857385&dopt=Abstract
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Biotinylation of antisense oligonucleotides does not alter lipofectin enhanced cellular uptake in prostate cancer cell lines. Author(s): Rubenstein M, Mirochnik Y, Slobodskoy L, Guinan P. Source: Methods Find Exp Clin Pharmacol. 2001 November; 23(9): 487-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876021&dopt=Abstract
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Biotinylation of histones in human cells. Effects of cell proliferation. Author(s): Stanley JS, Griffin JB, Zempleni J. Source: European Journal of Biochemistry / Febs. 2001 October; 268(20): 5424-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606205&dopt=Abstract
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Biotinylation sites of tumor necrosis factor-alpha determined by liquid chromatography-mass spectrometry. Author(s): Magni F, Curnis F, Marazzini L, Colombo R, Sacchi A, Corti A, Kienle MG. Source: Analytical Biochemistry. 2001 November 15; 298(2): 181-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700972&dopt=Abstract
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Biotinyl-tyramide-based in situ hybridization signal patterns distinguish human papillomavirus type and grade of cervical intraepithelial neoplasia. Author(s): Evans MF, Mount SL, Beatty BG, Cooper K. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2002 December; 15(12): 1339-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481016&dopt=Abstract
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Cell biotinylation provides a sensitive and effective detection technique for cellular adhesion assays: comparison with existing methods. Author(s): Mendis D, Ginon I, Louis H, McGregor JL, Poston RN. Source: Journal of Immunological Methods. 2001 July 1; 253(1-2): 57-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384669&dopt=Abstract
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Cell-surface recognition of biotinylated membrane proteins requires very long spacer arms: an example from glucose-transporter probes. Author(s): Hashimoto M, Yang J, Holman GD. Source: Chembiochem : a European Journal of Chemical Biology. 2001 January 8; 2(1): 52-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828427&dopt=Abstract
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Cerebrospinal fluid levels of biotin in various neurological disorders. Author(s): Anagnostouli M, Livaniou E, Nyalala JO, Evangelatos G, Zournas C, Ithakissios DS, Papageorgiou C. Source: Acta Neurologica Scandinavica. 1999 June; 99(6): 387-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577274&dopt=Abstract
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Children with profound biotinidase deficiency should be treated with biotin regardless of their residual enzyme activity or genotype. Author(s): Wolf B. Source: European Journal of Pediatrics. 2002 March; 161(3): 167-8; Author Reply 169. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998918&dopt=Abstract
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Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects of delayed versus immediate umbilical cord clamping in preterm neonates. Author(s): Strauss RG, Mock DM, Johnson K, Mock NI, Cress G, Knosp L, Lobas L, Schmidt RL. Source: Transfusion. 2003 August; 43(8): 1168-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869126&dopt=Abstract
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Clinical and neuropsychological outcome in 33 patients with biotinidase deficiency ascertained by nationwide newborn screening and family studies in Austria. Author(s): Moslinger D, Stockler-Ipsiroglu S, Scheibenreiter S, Tiefenthaler M, Muhl A, Seidl R, Strobl W, Plecko B, Suormala T, Baumgartner ER. Source: European Journal of Pediatrics. 2001 May; 160(5): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388594&dopt=Abstract
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Clinical optimization of pretargeted radioimmunotherapy with antibody-streptavidin conjugate and 90Y-DOTA-biotin. Author(s): Breitz HB, Weiden PL, Beaumier PL, Axworthy DB, Seiler C, Su FM, Graves S, Bryan K, Reno JM. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 January; 41(1): 131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647616&dopt=Abstract
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Complete biotinidase deficiency presenting as reversible progressive ataxia and sensorineural deafness. Author(s): Tsao CY, Kien CL. Source: Journal of Child Neurology. 2002 February; 17(2): 146. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952077&dopt=Abstract
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Conservation of biotindase in mammals and identification of the putative biotinidase gene in Drosophila melanogaster. Author(s): Swango KL, Wolf B. Source: Molecular Genetics and Metabolism. 2001 December; 74(4): 492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11749055&dopt=Abstract
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Cutaneous and neurologic manifestations of biotinidase deficiency. Author(s): Navarro PC, Guerra A, Alvarez JG, Ortiz FJ. Source: International Journal of Dermatology. 2000 May; 39(5): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10849128&dopt=Abstract
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Detection of biotinylated proteins in polyacrylamide gels using an avidin-fluorescein conjugate. Author(s): Nakamura M, Tsumoto K, Ishimura K, Kumagai I. Source: Analytical Biochemistry. 2002 May 15; 304(2): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009700&dopt=Abstract
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Determination of biotin and folate in infant formula and milk by optical biosensorbased immunoassay. Author(s): Indyk HE, Evans EA, Bostrom Caselunghe MC, Persson BS, Finglas PM, Woollard DC, Filonzi EL. Source: J Aoac Int. 2000 September-October; 83(5): 1141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11048855&dopt=Abstract
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Determination of biotin levels in cerebrospinal fluid samples. Author(s): Livaniou E, Nyalala JO, Anagnostouli M, Papageorgiou C, Evangelatos GP, Ithakissios DS. Source: Journal of Pharmaceutical and Biomedical Analysis. 1999 December; 21(4): 875-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701954&dopt=Abstract
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Determination of matrix metalloproteinase activity using biotinylated gelatin. Author(s): Ratnikov B, Deryugina E, Leng J, Marchenko G, Dembrow D, Strongin A. Source: Analytical Biochemistry. 2000 November 1; 286(1): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038285&dopt=Abstract
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Determination of tumor necrosis factor-alpha levels in dengue virus infected patients by sensitive biotin-streptavidin enzyme-linked immunosorbent assay. Author(s): Kittigul L, Temprom W, Sujirarat D, Kittigul C. Source: Journal of Virological Methods. 2000 October; 90(1): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11011080&dopt=Abstract
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Development of new biotin/streptavidin reagents for pretargeting. Author(s): Wilbur DS, Pathare PM, Hamlin DK, Stayton PS, To R, Klumb LA, Buhler KR, Vessella RL. Source: Biomolecular Engineering. 1999 December 31; 16(1-4): 113-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796993&dopt=Abstract
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Diaminobiotin and desthiobiotin have biotin-like activities in Jurkat cells. Author(s): Rodriguez-Melendez R, Lewis B, McMahon RJ, Zempleni J. Source: The Journal of Nutrition. 2003 May; 133(5): 1259-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730407&dopt=Abstract
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Differential incorporation of biotinylated polyamines by transglutaminase 2. Author(s): Jeon JH, Kim CW, Shin DM, Kim K, Cho SY, Kwon JC, Choi KH, Kang HS, Kim IG. Source: Febs Letters. 2003 January 16; 534(1-3): 180-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527383&dopt=Abstract
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Easily reversible desthiobiotin binding to streptavidin, avidin, and other biotinbinding proteins: uses for protein labeling, detection, and isolation. Author(s): Hirsch JD, Eslamizar L, Filanoski BJ, Malekzadeh N, Haugland RP, Beechem JM, Haugland RP. Source: Analytical Biochemistry. 2002 September 15; 308(2): 343-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419349&dopt=Abstract
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Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects. Author(s): Baez-Saldana A, Zendejas-Ruiz I, Revilla-Monsalve C, Islas-Andrade S, Cardenas A, Rojas-Ochoa A, Vilches A, Fernandez-Mejia C. Source: The American Journal of Clinical Nutrition. 2004 February; 79(2): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14749229&dopt=Abstract
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End-labeling of long DNA fragments with biotin and detection of DNA immobilized on magnetic beads. Author(s): Xu H, Zhang S, Liu D, Liang CC. Source: Molecular Biotechnology. 2001 February; 17(2): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11395865&dopt=Abstract
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Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells. Author(s): Minko T, Paranjpe PV, Qiu B, Lalloo A, Won R, Stein S, Sinko PJ. Source: Cancer Chemotherapy and Pharmacology. 2002 August; 50(2): 143-50. Epub 2002 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172980&dopt=Abstract
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Ex vivo biocompatibility of avidin-agarose: a new device for direct adsorption of biotinylated antibodies from human whole blood. Author(s): Bosch T, Lennertz A, Duhr C, Fink E, Samtleben W. Source: Artificial Organs. 2000 September; 24(9): 696-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11012539&dopt=Abstract
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Examination of the signal peptide region of human biotinidase using a baculovirus expression system. Author(s): Norrgard KJ, Hymes J, Wolf B. Source: Molecular Genetics and Metabolism. 2000 January; 69(1): 56-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655158&dopt=Abstract
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Exposure to UV light causes increased biotinylation of histones in Jurkat cells. Author(s): Peters DM, Griffin JB, Stanley JS, Beck MM, Zempleni J. Source: American Journal of Physiology. Cell Physiology. 2002 September; 283(3): C87884. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176744&dopt=Abstract
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Expression in Escherichia coli of N- and C-terminally deleted human holocarboxylase synthetase. Influence of the N-terminus on biotinylation and identification of a minimum functional protein. Author(s): Campeau E, Gravel RA. Source: The Journal of Biological Chemistry. 2001 April 13; 276(15): 12310-6. Epub 2000 December 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11124959&dopt=Abstract
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Familial infantile bilateral striatal necrosis: clinical features and response to biotin treatment. Author(s): Straussberg R, Shorer Z, Weitz R, Basel L, Kornreich L, Corie CI, Harel L, Djaldetti R, Amir J. Source: Neurology. 2002 October 8; 59(7): 983-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374138&dopt=Abstract
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Final report on the safety assessment of biotin. Author(s): Fiume MZ; Cosmetic Ingredient Review Expert Panel. Source: International Journal of Toxicology. 2001; 20 Suppl 4: 1-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800048&dopt=Abstract
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Fine mapping of the human biotinidase gene and haplotype analysis of five common mutations. Author(s): Blanton SH, Pandya A, Landa BL, Javaheri R, Xia X, Nance WE, Pomponio RJ, Norrgard KJ, Swango KL, Demirkol M, Gulden H, Coskun T, Tokatli A, Ozalp I, Wolf B. Source: Human Heredity. 2000 March-April; 50(2): 102-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799968&dopt=Abstract
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Fluorescence in situ hybridization (FISH) on human chromosomes using photoprobe biotin-labeled probes. Author(s): Weise A, Harbarth P, Claussen U, Liehr T. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 April; 51(4): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642635&dopt=Abstract
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Glyco-western blotting: biotinylated dermatan sulfate as a probe for the detection of dermatan sulfate binding proteins using western blotting. Author(s): Saito A, Munakata H, Satoh K. Source: Connective Tissue Research. 2002; 43(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180264&dopt=Abstract
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HHV-8 ELISA based on a one-step affinity capture of biotinylated K8.1 antigen. Author(s): Juhasz A, Konya J, Beck Z, Remenyik E, Veress G, Begany A, Medgyessy I, Hunyadi J, Gergely L. Source: Journal of Virological Methods. 2001 May; 94(1-2): 163-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337051&dopt=Abstract
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High-performance liquid chromatography coupled to enzyme-amplified biochemical detection for the analysis of hemoglobin after pre-column biotinylation. Author(s): van Bommel MR, de Jong AP, Tjaden UR, Irth H, van der Greef J. Source: J Chromatogr A. 2000 July 21; 886(1-2): 19-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950272&dopt=Abstract
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High-throughput nonradioisotopic determination of binding of platelet-derived growth factor to platelet-derived growth factor receptor beta-extracellular domain using biotinylated ligand with enzyme-linked immunosorbent assay. Author(s): Mahoney CW. Source: Analytical Biochemistry. 1999 December 1; 276(1): 106-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10585751&dopt=Abstract
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Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. Author(s): Solorzano-Vargas RS, Pacheco-Alvarez D, Leon-Del-Rio A. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 April 16; 99(8): 5325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959985&dopt=Abstract
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How biotinylation can interfere with recognition: a surface plasmon resonance study of peptide-antibody interactions. Author(s): Peter JC, Briand JP, Hoebeke J. Source: Journal of Immunological Methods. 2003 March 1; 274(1-2): 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609541&dopt=Abstract
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Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression. Author(s): Obata K, Fukuda T, Morishita R, Abe S, Asakawa S, Yamaguchi S, Yoshino M, Ihara K, Murayama K, Shigemoto K, Shimizu N, Kondo I. Source: Genomics. 2001 March 1; 72(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401427&dopt=Abstract
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Immunohistochemical study of the distribution of endogenous biotin and biotinbinding enzymes in ductal structures of salivary gland tumours. Author(s): Lu CS, Kashima K, Daa T, Yokoyama S, Yanagisawa S, Nakayama I. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2000 October; 29(9): 445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016687&dopt=Abstract
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Immunoprecipitation analysis of pathological autoantibodies in Graves' patients' sera using biotinylated human thyrotropin receptor labeled with 125I-neutravidiny. Author(s): Minich WB, Weymayer JD, Loos U. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 1999; 107(8): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10612487&dopt=Abstract
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Impedimetric immunosensor using avidin-biotin for antibody immobilization. Author(s): Ouerghi O, Touhami A, Jaffrezic-Renault N, Martelet C, Ouada HB, Cosnier S. Source: Bioelectrochemistry (Amsterdam, Netherlands). 2002 May 15; 56(1-2): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009459&dopt=Abstract
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In situ localization of infectious bursal disease virus-binding cells by a biotinstreptavidin system. Author(s): Xue CY, Lim BL. Source: Avian Dis. 2001 April-June; 45(2): 504-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417836&dopt=Abstract
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In vivo biotin supplementation at a pharmacologic dose decreases proliferation rates of human peripheral blood mononuclear cells and cytokine release. Author(s): Zempleni J, Helm RM, Mock DM. Source: The Journal of Nutrition. 2001 May; 131(5): 1479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340103&dopt=Abstract
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In vivo enzymatic protein biotinylation. Author(s): Chapman-Smith A, Cronan JE Jr. Source: Biomolecular Engineering. 1999 December 31; 16(1-4): 119-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796994&dopt=Abstract
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Indicators of marginal biotin deficiency and repletion in humans: validation of 3hydroxyisovaleric acid excretion and a leucine challenge. Author(s): Mock DM, Henrich CL, Carnell N, Mock NI. Source: The American Journal of Clinical Nutrition. 2002 November; 76(5): 1061-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399279&dopt=Abstract
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Inherited defects of biotin metabolism. Author(s): Baumgartner ER, Suormala T. Source: Biofactors (Oxford, England). 1999; 10(2-3): 287-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609895&dopt=Abstract
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Inhibitors of NF-kappaB signaling: design and synthesis of a biotinylated isopanepoxydone affinity reagent. Author(s): Shotwell JB, Koh B, Choi HW, Wood JL, Crews CM. Source: Bioorganic & Medicinal Chemistry Letters. 2002 December 2; 12(23): 3463-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419384&dopt=Abstract
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Interleukin-2 receptor-gamma -dependent endocytosis depends on biotin in Jurkat cells. Author(s): Rodriguez-Melendez R, Camporeale G, Griffin JB, Zempleni J. Source: American Journal of Physiology. Cell Physiology. 2003 February; 284(2): C41521. Epub 2002 October 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388078&dopt=Abstract
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Keratinocytes join forces with immune cells in the prosecution of SMVT as a “false” biotin transporter. Author(s): Prasad PD, Ganapathy V. Source: The Journal of Investigative Dermatology. 2003 March; 120(3): Xi-Xii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603871&dopt=Abstract
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Leishmania antigen nonspecific binding to avidin in biotin-avidin immunoassays. Author(s): Agudelo S, Portus M. Source: Clinical and Diagnostic Laboratory Immunology. 2000 July; 7(4): 717-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991608&dopt=Abstract
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Localization of biotinidase in the brain: implications for its role in hearing loss in biotinidase deficiency. Author(s): Heller AJ, Stanley C, Shaia WT, Sismanis A, Spencer RF, Wolf B. Source: Hearing Research. 2002 November; 173(1-2): 62-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372635&dopt=Abstract
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Low serum biotinidase activity in children with valproic acid monotherapy. Author(s): Schulpis KH, Karikas GA, Tjamouranis J, Regoutas S, Tsakiris S. Source: Epilepsia. 2001 October; 42(10): 1359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737173&dopt=Abstract
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Marginal biotin deficiency during normal pregnancy. Author(s): Mock DM, Quirk JG, Mock NI. Source: The American Journal of Clinical Nutrition. 2002 February; 75(2): 295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815321&dopt=Abstract
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Marginal biotin deficiency is teratogenic. Author(s): Zempleni J, Mock DM. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 2000 January; 223(1): 14-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10632957&dopt=Abstract
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Matrix interference in serum total thyroxin (T4) time-resolved fluorescence immunoassay (TRFIA) and its elimination with the use of streptavidin-biotin separation technique. Author(s): Wu FB, He YF, Han SQ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 June; 308(1-2): 117-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412823&dopt=Abstract
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Metabolic biotinylation of recombinant proteins in mammalian cells and in mice. Author(s): Parrott MB, Barry MA. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2000 January; 1(1): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933917&dopt=Abstract
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Molecular characterisation of 34 patients with biotinidase deficiency ascertained by newborn screening and family investigation. Author(s): Muhl A, Moslinger D, Item CB, Stockler-Ipsiroglu S. Source: European Journal of Human Genetics : Ejhg. 2001 April; 9(4): 237-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313766&dopt=Abstract
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Molecular cloning and characterization of two genes for the biotin carboxylase and carboxyltransferase subunits of acetyl coenzyme A carboxylase in Myxococcus xanthus. Author(s): Kimura Y, Miyake R, Tokumasu Y, Sato M. Source: Journal of Bacteriology. 2000 October; 182(19): 5462-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986250&dopt=Abstract
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Monocarboxylate transporter 1 mediates biotin uptake in human peripheral blood mononuclear cells. Author(s): Daberkow RL, White BR, Cederberg RA, Griffin JB, Zempleni J. Source: The Journal of Nutrition. 2003 September; 133(9): 2703-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949353&dopt=Abstract
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Natural antibodies to nematode biotinyl-enzymes in human sera. Author(s): Lorenzo S, Iglesias R, Paniagua E, Ansotegui I, Alonso JM, Ubeira FM. Source: Medical Microbiology and Immunology. 2001 September; 189(4): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599787&dopt=Abstract
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Novel mutations cause biotinidase deficiency in Turkish children. Author(s): Pomponio RJ, Coskun T, Demirkol M, Tokatli A, Ozalp I, Huner G, Baykal T, Wolf B. Source: Journal of Inherited Metabolic Disease. 2000 March; 23(2): 120-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801053&dopt=Abstract
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Novel mutations in children with profound biotinidase deficiency from Saudi Arabia. Author(s): Pomponio RJ, Ozand PT, Al Essa M, Wolf B. Source: Journal of Inherited Metabolic Disease. 2000 March; 23(2): 185-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801060&dopt=Abstract
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Nuclear run-on assay using biotin labeling, magnetic bead capture and analysis by fluorescence-based RT-PCR. Author(s): Patrone G, Puppo F, Cusano R, Scaranari M, Ceccherini I, Puliti A, Ravazzolo R. Source: Biotechniques. 2000 November; 29(5): 1012-4, 1016-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084863&dopt=Abstract
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Organelle pH studies using targeted avidin and fluorescein-biotin. Author(s): Wu MM, Llopis J, Adams S, McCaffery JM, Kulomaa MS, Machen TE, Moore HP, Tsien RY. Source: Chemistry & Biology. 2000 March; 7(3): 197-209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712929&dopt=Abstract
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Ovarian endometriosis showing decidual change and Arias-Stella reaction with biotin-containing intranuclear inclusions. Author(s): Sakaki M, Hirokawa M, Sano T, Takahashi H, Tezuka K, Abe K, Sano M. Source: Acta Cytol. 2003 March-April; 47(2): 321-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685213&dopt=Abstract
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Pancreatoblastoma. A case report with special emphasis on squamoid corpuscles with optically clear nuclei rich in biotin. Author(s): Hasegawa Y, Ishida Y, Kato K, Ijiri R, Miyake T, Nishimata S, Watanabe T, Namba I, Hayabuchi Y, Kigasawa H, Tanaka Y. Source: Acta Cytol. 2003 July-August; 47(4): 679-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920766&dopt=Abstract
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Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer. Author(s): Guy M, Pons L, Namour F, de Nonancourt M, Michalski JC, Hatier R, Gueant JL. Source: Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2001; 11(5): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684816&dopt=Abstract
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Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer. Author(s): Knox SJ, Goris ML, Tempero M, Weiden PL, Gentner L, Breitz H, Adams GP, Axworthy D, Gaffigan S, Bryan K, Fisher DR, Colcher D, Horak ID, Weiner LM. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 February; 6(2): 406-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690517&dopt=Abstract
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Photochemical control of the infectivity of adenoviral vectors using a novel photocleavable biotinylation reagent. Author(s): Pandori MW, Hobson DA, Olejnik J, Krzymanska-Olejnik E, Rothschild KJ, Palmer AA, Phillips TJ, Sano T. Source: Chemistry & Biology. 2002 May; 9(5): 567-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031663&dopt=Abstract
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Plasma 11beta-hydroxy-4-androstene-3,17-dione: comparison of a time-resolved fluoroimmunoassay using a biotinylated tracer with a radioimmunoassay using a tritiated tracer. Author(s): Ibrahim F, Giton F, Boudou P, Villette JM, Julien R, Galons H, Fiet J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 April; 84(5): 563-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767281&dopt=Abstract
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Plasma 17-OH pregnenolone: comparison of a time-resolved fluoroimmunoassay using a new tracer 17-OH pregnenolone-3-oxyacetyl-biotine with a radioimmunoassay using 125I 17-OH pregnenolone-3-hemisuccinate-histamine. Author(s): Fiet J, Giton F, Boudi A, Boudou P, Soliman H, Villette J, Galons H. Source: Steroids. 2001 February; 66(2): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146086&dopt=Abstract
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Plasma 21-deoxycortisol: comparison of a time-resolved fluoroimmunoassay using a biotinylated tracer with a radioimmunossay using (125)iodine. Author(s): Fiet J, Boudi A, Giton F, Villette JM, Boudou P, Soliman H, Morineau G, Galons H. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2000 JanuaryFebruary; 72(1-2): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731638&dopt=Abstract
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Post-column reaction detection of biotin in human plasma ultrafiltrate based on laserinduced fluorescence energy transfer in the far-red spectral region. Author(s): Shahdeo K, Anderson FP, Karnes HT. Source: Biomedical Chromatography : Bmc. 2000 August; 14(5): 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960830&dopt=Abstract
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Preparation of avidin-labeled protein nanoparticles as carriers for biotinylated peptide nucleic acid. Author(s): Langer K, Coester C, Weber C, von Briesen H, Kreuter J. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 2000 May; 49(3): 3037. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799823&dopt=Abstract
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Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study. Author(s): Grana C, Chinol M, Robertson C, Mazzetta C, Bartolomei M, De Cicco C, Fiorenza M, Gatti M, Caliceti P, Paganelli G. Source: British Journal of Cancer. 2002 January 21; 86(2): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870507&dopt=Abstract
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Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results. Author(s): Paganelli G, Bartolomei M, Ferrari M, Cremonesi M, Broggi G, Maira G, Sturiale C, Grana C, Prisco G, Gatti M, Caliceti P, Chinol M. Source: Cancer Biotherapy & Radiopharmaceuticals. 2001 June; 16(3): 227-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471487&dopt=Abstract
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Pre-targeted radioimmunotherapy of human colon cancer xenografts in athymic mice using streptavidin-CC49 monoclonal antibody and 90Y-DOTA-biotin. Author(s): Domingo RJ, Reilly RM. Source: Nuclear Medicine Communications. 2000 January; 21(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717908&dopt=Abstract
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Radiation absorbed dose estimation for 90Y-DOTA-biotin with pretargeted NR-LU10/streptavidin. Author(s): Breitz HB, Fisher DR, Goris ML, Knox S, Ratliff B, Murtha AD, Weiden PL. Source: Cancer Biotherapy & Radiopharmaceuticals. 1999 October; 14(5): 381-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850323&dopt=Abstract
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Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibodystreptavidin and (90)Y-labeled 1,4,7,10-tetraazacyclododecane-N,N',N”,N”'-tetraacetic acid (DOTA)-biotin. Author(s): Yao Z, Zhang M, Axworthy DB, Wong KJ, Garmestani K, Park L, Park CW, Mallett RW, Theodore LJ, Yau EK, Waldmann TA, Brechbiel MW, Paik CH, Pastan I, Carrasquillo JA. Source: Cancer Research. 2002 October 15; 62(20): 5755-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384535&dopt=Abstract
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Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency. Author(s): Dobrowolski SF, Angeletti J, Banas RA, Naylor EW. Source: Molecular Genetics and Metabolism. 2003 February; 78(2): 100-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618081&dopt=Abstract
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Recombinant NeutraLite avidin: a non-glycosylated, acidic mutant of chicken avidin that exhibits high affinity for biotin and low non-specific binding properties. Author(s): Marttila AT, Laitinen OH, Airenne KJ, Kulik T, Bayer EA, Wilchek M, Kulomaa MS. Source: Febs Letters. 2000 February 4; 467(1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10664451&dopt=Abstract
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Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. Author(s): Sakamoto O, Suzuki Y, Li X, Aoki Y, Hiratsuka M, Suormala T, Baumgartner ER, Gibson KM, Narisawa K. Source: Pediatric Research. 1999 December; 46(6): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10590022&dopt=Abstract
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Reversible deafness caused by biotinidase deficiency. Author(s): Straussberg R, Saiag E, Harel L, Korman SH, Amir J. Source: Pediatric Neurology. 2000 September; 23(3): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033293&dopt=Abstract
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Selection of antibodies against biotinylated antigens. Author(s): Chames P, Hoogenboom HR, Henderikx P. Source: Methods in Molecular Biology (Clifton, N.J.). 2002; 178: 147-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968483&dopt=Abstract
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Selective 'in synthesis' labeling of peptides with biotin and rhodamine. Author(s): Chersi A, Giommi S, Rosano L. Source: Biochimica Et Biophysica Acta. 2000 April 6; 1474(2): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10742599&dopt=Abstract
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Serum biotinidase activity in children with chronic liver disease and its clinical significance. Author(s): Pabuccuoglu A, Aydogdu S, Bas M. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 January; 34(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753166&dopt=Abstract
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Seventeen novel mutations that cause profound biotinidase deficiency. Author(s): Wolf B, Jensen K, Huner G, Demirkol M, Baykal T, Divry P, Rolland MO, Perez-Cerda C, Ugarte M, Straussberg R, Basel-Vanagaite L, Baumgartner ER, Suormala T, Scholl S, Das AM, Schweitzer S, Pronicka E, Sykut-Cegielska J. Source: Molecular Genetics and Metabolism. 2002 September-October; 77(1-2): 108-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359137&dopt=Abstract
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Signal amplification in flow cytometry using biotin tyramine. Author(s): Earnshaw JC, Osbourn JK. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1999 February 1; 35(2): 176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554174&dopt=Abstract
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Simple purification of highly active biotinylated P-glycoprotein: enantiomer-specific modulation of drug-stimulated ATPase activity. Author(s): Julien M, Kajiji S, Kaback RH, Gros P. Source: Biochemistry. 2000 January 11; 39(1): 75-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10625481&dopt=Abstract
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Simplification of complex peptide mixtures for proteomic analysis: reversible biotinylation of cysteinyl peptides. Author(s): Spahr CS, Susin SA, Bures EJ, Robinson JH, Davis MT, McGinley MD, Kroemer G, Patterson SD. Source: Electrophoresis. 2000 May; 21(9): 1635-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870950&dopt=Abstract
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Single nucleotide polymorphism detection by combinatorial fluorescence energy transfer tags and biotinylated dideoxynucleotides. Author(s): Tong AK, Ju J. Source: Nucleic Acids Research. 2002 March 1; 30(5): E19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861924&dopt=Abstract
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Streptabody, a high avidity molecule made by tetramerization of in vivo biotinylated, phage display-selected scFv fragments on streptavidin. Author(s): Cloutier SM, Couty S, Terskikh A, Marguerat L, Crivelli V, Pugnieres M, Mani JC, Leisinger HJ, Mach JP, Deperthes D. Source: Molecular Immunology. 2000 December; 37(17): 1067-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399324&dopt=Abstract
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Structural and biosensor analyses of a synthetic biotinylated peptide probe for the isolation of adenomatous polyposis coli tumor suppressor protein complexes. Author(s): Wade JD, Catimel B, Faux MC, Burgess AW, Nice E, Otvos L Jr. Source: The Journal of Peptide Research : Official Journal of the American Peptide Society. 2001 September; 58(3): 204-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576326&dopt=Abstract
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Studying organelle physiology with fusion protein-targeted avidin and fluorescent biotin conjugates. Author(s): Wu MM, Llopis J, Adams SR, McCaffery JM, Teter K, Kulomaa MS, Machen TE, Moore HP, Tsien RY. Source: Methods Enzymol. 2000; 327: 546-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045008&dopt=Abstract
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Surface membrane biotinylation efficiently mediates the endocytosis of avidin bioconjugates into nucleated cells. Author(s): Wojda U, Goldsmith P, Miller JL. Source: Bioconjugate Chemistry. 1999 November-December; 10(6): 1044-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563774&dopt=Abstract
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Synthesis and biological characterization of sqbazide, a novel biotinylated photoaffinity probe for the study of the human platelet thromboxane A2 receptor. Author(s): Halmos T, Turek JW, Le Breton GC, Antonakis K. Source: Bioorganic & Medicinal Chemistry Letters. 1999 October 18; 9(20): 2963-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571156&dopt=Abstract
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Synthesis and NKT cell stimulating properties of fluorophore- and biotin-appended 6”-amino-6”-deoxy-galactosylceramides. Author(s): Zhou XT, Forestier C, Goff RD, Li C, Teyton L, Bendelac A, Savage PB. Source: Organic Letters. 2002 April 18; 4(8): 1267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950339&dopt=Abstract
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Synthesis of biotinylated bis(D-glucose) derivatives for glucose transporter photoaffinity labelling. Author(s): Hashimoto M, Hatanaka Y, Yang J, Dhesi J, Holman GD. Source: Carbohydrate Research. 2001 March 22; 331(2): 119-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322726&dopt=Abstract
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The biotin enzyme family: conserved structural motifs and domain rearrangements. Author(s): Jitrapakdee S, Wallace JC. Source: Current Protein & Peptide Science. 2003 June; 4(3): 217-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769720&dopt=Abstract
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The biotin switch method for the detection of S-nitrosylated proteins. Author(s): Jaffrey SR, Snyder SH. Source: Science's Stke [electronic Resource] : Signal Transduction Knowledge Environment. 2001 June 12; 2001(86): Pl1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752655&dopt=Abstract
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The enhanced reactivity of endogenous biotin-like molecules by antigen retrieval procedures and signal amplification with tyramine. Author(s): Kim SH, Jung KC, Shin YK, Lee KM, Park YS, Choi YL, Oh KI, Kim MK, Chung DH, Son HG, Park SH. Source: The Histochemical Journal. 2002 March-April; 34(3-4): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495214&dopt=Abstract
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The immunohistochemical detection of mismatch repair gene proteins (MLH1, MSH2, MSH6, and PMS2): practical aspects in antigen retrieval and biotin blocking protocols. Author(s): Manavis J, Gilham P, Davies R, Ruszkiewicz A. Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication of the Society for Applied Immunohistochemistry. 2003 March; 11(1): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610360&dopt=Abstract
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The use of an in-house biotin-avidin linked immunosorbent assay to detect Aspergillus antigens in sera of immunocompromised patients. Author(s): Abdul Samad S, Yusoff H, Fadilah SA. Source: Med J Malaysia. 2001 March; 56(1): 32-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503293&dopt=Abstract
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Transport of biotin in human keratinocytes. Author(s): Grafe F, Wohlrab W, Neubert RH, Brandsch M. Source: The Journal of Investigative Dermatology. 2003 March; 120(3): 428-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603856&dopt=Abstract
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Trifunctional conjugation reagents. Reagents that contain a biotin and a radiometal chelation moiety for application to extracorporeal affinity adsorption of radiolabeled antibodies. Author(s): Wilbur DS, Chyan MK, Hamlin DK, Kegley BB, Nilsson R, Sandberg BE, Brechbiel M. Source: Bioconjugate Chemistry. 2002 September-October; 13(5): 1079-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236790&dopt=Abstract
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Tyramide signal amplification of biotinylated probe in dot-blot hybridization assay for the detection of parvovirus B19 DNA in serum samples. Author(s): Zerbini M, Cricca M, Gentilomi G, Venturoli S, Gallinella G, Musiani M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2000 December; 302(1-2): 79-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074066&dopt=Abstract
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Utilization of biotin in proliferating human lymphocytes. Author(s): Zempleni J, Mock DM. Source: The Journal of Nutrition. 2000 February; 130(2S Suppl): 335S-337S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721900&dopt=Abstract
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CHAPTER 2. NUTRITION AND BIOTIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and biotin.
Finding Nutrition Studies on Biotin 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 “biotin” (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 is a typical result when searching for recently indexed consumer information on biotin: •
Beauty in a pill: are supplements today's fountain of youth? Source: Hughes, L. Environmental-nutrition (USA). (March 1996). volume 19(3) page 1, 4-5.
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The nutritional importance of biotin: an update. Source: Marshall, M.W. Nutrition-today (USA). (December 1987). volume 22(6) page 2630.
Additional consumer oriented references include: •
A role for biotin in bone growth. Source: Anonymous Nutr-Revolume 1989 May; 47(5): 157-9 0029-6643
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Biotin biotin biotin biotin. Source: Papazian, R. FDA-Consum. Rockville, Md. : Food and Drug Administration, Department of Health & Human Services. October 1991. volume 25 (8) page 34-35. 03621332
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Biotin homeostasis during the cell cycle. Source: Zempleni, J. Mock, D.M. Nutr-res-rev. Wallingford, Oxon, U.K. : CAB International. June 2001. volume 14 (1) page 45-63. 0954-4224
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Biotin in animal nutrition. Source: Anonymous Nutr-Revolume 1990 September; 48(9): 352-5 0029-6643
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The B vitamins: Folic acid and biotin. Source: Metcalfe, Jill. Nutr-Food-Sci. London, Nov/December 1982. (79) page 15-17. 0034-6659
Eng.
:
Forbes
Publications.
The following information is typical of that found when using the “Full IBIDS Database” to search for “biotin” (or a synonym): •
Effect of foliar application of biotin and pix on the growth and chemical composition of Bulgarian peppermint produced under Egyptian local conditions. Author(s): National Research Center, Cairo (Egypt). Culture and Production of Medicen and Aromatic plants Dept. Source: Youssef, A.A. Moussa, Z.A. Mansoura-University-Journal-of-AgriculturalSciences (Egypt). (May 2001). volume 26 (5) page 3331-3340. Received 2002.
Additional physician-oriented references include: •
A receptor-mediated gene delivery system using streptavidin and biotin-derivatized, pegylated epidermal growth factor. Author(s): Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea. Source: Lee, H Kim, T H Park, T G J-Control-Release. 2002 September 18; 83(1): 109-19 0168-3659
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A streptavidin-biotin binding system that minimizes blocking by endogenous biotin. Author(s): Department of Bioengineering, University of Washington, Seattle 98195, USA.
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Source: Hamblett, K J Kegley, B B Hamlin, D K Chyan, M K Hyre, D E Press, O W Wilbur, D S Stayton, P S Bioconjug-Chem. 2002 May-June; 13(3): 588-98 1043-1802 •
An improved protocol of biotinylated tyramine-based immunohistochemistry minimizing nonspecific background staining. Author(s): Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
[email protected] Source: Kim, S H Shin, Y K Lee, K M Lee, J S Yun, J H Lee, S M J-Histochem-Cytochem. 2003 January; 51(1): 129-32 0022-1554
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An innovative strategy for immobilization of receptor proteins on to an optical fiber by use of poly(pyrrole-biotin). Author(s): Department of Biotechnology Engineering Ben-Gurion University of the Negev, PO Box 653, Beer-Sheva 84105, Israel.
[email protected] Source: Marks, R S Novoa, A Thomassey, D Cosnier, S Anal-Bioanal-Chem. 2002 Nov; 374(6): 1056-63 1618-2642
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Binding specificity and the ligand dissociation process in the E. coli biotin holoenzyme synthetase. Author(s): Department of Chemistry and Biochemistry, College of Life Sciences, University of Maryland, College Park, Maryland 20472, USA. Source: Kwon, K Streaker, E D Beckett, D Protein-Sci. 2002 March; 11(3): 558-70 09618368
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Coupling of protein assembly and DNA binding: biotin repressor dimerization precedes biotin operator binding. Author(s): Department of Chemistry and Biochemistry, College of Life Sciences, University of Maryland, College Park, MD 20742-2021, USA. Source: Streaker, E D Beckett, D J-Mol-Biol. 2003 January 31; 325(5): 937-48 0022-2836
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Design, production, and characterization of an engineered biotin ligase (BirA) and its application for affinity purification of staphylokinase produced from Bacillus subtilis via secretion. Author(s): Department of Biological Sciences, Division of Cellular, Molecular, and Microbial Biology, University of Calgary, 2500 University Drive, N.W., Calgary, Alberta T2N 1N4, Canada. Source: Wu, S C Yeung, J C Hwang, P M Wong, S L Protein-Expr-Purif. 2002 April; 24(3): 357-65 1046-5928
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Dissecting streptavidin-biotin interaction with a laminar flow chamber. Author(s): Laboratoire d'Immunologie, INSERM U 387, Hopital Ste-Marguerite, BP 29, 13274 Marseille Cedex 09, France. Source: Pierres, A Touchard, D Benoliel, A M Bongrand, P Biophys-J. 2002 June; 82(6): 3214-23 0006-3495
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DNA-directed assembly of bienzymic complexes from in vivo biotinylated NAD(P)H:FMN oxidoreductase and luciferase. Author(s): Universitat Bremen, FB2-UFT Biotechnologie und Molekulare Genetik, Leobener Strasse, 28359 Bremen, Germany.
[email protected] Source: Niemeyer, Christof M Koehler, Joerg Wuerdemann, Chris Chembiochem. 2002 March 1; 3(2-3): 242-5 1439-4227
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Early mechanistic events in biotin dissociation from streptavidin. Author(s): Department of Bioengineering, University of Washington, Washington 98195, USA.
Seattle,
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Source: Hyre, David E Amon, Lynn M Penzotti, Julie E Le Trong, Isolde Stenkamp, Ronald E Lybrand, Terry P Stayton, Patrick S Nat-Struct-Biol. 2002 August; 9(8): 582-5 1072-8368 •
Impedimetric immunosensor using avidin-biotin for antibody immobilization. Author(s): Ingenierie et Fonctionnalisation des Surfaces, UMR CNRS 5621, Ecole Centrale de Lyon, BP 163, F-69131 Ecully Cedex, France. Source: Ouerghi, O Touhami, A Jaffrezic Renault, N Martelet, C Ouada, H B Cosnier, S Bioelectrochemistry. 2002 May 15; 56(1-2): 131-3 1567-5394
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Isoserine-based biotinylated photoaffinity probes that interact with penicillinbinding protein 1b. Author(s): Institut fur Organische Chemie, Universitat Leipzig, Johannisalle 29, D-04103 Leipzig, Germany. Source: Ruhl, T Volke, D Stembera, K Hatanaka, Y Hennig, H Schumer, F Welzel, P Chem-Commun-(Camb). 2002 August 7; (15): 1630-1 1359-7345
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Multivalent interactions between biotin-polyrotaxane conjugates and streptavidin as a model of new targeting for transporters. Author(s): School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan. Source: Ooya, Tooru Yui, Nobuhiko J-Control-Release. 2002 April 23; 80(1-3): 219-28 0168-3659
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Photochemical control of the infectivity of adenoviral vectors using a novel photocleavable biotinylation reagent. Author(s): Center for Molecular Imaging Diagnosis and Therapy and Basic Science Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Source: Pandori, M W Hobson, D A Olejnik, J Krzymanska Olejnik, E Rothschild, K J Palmer, A A Phillips, T J Sano, T Chem-Biol. 2002 May; 9(5): 567-73 1074-5521
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Selection of antibodies against biotinylated antigens. Author(s): Department of Pathology, Maastricht University and University Hospital, Maastricht, The Netherlands. Source: Chames, P Hoogenboom, H R Henderikx, P Methods-Mol-Biol. 2002; 178: 147-57 1064-3745
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Sensitivity studies for specific binding reactions using the biotin/streptavidin system by evanescent optical methods. Author(s): Max-Planck-Institut fur Polymerforschung, Ackermann Weg 10, 55128, Mainz, Germany. Source: Busse, S Scheumann, V Menges, B Mittler, S Biosens-Bioelectron. 2002 August; 17(8): 704-10 0956-5663
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Streptavidin in antibody pretargeting. 3. Comparison of biotin binding and tissue localization of 1,2-cyclohexanedione and succinic anhydride modified recombinant streptavidin. Author(s): Department of Radiation Oncology, University of Washington, Seattle 98195, USA.
[email protected] Source: Wilbur, D S Hamlin, D K Meyer, D L Mallett, R W Quinn, J Vessella, R L Press, O W Bioconjug-Chem. 2002 May-June; 13(3): 611-20 1043-1802
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Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified poly-L-lysine: evaluation for use as an effector molecule in pretargeted intraperitoneal tumor therapy. Author(s): Department of Radiation Physics, Goteborg University, Sahlgrenska University Hospital, SE-413 45, Sweden.
[email protected] Source: Lindegren, S Andersson, H Jacobsson, L Back, T Skarnemark, G Karlsson, B Bioconjug-Chem. 2002 May-June; 13(3): 502-9 1043-1802
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Synthesis and characterisation of a degradable poly(lactic acid)-poly(ethylene glycol) copolymer with biotinylated end groups. Author(s): School of Pharmaceutical Sciences, University of Nottingham, Nottingham, NG7 2RD, U.K. Source: Salem, A K Cannizzaro, S M Davies, M C Tendler, S J Roberts, C J Williams, P M Shakesheff, K M Biomacromolecules. 2001 Summer; 2(2): 575-80 1525-7797
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Synthesis of biotin conjugates of the antifungal compound cymoxanil. Author(s): Rohm and Haas Co, PO Box 904, 727 Norristown Road, Spring House, PA 19477-0904, USA. Source: Evans, K A Kane, C T Tice, C M Pest-Manag-Sci. 2002 April; 58(4): 392-6 1526498X
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The effect of an agglutogen on virus infection: biotinylated filamentous phages and avidin as a model. Author(s): Department of Anatomy and Cell Biology, School of Medicine, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
[email protected] Source: Nakamura, Michihiro Tsumoto, Kouhei Ishimura, Kazunori Kumagai, Izumi FEBS-Lett. 2002 June 5; 520(1-3): 77-80 0014-5793
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The PLP-dependent biotin synthase from Escherichia coli: mechanistic studies. Author(s): Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, DRDCCB, CEA/CNRS/Universite Joseph Fourier, UMR 5047, 17 Avenue des Martyrs, 38054 Cedex 09, Grenoble, France Source: Ollagnier de Choudens, S Mulliez, E Fontecave, M FEBS-Lett. 2002 December 18; 532(3): 465-8 0014-5793
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Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis. Author(s): Laboratoire de Chimie Organique Biologique, Universite Paris VI, UMR CNRS 7613, France. Source: Mann, Stephane Carillon, Sophie Breyne, Olivier Marquet, Andree Chemistry. 2002 January 18; 8(2): 439-50 0947-6539
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Tracing of projection neurons from the cervical dorsal horn to the medulla with the anterograde tracer biotinylated dextran amine. Author(s): Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
[email protected] Source: Potts, J T Lee, S M Anguelov, P I Auton-Neurosci. 2002 June 28; 98(1-2): 64-9 1566-0702
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Transition metal-carbonyl labeling of biotin and avidin for use in solid-phase carbonyl metallo immunoassay (CMIA). Author(s): Ecole Nationale Superieure de Chimie de Paris, Laboratoire de Chimie et Biochimie des Complexes Moleculaires (UMR CNRS 7576), 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France. Source: Salmain, M Fischer Durand, N Cavalier, L Rudolf, B Zakrzewski, J Jaouen, G Bioconjug-Chem. 2002 May-June; 13(3): 693-8 1043-1802
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Visualisation of hyaluronan and hyaluronan-binding proteins within ovine vertebral cartilages using biotinylated aggrecan G1-link complex and biotinylated hyaluronan oligosaccharides. Author(s): The Institute of Bone and Joint Research, The University of Sydney, Department of Surgery, Royal North Shore Hospital of Sydney, St. Leonards, NSW, Australia.
[email protected] Source: Melrose, J Tammi, M Smith, S Histochem-Cell-Biol. 2002 April; 117(4): 327-33 0948-6143
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/
Nutrition
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to biotin; 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: •
Vitamins Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Multiple Vitamin-mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Complex Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,962,00.html Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B-Complex Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Biotin Source: Healthnotes, Inc.; www.healthnotes.com Biotin Alternative names: Vitamin H (Biotin) Source: Integrative Medicine Communications; www.drkoop.com Biotin Source: Prima Communications, Inc.www.personalhealthzone.com Biotin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10008,00.html
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Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Sulfur Source: Healthnotes, Inc.; www.healthnotes.com Vitamin H (Biotin) Alternative names: Biotin Source: Integrative Medicine Communications; www.drkoop.com •
Food and Diet Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND BIOTIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to biotin. 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 biotin 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 “biotin” (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 biotin: •
A method of combining biocytin tract-tracing with avidin-biotin-peroxidase complex immunocytochemistry for pre-embedding electron microscopic labeling in neonatal tissue. Author(s): Erisir A, Aoki C. Source: Journal of Neuroscience Methods. 1998 June 1; 81(1-2): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uid s=9696325&dopt=Abstract
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A microtiter assay for factor XIII using fibrinogen and biotinylcadaverine as substrates. Author(s): Song YC, Sheng D, Taubenfeld SM, Matsueda GR. Source: Analytical Biochemistry. 1994 November 15; 223(1): 88-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7695107&dopt=Abstract
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Abnormal fatty acid composition of lymphocytes of biotin-deficient rats. Author(s): Liu YY, Shigematsu Y, Bykov I, Nakai A, Kikawa Y, Fukui T, Sudo M.
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Source: J Nutr Sci Vitaminol (Tokyo). 1994 June; 40(3): 283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7965217&dopt=Abstract •
Acetyl coenzyme A carboxylase system of Escherichia coli. Studies on the mechanisms of the biotin carboxylase- and carboxyltransferase-catalyzed reactions. Author(s): Polakis SE, Guchhait RB, Zwergel EE, Lane MD, Cooper TG. Source: The Journal of Biological Chemistry. 1974 October 25; 249(20): 6657-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4154091&dopt=Abstract
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Acylcarnitine profile in tissues and body fluids of biotin-deficient rats with and without L-carnitine supplementation. Author(s): Shigematsu Y, Bykov IL, Liu YY, Nakai A, Kikawa Y, Sudo M, Fujioka M. Source: Journal of Inherited Metabolic Disease. 1994; 17(6): 678-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7707691&dopt=Abstract
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An automated biotin-streptavidin procedure for progesterone evaluation. Author(s): Pesce MA, Bodourian SH, Sheehan M, Henkel CF. Source: Clinical Biochemistry. 1992 December; 25(6): 451-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1477970&dopt=Abstract
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An enzyme immunoassay for prostaglandin E2 using biotin-prostaglandin B2 conjugate as a tracer. Author(s): Watanabe S, Yoshida C, Kobayashi T, Okuyama H. Source: Biological & Pharmaceutical Bulletin. 1997 January; 20(1): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013819&dopt=Abstract
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Application of biotin, digoxigenin or fluorescein conjugated deoxynucleotides to label DNA strand breaks for analysis of cell proliferation and apoptosis using flow cytometry. Author(s): Li X, James WM, Traganos F, Darzynkiewicz Z. Source: Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission. 1995 September; 70(5): 234-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8580207&dopt=Abstract
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Are patients with chronic renal failure (CRF) deficient in Biotin and is regular Biotin supplementation required? Author(s): Jung U, Helbich-Endermann M, Bitsch R, Schneider S, Stein G. Source: Zeitschrift Fur Ernahrungswissenschaft. 1998 December; 37(4): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894686&dopt=Abstract
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Biological properties of biotin-chelate conjugates for pretargeted diagnosis and therapy with the avidin/biotin system. Author(s): Goodwin DA, Meares CF, Osen M.
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Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1998 October; 39(10): 1813-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9776294&dopt=Abstract •
Biosynthesis of biotin-vitamers from unsaturated higher fatty acids by bacteria. Author(s): Ohsugi M, Miyauchi K, Inoue Y. Source: J Nutr Sci Vitaminol (Tokyo). 1985 June; 31(3): 253-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2866239&dopt=Abstract
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Biotin deficiency in an infant fed with amino acid formula and hypoallergenic rice. Author(s): Higuchi R, Noda E, Koyama Y, Shirai T, Horino A, Juri T, Koike M. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 July; 85(7): 872-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8819558&dopt=Abstract
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Biotin nutritional status of vegans, lactoovovegetarians, and nonvegetarians. Author(s): Lombard KA, Mock DM. Source: The American Journal of Clinical Nutrition. 1989 September; 50(3): 486-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2773827&dopt=Abstract
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Biotin- or digoxigenin-conjugated nucleotides bind to matrix vesicles in atherosclerotic plaques. Author(s): Kockx MM, Muhring J, Bortier H, De Meyer GR, Jacob W. Source: American Journal of Pathology. 1996 June; 148(6): 1771-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8669464&dopt=Abstract
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Biotin supplementation affects lymphocyte carboxylases and plasma biotin in severe protein-energy malnutrition. Author(s): Velazquez A, Teran M, Baez A, Gutierrez J, Rodriguez R. Source: The American Journal of Clinical Nutrition. 1995 February; 61(2): 385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7840079&dopt=Abstract
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Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice. Author(s): Reddi A, DeAngelis B, Frank O, Lasker N, Baker H. Source: Life Sciences. 1988; 42(13): 1323-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3280936&dopt=Abstract
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Biotin supplementation in greasy pig disease. Author(s): Gillespie TG. Source: Mod Vet Pract. 1982 September; 63(9): 724-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7188283&dopt=Abstract
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Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase, and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells. Author(s): Wiedmann S, Eudy JD, Zempleni J. Source: The Journal of Nutrition. 2003 March; 133(3): 716-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612142&dopt=Abstract
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Biotin supplementation of practical diets for channel catfish. Author(s): Lovell RT, Buston JC. Source: The Journal of Nutrition. 1984 June; 114(6): 1092-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6726471&dopt=Abstract
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Biotin-supplementation of diets; the incidence of foot lesions, and the reproductive performance of sows. Author(s): Brooks PH, Smith DA, Irwin VC. Source: The Veterinary Record. 1977 July 16; 101(3): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=888322&dopt=Abstract
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Biotinylation and assessment of membrane polarity: caveats and methodological concerns. Author(s): Gottardi CJ, Dunbar LA, Caplan MJ. Source: The American Journal of Physiology. 1995 February; 268(2 Pt 2): F285-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7864168&dopt=Abstract
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Brittle nails: response to daily biotin supplementation. Author(s): Hochman LG, Scher RK, Meyerson MS. Source: Cutis; Cutaneous Medicine for the Practitioner. 1993 April; 51(4): 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8477615&dopt=Abstract
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Clinical observations on the response of equine hoof defects to dietary supplementation with biotin. Author(s): Comben N, Clark RJ, Sutherland DJ. Source: The Veterinary Record. 1984 December 22-29; 115(25-26): 642-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6523712&dopt=Abstract
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Developmental patterns of free and protein-bound biotin during maturation and germination of seeds of Pisum sativum: characterization of a novel seed-specific biotinylated protein. Author(s): Duval M, Job C, Alban C, Douce R, Job D. Source: The Biochemical Journal. 1994 April 1; 299 ( Pt 1): 141-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8166632&dopt=Abstract
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Dietary biotin effects on polyunsaturated fatty acids in chick tissue lipids and prostaglandin E2 levels in freeze-clamped hearts. Author(s): Watkins BA, Kratzer FH. Source: Poultry Science. 1987 November; 66(11): 1818-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3482130&dopt=Abstract
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Double lectin and immunolabelling for transmission electron microscopy: pre- and post-embedding application using the biotin-streptavidin system and colloidal goldsilver staining. Author(s): Pettitt JM, Humphris DC. Source: The Histochemical Journal. 1991 January; 23(1): 29-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1718928&dopt=Abstract
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Dual staining of lymphocyte membrane antigens with colloidal gold and biotinylated horseradish peroxidase. Author(s): Gibson CE, Penttila IA, Leong AS, Milios J, Zola H, LaBrooy JT. Source: Journal of Immunological Methods. 1994 January 3; 167(1-2): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7508481&dopt=Abstract
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Effect of a dietary supplement of biotin on pig hoof horn strength and hardness. Author(s): Webb NG, Penny RH, Johnston AM. Source: The Veterinary Record. 1984 February 25; 114(8): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6710832&dopt=Abstract
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Effect of biotin deficiency and supplementation on lipid metabolism in rats: cholesterol and lipoproteins. Author(s): Suchy SF, Wolf B. Source: The American Journal of Clinical Nutrition. 1986 May; 43(5): 831-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2871749&dopt=Abstract
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Effect of biotin deficiency and supplementation on lipid metabolism in rats: saturated fatty acids. Author(s): Suchy SF, Rizzo WB, Wolf B. Source: The American Journal of Clinical Nutrition. 1986 October; 44(4): 475-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766434&dopt=Abstract
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Effect of biotin deficiency on the catabolism of linoleate in the rat. Author(s): Travis S, Mathias MM, Dupont J. Source: The Journal of Nutrition. 1972 June; 102(6): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5028671&dopt=Abstract
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Effect of biotin supplementation of a barley-wheat diet on restoration of healthy feet, legs and skin of biotin deficient sows. Author(s): Misir R, Blair R. Source: Research in Veterinary Science. 1986 March; 40(2): 212-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3704339&dopt=Abstract
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Effect of biotin supplementation on incidence of acute death syndrome in broiler chickens. Author(s): Steele P, Edgar J, Doncon G. Source: Poultry Science. 1982 May; 61(5): 909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7100072&dopt=Abstract
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Effect of dietary biotin and lipid on growth, stamina, lipid metabolism and biotincontaining enzymes in brook trout (Salvelinus fontinalis). Author(s): Poston HA, McCartney TH. Source: The Journal of Nutrition. 1974 March; 104(3): 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4811981&dopt=Abstract
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Effect of dietary biotin supplement on equine hoof horn growth rate and hardness. Author(s): Buffa EA, Van Den Berg SS, Verstraete FJ, Swart NG. Source: Equine Veterinary Journal. 1992 November; 24(6): 472-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1459062&dopt=Abstract
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Effect of dietary biotin supplementation on sow reproductive performance and soundness and pig growth and mortality. Author(s): Watkins KL, Southern LL, Miller JE. Source: Journal of Animal Science. 1991 January; 69(1): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2005014&dopt=Abstract
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Effect of essential fatty acid deficiency and type of dietary fat supplementation on biotin-deficient chicks. Author(s): Roland DA Sr, Edwards HM Jr. Source: The Journal of Nutrition. 1971 June; 101(6): 811-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5578927&dopt=Abstract
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Effects of biotin deficiency on polyunsaturated fatty acid metabolism in rats. Author(s): Kramer TR, Briske-Anderson M, Johnson SB, Holman RT. Source: The Journal of Nutrition. 1984 November; 114(11): 2047-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6436451&dopt=Abstract
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Effects of biotin supplementation on performance and claw lesions on a commercial dairy farm. Author(s): Bergsten C, Greenough PR, Gay JM, Seymour WM, Gay CC.
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Source: Journal of Dairy Science. 2003 December; 86(12): 3953-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14740832&dopt=Abstract •
Effects of season, dietary protein supplement and biotin on performance and pyruvate carboxylase activity in livers of poults. Author(s): Atwal AS, Robblee AR, Milligan LP. Source: Poultry Science. 1972 November; 51(6): 2074-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4676761&dopt=Abstract
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Eicosanoic fatty acid reduction in the tibiotarsus of biotin-deficient chicks. Author(s): Watkins BA, Bain SD, Newbrey JW. Source: Calcified Tissue International. 1989 July; 45(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2504463&dopt=Abstract
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Enhancement of TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method using mung bean nuclease, a single-stranded DNA digestion enzyme. Author(s): Umemura S, Yasuda M, Osamura RY, Kawarada Y, Sugiyama T, Tsutsumi Y. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1996 February; 44(2): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8609368&dopt=Abstract
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Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells. Author(s): Minko T, Paranjpe PV, Qiu B, Lalloo A, Won R, Stein S, Sinko PJ. Source: Cancer Chemotherapy and Pharmacology. 2002 August; 50(2): 143-50. Epub 2002 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172980&dopt=Abstract
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Fast lysis by complement and uptake by liver of avidin-carrying biotinylated erythrocytes. Author(s): Muzykantov VR, Seregina N, Smirnov MD. Source: Int J Artif Organs. 1992 October; 15(10): 622-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1428212&dopt=Abstract
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Field experience with d-biotin supplementation to gilt and sow feeds. Author(s): de Jong MF, Sytsema JR. Source: Vet Q. 1983; 5(2): 58-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6880004&dopt=Abstract
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Fluorescent and biotinylated analogues of docetaxel: synthesis and biological evaluation. Author(s): Dubois J, Le Goff MT, Gueritte-Voegelein F, Guenard D, Tollon Y, Wright M.
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Foot rot of pigs: the influence of biotin supplementation on foot lesions in sows. Author(s): Penny RH, Cameron RD, Johnson S, Kenyon PJ, Smith HA, Bell AW, Cole JP, Taylor J. Source: The Veterinary Record. 1980 October 11; 107(15): 350-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7210437&dopt=Abstract
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GABA axons in synaptic contact with dopamine neurons in the substantia nigra: double immunocytochemistry with biotin-peroxidase and protein A-colloidal gold. Author(s): van den Pol AN, Smith AD, Powell JF. Source: Brain Research. 1985 November 25; 348(1): 146-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2866017&dopt=Abstract
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High-dose biotin may down-regulate hepatic expression of acute phase reactants by mimicking the physiological role of nitric oxide. Author(s): McCarty MF. Source: Medical Hypotheses. 2003 October; 61(4): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679004&dopt=Abstract
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High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes. Author(s): McCarty MF. Source: Medical Hypotheses. 1999 May; 52(5): 401-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416947&dopt=Abstract
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Imaging of endosome fusion in BHK fibroblasts based on a novel fluorimetric avidin-biotin binding assay. Author(s): Emans N, Biwersi J, Verkman AS. Source: Biophysical Journal. 1995 August; 69(2): 716-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8527685&dopt=Abstract
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Improved biotinylation of glucose-6-phosphate dehydrogenase using active-siteblocking agents. Author(s): Schray KJ, Gergits F 3rd, Niedbala RS. Source: Analytical Biochemistry. 1985 August 15; 149(1): 225-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4073478&dopt=Abstract
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In vivo biotin supplementation at a pharmacologic dose decreases proliferation rates of human peripheral blood mononuclear cells and cytokine release. Author(s): Zempleni J, Helm RM, Mock DM.
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Source: The Journal of Nutrition. 2001 May; 131(5): 1479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340103&dopt=Abstract •
Increased plasma biotinidase activity in patients with glycogen storage disease type Ia: effect of biotin supplementation. Author(s): Burlina AB, Dermikol M, Mantau A, Piovan S, Grazian L, Zacchello F, Shin Y. Source: Journal of Inherited Metabolic Disease. 1996; 19(2): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8739967&dopt=Abstract
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Influence of biotin supplementation on pig claw horn: a scanning electron microscopic study. Author(s): Kempson SA, Currie RJ, Johnston AM. Source: The Veterinary Record. 1989 January 14; 124(2): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2916313&dopt=Abstract
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INfluence of biotin supplementation on sow reproductive efficiency. Author(s): Penny RH, Cameron RD, Johnson S, Kenyon PJ, Smith HA, Bell AW, Cole JP, Taylor J. Source: The Veterinary Record. 1981 July 25; 109(4): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7292937&dopt=Abstract
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Influence of endogenous biotin on the biodistribution of labelled biotin derivatives in mice. Author(s): Rusckowski M, Fogarasi M, Virzi F, Hnatowich DJ. Source: Nuclear Medicine Communications. 1995 January; 16(1): 38-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7609933&dopt=Abstract
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Influence of wet litter and supplemental biotin on foot pad dermatitis in turkey poults. Author(s): Harms RH, Simpson CF. Source: Poultry Science. 1977 November; 56(6): 2009-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=611499&dopt=Abstract
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Influences of biotin deficiency and dietary trans-fatty acids on tissue lipids in chickens. Author(s): Watkins BA. Source: The British Journal of Nutrition. 1989 January; 61(1): 99-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2923859&dopt=Abstract
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Interleukin-2 receptor-gamma -dependent endocytosis depends on biotin in Jurkat cells. Author(s): Rodriguez-Melendez R, Camporeale G, Griffin JB, Zempleni J.
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Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Purification and characterization of the pimeloyl-CoA synthase, and uptake of pimelate. Author(s): Ploux O, Soularue P, Marquet A, Gloeckler R, Lemoine Y. Source: The Biochemical Journal. 1992 November 1; 287 ( Pt 3): 685-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1445232&dopt=Abstract
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Kinase assay based on thiophosphorylation and biotinylation. Author(s): Jeong S, Nikiforov TT. Source: Biotechniques. 1999 December; 27(6): 1232-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631503&dopt=Abstract
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Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. Author(s): Zempleni J, Trusty TA, Mock DM. Source: The Journal of Nutrition. 1997 September; 127(9): 1776-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9278559&dopt=Abstract
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Localization of free and bound biotin in cells from green pea leaves. Author(s): Baldet P, Alban C, Axiotis S, Douce R. Source: Archives of Biochemistry and Biophysics. 1993 May 15; 303(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8489267&dopt=Abstract
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Localization of infection using streptavidin and biotin: an alternative to nonspecific polyclonal immunoglobulin. Author(s): Rusckowski M, Fritz B, Hnatowich DJ. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1992 October; 33(10): 1810-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1403148&dopt=Abstract
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Locus of action of acetyl CoA in the biotin-carboxylation reaction of pyruvate carboxylase. Author(s): Attwood PV. Source: Biochemistry. 1993 November 30; 32(47): 12736-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8251494&dopt=Abstract
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Marginal biotin deficiency is teratogenic. Author(s): Zempleni J, Mock DM.
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Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. Author(s): Burri BJ, Sweetman L, Nyhan WL. Source: The Journal of Clinical Investigation. 1981 December; 68(6): 1491-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6798072&dopt=Abstract
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New indium-111 labeled biotin derivatives for improved immunotargeting. Author(s): Virzi F, Fritz B, Rusckowski M, Gionet M, Misra H, Hnatowich DJ. Source: Int J Rad Appl Instrum B. 1991; 18(7): 719-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1787080&dopt=Abstract
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Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation. Author(s): Kimura M, Fukui T, Tagami Y, Fujiwaki T, Yokoyama M, Ishioka C, Kumasaka K, Terada N, Yamaguchi S. Source: Journal of Inherited Metabolic Disease. 2003; 26(7): 715-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707523&dopt=Abstract
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Oral glucose tolerance test after high-dose i.v. biotin administration in normoglucemic hemodialysis patients. Author(s): Koutsikos D, Fourtounas C, Kapetanaki A, Agroyannis B, Tzanatos H, Rammos G, Kopelias I, Bosiolis B, Bovoleti O, Darema M, Sallum G. Source: Renal Failure. 1996 January; 18(1): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8820510&dopt=Abstract
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Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer. Author(s): Guy M, Pons L, Namour F, de Nonancourt M, Michalski JC, Hatier R, Gueant JL. Source: Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2001; 11(5): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684816&dopt=Abstract
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Pharmacological biotin supplementation maintains biotin status and function in rats administered dietary carbamazepine. Author(s): Rathman SC, Gregory JF 3rd, McMahon RJ.
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Preliminary X-ray crystallographic analysis of biotin carboxylase isolated from Escherichia coli. Author(s): Waldrop G, Holden HM, Rayment I. Source: Journal of Molecular Biology. 1994 January 7; 235(1): 367-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7904651&dopt=Abstract
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Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study. Author(s): Grana C, Chinol M, Robertson C, Mazzetta C, Bartolomei M, De Cicco C, Fiorenza M, Gatti M, Caliceti P, Paganelli G. Source: British Journal of Cancer. 2002 January 21; 86(2): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870507&dopt=Abstract
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Pretargeting of bacterial endocarditis in rats with streptavidin and 111In-labeled biotin. Author(s): Fogarasi M, Pullman J, Winnard P Jr, Hnatowich DJ, Rusckowski M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1999 March; 40(3): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086715&dopt=Abstract
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Purification and properties of the chloroplastic form of biotin holocarboxylase synthetase from Arabidopsis thaliana overexpressed in Escherichia coli. Author(s): Tissot G, Pepin R, Job D, Douce R, Alban C. Source: European Journal of Biochemistry / Febs. 1998 December 1; 258(2): 586-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874227&dopt=Abstract
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Purification and properties of the synthetase catalyzing the biotination of the aposubunit of transcarboxylase from Propionibacterium shermanii. Author(s): Shenoy BC, Wood HG. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1988 May; 2(8): 2396-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3360240&dopt=Abstract
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Rapid colchicine competition-binding scintillation proximity assay using biotinlabeled tubulin. Author(s): Tahir SK, Kovar P, Rosenberg SH, Ng SC. Source: Biotechniques. 2000 July; 29(1): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907090&dopt=Abstract
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Rapid purification of a functionally active plant sucrose carrier from transgenic yeast using a bacterial biotin acceptor domain. Author(s): Stolz J, Darnhofer-Demar B, Sauer N. Source: Febs Letters. 1995 December 18; 377(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8543043&dopt=Abstract
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Regulation of intestinal biotin transport in the rat: effect of biotin deficiency and supplementation. Author(s): Said HM, Mock DM, Collins JC. Source: The American Journal of Physiology. 1989 February; 256(2 Pt 1): G306-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2919673&dopt=Abstract
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Scintillation proximity assay for human DNA topoisomerase I using recombinant biotinyl-fusion protein produced in baculovirus-infected insect cells. Author(s): Lerner CG, Saiki AY. Source: Analytical Biochemistry. 1996 September 5; 240(2): 185-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8811905&dopt=Abstract
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Serum concentrations of bisnorbiotin and biotin sulfoxide increase during both acute and chronic biotin supplementation. Author(s): Mock DM, Mock NI. Source: The Journal of Laboratory and Clinical Medicine. 1997 March; 129(3): 384-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9042824&dopt=Abstract
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Silver electrodeposition catalyzed by colloidal gold on carbon paste electrode: application to biotin-streptavidin interaction monitoring. Author(s): Gonzalez-Garcia MB, Costa-Garcia A. Source: Biosensors & Bioelectronics. 2000; 15(11-12): 663-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213227&dopt=Abstract
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Simple purification of highly active biotinylated P-glycoprotein: enantiomer-specific modulation of drug-stimulated ATPase activity. Author(s): Julien M, Kajiji S, Kaback RH, Gros P. Source: Biochemistry. 2000 January 11; 39(1): 75-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10625481&dopt=Abstract
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Supplemental biotin for swine. II. Influence of supplementation to corn- and wheatbased diets on reproductive performance and various biochemical criteria of sows during four parities. Author(s): Bryant KL, Kornegay ET, Knight JW, Webb KE Jr, Notter DR. Source: Journal of Animal Science. 1985 January; 60(1): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3972736&dopt=Abstract
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Supplemental biotin for swine. III. Influence of supplementation to corn- and wheatbased diets on the incidence and severity of toe lesions, hair and skin characteristics and structural soundness of sows housed in confinement during four parities. Author(s): Bryant KL, Kornegay ET, Knight JW, Veit HP, Notter DR. Source: Journal of Animal Science. 1985 January; 60(1): 154-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3972737&dopt=Abstract
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The application of a biotin-anti-biotin gold technique providing a significant signal intensification in electron microscopic immunocytochemistry: a comparison with the ultrasmall immunogold silver staining procedure. Author(s): Muller-Hocker J, Schafer S, Sendelhofert A, Weis S. Source: Histochemistry and Cell Biology. 1998 February; 109(2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9504772&dopt=Abstract
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The clinical spectrum of biotin-treatable encephalopathies in Saudi Arabia. Author(s): Dabbagh O, Brismar J, Gascon GG, Ozand PT. Source: Brain & Development. 1994 November; 16 Suppl: 72-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726384&dopt=Abstract
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The effect of biotin supplementation on ascorbic acid metabolism in chickens. Author(s): Lechowski J, Nagorna-Stasiak B. Source: Arch Vet Pol. 1993; 33(1-2): 19-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8055051&dopt=Abstract
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The effects of dietary biotin supplementation on vertical fissures of the claw wall in beef cattle. Author(s): Campbell JR, Greenough PR, Petrie L. Source: Can Vet J. 2000 September; 41(9): 690-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992986&dopt=Abstract
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The enzymatic synthesis of holotranscarboxylase from apotranscarboxylase and (+)biotin. ii. investigation of the reaction mechanism. Author(s): LANE MD, ROMINGER KL, YOUNG DL, LYNEN F. Source: The Journal of Biological Chemistry. 1964 September; 239: 2865-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14216437&dopt=Abstract
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The enzymatic synthesis of holotranscarboxylase from apotranscarboxylase and (+)biotin. i. purification of the apoenzyme and synthetase; characteristics of the reaction. Author(s): LANE MD, YOUNG DL, LYNEN F. Source: The Journal of Biological Chemistry. 1964 September; 239: 2858-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14216436&dopt=Abstract
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The impact of parity and duration of biotin supplementation on white line disease lameness in dairy cattle. Author(s): Potzsch CJ, Hedges VJ, Blowey RW, Packington AJ, Green LE. Source: Journal of Dairy Science. 2003 August; 86(8): 2577-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939081&dopt=Abstract
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The influence of long-term supplementation with biotin on the prevention of lameness in pasture fed dairy cows. Author(s): Fitzgerald T, Norton BW, Elliott R, Podlich H, Svendsen OL. Source: Journal of Dairy Science. 2000 February; 83(2): 338-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714870&dopt=Abstract
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The long-term influence of biotin supplementation on hoof horn quality in horses. Author(s): Geyer H, Schulze J. Source: Schweiz Arch Tierheilkd. 1994; 136(4): 137-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8202678&dopt=Abstract
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The regulation of glycan processing in glycoproteins. The effect of avidin on individual steps in the processing of biotinylated glycan derivatives. Author(s): Shao MC, Chin CC, Caprioli RM, Wold F. Source: The Journal of Biological Chemistry. 1987 March 5; 262(7): 2973-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2950092&dopt=Abstract
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Trifunctional conjugation reagents. Reagents that contain a biotin and a radiometal chelation moiety for application to extracorporeal affinity adsorption of radiolabeled antibodies. Author(s): Wilbur DS, Chyan MK, Hamlin DK, Kegley BB, Nilsson R, Sandberg BE, Brechbiel M. Source: Bioconjugate Chemistry. 2002 September-October; 13(5): 1079-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236790&dopt=Abstract
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Urinary biotin analogs increase in humans during chronic supplementation: the analogs are biotin metabolites. Author(s): Mock DM, Heird GM. Source: The American Journal of Physiology. 1997 January; 272(1 Pt 1): E83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9038855&dopt=Abstract
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Visualization of the chicken oocyte lipoprotein receptor by ligand blotting with biotinylated plasma and yolk very low density lipoproteins. Author(s): Elkin RG, Schneider WJ. Source: Poultry Science. 1994 July; 73(7): 1127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7937474&dopt=Abstract
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to biotin; 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 Alopecia Source: Integrative Medicine Communications; www.drkoop.com Brittle Nails Source: Healthnotes, Inc.; www.healthnotes.com Candidiasis Source: Integrative Medicine Communications; www.drkoop.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com
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Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Hair Disorders Source: Integrative Medicine Communications; www.drkoop.com Hair Loss Source: Integrative Medicine Communications; www.drkoop.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com Infection Source: Integrative Medicine Communications; www.drkoop.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Phenylketonuria Source: Healthnotes, Inc.; www.healthnotes.com Seborrheic Dermatitis Source: Healthnotes, Inc.; www.healthnotes.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Skin Conditions Source: Integrative Medicine Communications; www.drkoop.com Weight Loss Source: Integrative Medicine Communications; www.drkoop.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com Yeast Infection Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com
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Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Carbamazepine Alternative names: Atretol, Carbatrol, Epitol, Tegretol, Tegretol XR Source: Prima Communications, Inc.www.personalhealthzone.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glyburide Source: Healthnotes, Inc.; www.healthnotes.com Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Insulin Source: Healthnotes, Inc.; www.healthnotes.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Macrolides Source: Integrative Medicine Communications; www.drkoop.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Phenobarbital Source: Healthnotes, Inc.; www.healthnotes.com Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com
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Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Topical Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON BIOTIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to biotin. 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 “biotin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on biotin, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Biotin 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 biotin. 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: •
Effects of Dietary Biotin on Liver Pyruvate Carboxylase and Metabolism of Poultry by Atwal, Avtar Singh; AdvDeg from University of Alberta (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04917
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Genetic and Biochemical Characterization of Biotin-Responsive Multiple Carboxylase Deficiency by Saunders, Mary E; PhD from University of Toronto (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK58247
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Metabolic Alterations of Free and Protein-Bound Biotin in Rats during Dietary Biotin Manipulation and Endotoxin Exposure by Lewis, Brandon James, PhD from University of Florida, 2003, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3095102
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Regulation of Acetyl-CoA Carboxylase and Role of Biotin in Cellular Functions by Bhullar, Rajinder P; PhD from The University of Manitoba (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK62446
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Regulation of Expression of Biotin Genes in Escherichia coli K-12 by Nath, Swapan Kumar; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31446
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Studies of the Metabolic Role of Biotin: an Examination of the Biotin Deficiency Syndrome with Particular Emphasis on the Involvement of Biotin in Protein Biosynthesis in the Rat by Boeckx, Roger Louis O; PhD from The University of Manitoba (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK16883
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Studies on N-Carboxy and N-Phosphono Ureas and Methyl Ethylene Phosphate Mechanisms of Biotin Mediated Carboxyl Transfer; Mechanisms of Nucleophilic Substitution at Phosphorus and Reactivity of Five Membered Phosphorus Containing Rings by Thatcher, Gregory Robert James; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29369
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Supplemental Biotin Effects on Performance and Dynamics of Fat Mobilization and on in Vitro Fiber Digestion Using Periparturient Holstein Cows by Rosendo, Oswaldo, PhD from University of Florida, 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3096665
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The Biotin Requirement of Cells in Culture and the Uptake of the Avidin-Biotin Complex by Chalifour, Lorraine Elizabeth; PhD from The University of Manitoba (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK54266
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. PATENTS ON BIOTIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “biotin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on biotin, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Biotin By performing a patent search focusing on biotin, 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
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on biotin: •
Active ingredient combinations or adducts of biotin and/or biotin derivatives and cyclodextrins and use of such active ingredient combinations in cosmetic preparations Inventor(s): Max; Heiner (Hamburg, DE), Raschke; Thomas (Pinneberg, DE) Assignee(s): Beiersdorf AG (Hamburg, De) Patent Number: 6,436,414 Date filed: August 21, 2000 Abstract: Active ingredient combinations of cyclodextrins and biotin and/or one or more biotin derivatives for use in cosmetic or dermatological formulations. Excerpt(s): The present invention relates to cosmetic or dermatological preparations comprising active ingredients for the care and protection of the skin, in particular sensitive skin and dry skin and, very particularly, skin ageing or aged by intrinsic and/or extrinsic factors, and for assisting the skin's own lipid metabolism, and to the use of such active ingredients and combinations of such active ingredients in the field of cosmetic and dermatological skincare. The term "cosmetic skincare" primarily means the strengthening or rebuilding of the skin's natural function as a barrier against environmental influences (e.g. dirt, chemicals, microorganisms) and against the loss of endogenous substances (e.g. water, natural fats, electrolytes). Impairment of this function may lead to increased resorption of toxic or allergenic substances or attack by microorganisms, leading to toxic or allergic skin reactions. Web site: http://www.delphion.com/details?pn=US06436414__
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Arrays with modified oligonucleotide and polynucleotide compositions Inventor(s): Dale; Roderic M. K. (Wilsonville, OR) Assignee(s): Oligos Etc. Inc. (wilsonville, Or) Patent Number: 6,440,723 Date filed: March 17, 2000 Abstract: Binding units such as avidin or biotin are placed on tightly defined areas of a solid planar support surface. Polymer sequences such as oligonucleotides are synthesized with a complementary binding unit attached, preferably via a linker moiety. The polymer/linker/binding units are then placed on the binding units on the support surface and an array is formed. Excerpt(s): The field of this invention is arrays having associated oligonucleotides and/or polynucleotides, methods of producing such arrays, and uses thereof. Arrays of binding agents, such as oligonucleotides and polynucleotides, have become an increasingly important tool in the biotechnology industry and related fields. These arrays, in which a plurality of binding agents are deposited onto a solid support surface in the form of an array or pattern, find use in a variety of applications, including drug screening, nucleic acid sequencing, mutation analysis, and the like. One important use of arrays is in the analysis of differential gene expression, where the expression of genes in different cells, normally a cell of interest and a control, is compared and any
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discrepancies in expression are identified. In such assays, the presence of discrepancies indicates a difference in the classes of genes expressed in the cells being compared. In methods of differential gene expression, arrays find use by serving as a substrate with associated binding fragments such as oligonucleotides. Nucleic acid sequences are obtained from analogous cells, tissues or organs of a healthy and diseased organism, and hybridized to the immobilized set of binding fragments associated with the array. Differences between the resultant hybridization patterns are then detected and related to differences in gene expression in the two sources. Web site: http://www.delphion.com/details?pn=US06440723__ •
Biosensor with modified precious metal surface and process for the preparation thereof Inventor(s): Nicolaus; Thomas (Munchen, DE), Wischerhoff; Erik (Munchen, DE) Assignee(s): Schleicher; Franz (ingolstadt, De) Patent Number: 6,472,224 Date filed: April 15, 1999 Abstract: The present invention relates to a biosensor (affinity sensor) in which a hydrogel, a surfactant layer or biotin are bonded to the biosensor's precious metal surface by means of a short-chained linker, as well as to the process for the preparation thereof. A complete covering of the biosensor surface with the hydrogel, the surfactant layer or the biotin is achieved by hydrogen bonds, aromatic-aromatic interactions or by covalent bonds. Excerpt(s): This application claims priority to German Patent Application Nos. 198 17 180.3-52 (filed Apr. 17, 1998 and issued Apr. 27, 2000 as German Patent No. DE 198 17 180) and 198 53 428.0 (filed Nov. 19, 1998), which are hereby incorporated herein by reference in their entirety. This invention relates to a biosensor (affinity sensor) in which a hydrogel, a surfactant layer or biotin is bonded to the sensor's precious metal surface by a short chain linker, and further relates to the procedure for the preparation thereof. For signal generation, the surfaces of surface plasmon resonance (SPR) based affinity sensors must possess a precious metal layer, usually of gold, with a thickness of approx. 50 nm. However, direct bonding of receptors, typically proteins, to the precious metal surface has proven to be impractical because the receptors are easily denatured in this environment and as a result lose their receptor function. Also, bare sections of the precious metal surface can be subject to unspecific adsorption phenomena which seriously flaw the measurement results. Web site: http://www.delphion.com/details?pn=US06472224__
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Biotin biosynthetic genes Inventor(s): Furuichi; Yasuhiro (Kamakura, JP), Hoshino; Tatsuo (Kamakura, JP), Kimura; Hitoshi (Odawara, JP), Kiyasu; Tatsuya (Fujisawa, JP), Nagahashi; Yoshie (Fujisawa, JP) Assignee(s): Roche Vitamins, Inc. (parsipanny, Nj) Patent Number: 6,365,388 Date filed: June 14, 2000
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Abstract: The present invention relates to the production process of biotin by fermentation using a genetically engineered microorganism, and DNA sequences and vectors to be used in such process. Excerpt(s): The present invention relates to the production process of biotin by fermentation using a genetically engineered organism. Biotin is one of the essential vitamins for nutrition of animals, plants, and microorganisms, and very important as medicine or food additives. Biotin biosynthesis of Escherichia coli has been studied well, and it has been clarified that biotin is synthesized from pimelyl CoA via 7 keto-8-amino pelargonic acid (KAPA), 7,8-diamino pelargonic acid (DAPA) and desthiobiotin (DTB) [Escherichia coli and Salmonella typhimurium, Cellular and Molecular Biology, 544, (1987)]. The analysis of genetic information involved in the biosynthesis of biotin has been advanced on Escherichia coli [J. Biol. Chem., 263, 19577, (1988)] and Bacillus sphaericus (U.S. Pat. No. 5,096,823). At least four enzymes are known to be involved in this biosynthetic pathway. These four enzymes are encoded by the bioA, bioB, bioD and bioF genes. The bioF gene codes for KAPA synthetase which catalyzes the conversion of pimelyl CoA to KAPA. The bioA gene codes for DAPA aminotransferase which converts KAPA to DAPA. The bioD gene codes for DTB synthetase which converts DAPA to DTB. The bioB gene codes for biotin synthase which converts DTB to biotin. It has been also reported that the bioC and bioH genes are involved in the synthesis of pimelyl CoA in Escherichia coli. Web site: http://www.delphion.com/details?pn=US06365388__ •
Chimeric biotin-binding papillomavirus protein Inventor(s): Kast; W. Martin (Willowbrook, IL), Mueller; Martin (Heidelberg, DE), Nieland; John D. (Martinsried, DE), Velders; Markwin P. (Forest Park, IL) Assignee(s): Loyola University of Chicago (maywood, Il) Patent Number: 6,380,364 Date filed: October 6, 1999 Abstract: The present invention provides a chimeric protein including a first domain which includes at least a portion of a papillomavirus L1 or L2 protein and a second domain which includes a biotin-binding polypeptide. The invention also provides papillomaviruses, capsomeres, and VLPs including such chimeric proteins and a method for delivering biotinylated substances to cells using such reagents. Excerpt(s): This invention relates to a chimeric biotin-binding papillomavirus protein. Papillomavirus are causative agents for several types of epithelial and mucosal diseases. Of particular concern is that certain strains of papillomavirus are associated with genital cancers, cancers of the head and neck, and also rectal cancers (see, e.g., Iwasawa et al., J. Urol., 149, 59-63 (1993); Koutsky et al., N. Engl. J. Med., 327, 1272-78 (1992)). Considerable efforts, therefore, are underway to prevent the spread of this virus by developing a prophylactic vaccine and novel treatments for papillomavirus-induced lesions (see, e.g., Cason et al., Vaccine, 11, 603-11 (1993); Crawford, Cancer Suev., 16, 215-29 (1993), Schiller et al., in Papillomavirus-Like Particles: Basic and Applied Studies (Lacey, C., ed., 101-12 (Leeds Medical Information, Leeds, U.K., 1996)). Papillomaviruses are nonenveloped double-stranded DNA viruses about 55 nm in diameter with an approximately 8-kb genome in a nucleohistone core (Baker et al., Biophys J. 60, 1445-56 (1991)). The capsids include two viral proteins (L1 and L2) of about 55 kDa and 75 kDa, respectively (Larson et al., J. Virol., 61, 3596-3601 (1987)). L1 is the major capsid protein,
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and it is arranged in 72 pentameres within the capsid. In fact, L1 has the ability to selfassemble into virus-like particles (VLPs) upon production of the L1 protein in eukaryotic cells (see, e.g., Hagensee et al., J. Virol., 67, 315-22 (1993); Kirnbauer et al., J. Virol., 67, 6929-36 (1993)). The function and position of L2 within the virion are not clear, although the protein is assembled with L1 into VLPs when coexpressed in cells. The ratio of L1 to L2 within VLPs is about 30:1 (Kirnbauer et al., J. Virol., 67, 6929-36 (1993)). Web site: http://www.delphion.com/details?pn=US06380364__ •
Circularly permuted biotin binding proteins Inventor(s): Stayton; Patrick S. (Seattle, WA) Assignee(s): University of Washington (seattle, Wa) Patent Number: 6,492,492 Date filed: April 2, 1999 Abstract: Circularly permuted proteins are described wherein the natural termini of the polypeptide are joined and the resulting circular protein is opened at another point to create new C- and N- termini. The resulting protein exhibits some altered characteristic such as reduced substrate binding, for example. Fusion proteins can be made from the circularly permuted protein by attaching the second polypeptide to these newly created termini. These fusion proteins will have altered properties from a fusion protein made by attaching the second polypeptide to the natural termini. For example, the second peptide or protein can be attached at a position where it is more accessible to its substrate or intended target. In the preferred embodiment, the base circularly permuted biotin binding protein. In one embodiment, a flexible polypeptide loop important for the binding of biotin was opened by creation of the circularly permuted protein. The original termini (residues 13 and 139 of SEQ ID NO:1) were joined by a linker. The biotin association constant was reduced approximately six orders of magnitude below that of wild type streptavidin to 10.sup.7 M.sup.-1. Fusion proteins of the circularly permuted streptavidin can be made with secondary peptides/proteins such as IgG binding protein A or single-chain antibodies. Excerpt(s): The present invention is in the field of modified streptavidin, and more particularly in the area of streptavidin fusion proteins wherein the base polypeptide is streptavidin having a circularly permuted loop. Fusion proteins are polypeptide chains consisting of two or more polypeptides fused together into a single polypeptide chain. Streptavidin fusion proteins have been reported, for example, that combine the biotin binding capabilities of streptavidin with that of a second protein, such as IgG-binding protein A (Sano and Cantor, Bio/Technology 9:1377-1381 (1992), and U.S. Pat. No. 5,328,985 to Sano et al.), metallothionein (Sano, et al., P. N. A. S. USA 89:1534-1538 (1992)), single chain antibodies (Dubel et al., J. Immul. Methods. 178:201-209 (1995)) and the human low density lipoprotein (LDL) receptor (U.S. Pat. No. 4,839,293 to Cantor et al.). These proteins include wild-type streptavidin attached to the second protein. Tight binding of biotin to the streptavidin is substantially maintained. The high affinity of streptavidin for biotin, with a K.sub.a of approximately 2.5.times.10.sup.13 M.sup.-1, has been advantageously utilized in many existing diagnostic and separation technologies, and in targeted drug/imaging agent delivery systems. However, the extremely high affinity of streptavidin for biotin can be detrimental in applications where reversible immobilization of streptavidin or biotinylated targets is ultimately desirable. An important example is affinity separations, where a biotinylated target molecule is captured with streptavidin and where subsequent release and recycling of
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the biotinylated target or capture agent (e.g. antibody) is desired. Similarly, in drug delivery applications where the streptavidin-biotin system forms the targeting and/or delivery component, the exceptionally slow biotin dissociation kinetics limits potential applications utilizing diffusion of the biotinylated imaging agent or drug to the therapeutic target, and may also result in slow in vivo clearance of biotinylated imaging agents. Web site: http://www.delphion.com/details?pn=US06492492__ •
Complex of biotinylated viral vector and ligand for targeted gene delivery Inventor(s): Keller; Jonathan R. (Frederick, MD), Smith; Jeffrey S. (Bethesda, MD), Spence; Sally E. (Frederick, MD) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,555,367 Date filed: June 15, 2000 Abstract: The present invention provides a composition for targeted delivery of a nucleic acid to a cell comprising a biotinylated recombinant adenovirus, wherein biotin is covalently linked to the recombinant adenovirus, wherein the recombinant adenovirus comprises the nucleic acid, and wherein the recombinant adenovirus is linked via streptavidin to a biotinylated targeting moiety. Also provided by this invention is a method for targeted delivery of a nucleic acid to a selected cell in a subject comprising administering to the subject a composition comprising a biotinylated recombinant adenovirus, wherein biotin is covalently linked to the recombinant adenovirus, wherein the recombinant adenovirus comprises the nucleic acid, and wherein the recombinant virus is linked via streptavidin to a biotinylated targeting moiety that specifically targets the selected cell. Excerpt(s): The present invention is in the field of targeted gene delivery. Specifically, the invention relates to recombinant viral vectors for targeted delivery to selected cells, wherein the recombinant virus is a small, encapsidated virus, such as adenovirus or adeno-associated virus. Recent attempts to target gene transfer to human cells have focused on the use of retroviral and adenoviral vectors. However, the most promising current vectors have resulted in limited success, due in part to the inability to target specific cell types such as hematopoietic stem cells, and the need to culture target cells in vitro to promote cell cycling which can result in the loss of stem cell function. The ability to target gene transfer to specific cell types in situ would greatly enhance current approaches to gene therapy. Several approaches have been taken to target viral and non viral vectors that include using ligands, antibodies or peptides in the vector construction thereby redirecting virus infection through antigens or receptors expressed on specific cell types. Early experiments designed to redirect the host range of retroviruses by molecular modification of ecotropic envelopes to recognize cellular receptors through antigen binding, ligand or peptide sequences were unsuccessful. It has subsequently been shown that efficient uncoating of the virus requires a conformational change in a subunit of the envelope protein which is only induced upon interaction of the retrovirus particle with its cognate receptor; thus retroviruses directed to alternate receptors do not yield high frequencies of infection. Web site: http://www.delphion.com/details?pn=US06555367__
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Composition and method for modulating nutrient partitioning Inventor(s): McCleary; Larry (1795 Foothills Dr. South, Golden, CO 80401) Assignee(s): None Reported Patent Number: 6,579,866 Date filed: December 28, 2000 Abstract: A nutritional supplement composition for modulating nutrient partitioning in a human so as to increase oxidation of fat and promote increased storage of glycogen is composed of hydroxycitric acid, carnitine, biotin, a gluconeogenic substrate, and, optionally, one or more of chromium, conjugated linoleic acid, coenzyme Q10, eicosapentaenoic acid, pyridoxine, alpha-lipoic acid, magnesium, and gymnema sylvestre. A method for modulating nutrient partitioning in a human involves orally or parenterally administering the aforementioned composition to the human, preferably on a daily basis, for a therapeutically effective period of time. Preferably, the method further involves having the human follow a specific dietary regimen wherein the glycemic index is less than 60 and the daily calorie consumption from carbohydrates is less than about 50% and the daily calorie consumption from protein is at least about 20%. Optionally, the method further involves an exercise program, a stress reduction program and/or a blood donation program. Excerpt(s): This invention relates to compositions and methods for modulating nutrient partitioning. More particularly, the present invention provides a composition and a method for modulating nutrient partitioning in humans so as to normalize nutrient pathways which play a key role in numerous metabolic disorders, the composition and method being designed to prevent, delay or reverse such disorders. Disorders of nutrient partitioning leading to biochemical signaling abnormalities form the basis for a group of metabolic disorders. These include but are not limited to insulin resistance, hyperinsulinemia, Syndrome X, hypertriglyceridemia and/or low HDL syndrome, high RQ (respiratory quotient) syndrome, obesity, chronic fatigue syndrome, small dense LDL syndrome, recidivism from weight loss, glucolipoxia, premature aging, memory loss, endothelial dysfunction, vascular disease, hypertension, postprandial hyperlipidemia, certain types of cancer, metabolic inflexibility and others. The basic abnormality is similar in each circumstance but manifests clinically in different ways depending upon the organ involved, the individual's genetic makeup, age, sex and other factors. The two major macronutrient fuels are fat and carbohydrate (which is stored in the body as glycogen). In the body, fat and carbohydrate are combined in certain proportions to generate the fuel mix the body burns at any point in time. If the fuel mix contains more carbohydrate, it contains relatively less fat and vice versa. Because there is minimal metabolic transformation between carbohydrate and fat, if more fat is being burned, then less is being stored and vice versa. The same holds true for carbohydrate, i.e., if more carbohydrate is being burned, then less is being stored and vice versa. Web site: http://www.delphion.com/details?pn=US06579866__
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Cyclodextrin dimers with spacers having peptide structures for encapsulation of pharmaceutically active substances with potential high side-effects Inventor(s): Hoffmann; Ralph (Erkrath, DE), Moser; Jorg G. (Duesseldorf, DE) Assignee(s): Ceramoptec Industries, Inc. (east Longmeadow, Ma) Patent Number: 6,602,988 Date filed: January 12, 2001 Abstract: A rigidly spaced, cyclodextrin dimers having a preselected breaking point within the spacer sequence so as to controllably release the active pharmaceutically active substance only after it reaches the desired treatment site is described. These preselected breaking points are stable in blood but are cleavable within cells. In preferred embodiments, the cyclodextrin-pharmaceutically active substance complex is targeted to specific sites via incorporation of specific antibodies for the targeted sites, typically by complexing a biotin-avidin system to specific antibodies which thereby targets the complex to a specific site. Once at the site as the complex is taken up into the cell the preselected break point is cleaved and the encapsulated pharmaceutically active substance becomes available for action within the targeted cell. This approach permits the use of highly effective and efficient pharmaceutically active substances, whose safety restricts use to last chance efforts or which are unable to qualify for human use due to their potential side effects. In a preferred embodiment peptide structures are used as part of the spacers between bridged cyclodextrins The cyclodextrin oligomers are complexed with pharmaceuticals with potential high side effects to safely, efficiently achieve the therapeutic action dsired. Excerpt(s): The present invention relates to therapies with pharmaceutically active substances with potentially high side-effects, which have to be transported in the blood and delivered to specific target cells without influencing healthy organs. Therapies with very effective pharmaceutically active substances e.g. with antimitotic properties for cancer therapy often suffer from the fact that healthy organs are damaged severely by the therapy. These side effects often make the use of certain therapies impossible even if the therapy would be effective in curing the diseased organ. Therefore it is desirable to achieve specific targeting of the pharmaceutically active substances to the diseased organ or cells, and moreover to inhibit the delivery of the pharmaceutically active substance to healthy organs. Often a localized application of the pharmaceutically active substance to the diseased site is not possible, but the pharmaceutically active substance has to be administered systemically through the blood stream and is accessible for the whole organism. One way to prevent this is to build complexes with carrier molecules that mediate an inert transport through the blood and selectively release the pharmaceutically active substance at the target site. In patent description in Pat. Ser. No. 09/554,223 by Jorg G. Moser (published as WO 9924474) a method was introduced to detoxify pharmaceuticals with dangerous side effects by physical encapsulation into cyclodextrin [CD] oligomers with a relatively rigid spacer structure B. Web site: http://www.delphion.com/details?pn=US06602988__
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Derivatized biotin compounds and methods of use Inventor(s): Amspacher; David R. (Baton Rouge, LA), Saraiva; Marcelo C. (San Antonio, TX), Strongin; Robert M. (Baton Rouge, LA), Waldrop; Grover L. (Baton Rouge, LA) Assignee(s): Board of Supervisors of Louisiana State University and Agricultural and (baton Rouge, La) Patent Number: 6,555,528 Date filed: April 6, 2001 Abstract: An efficient synthesis for the selective and efficient 1'-N derivatization of biotin is reported. The derivatized biotin acts as a stable analog of the carboxyphosphate intermediate in naturally-occurring biotin-mediated CO.sub.2 transfer. The synthesis may readily be scaled up to perform large-scale, selective acylations of biotin. The stable analog of the intermediate can inhibit the activity of the biotin carboxylase enzymes such as acetyl CoA carboxylase, and HIV protease. The functionalization at the 1'-N of biotin results in the attachment of an electrophilic "handle" amenable to reaction with a wide variety of nucleophiles to generate a new family of biotin analogs. Excerpt(s): This invention pertains to derivatized biotin compounds, and to methods of using those compounds. R. Guchhait et al., J. Biol. Chem. vol. 249, pp. 6646-6656 (1974) showed that in the first partial reaction shown above, biotin is carboxylated on the 1'-N. Since bicarbonate is the source of CO.sub.2 for all biotin-dependent carboxylases, carboxylation of the 1'-N of biotin is accomplished by activating bicarbonate through phosphorylation with ATP to form a carboxyphosphate intermediate. The carboxyl group is then transferred from the carboxyphosphate intermediate to biotin to form carboxybiotin. In the field of biotechnology, biotin has become an important reagent in methods to label, detect, and purify proteins and nucleic acids. These methods are based on the remarkable affinity between biotin and the proteins avidin and streptavidin. The dissociation constant of biotin from avidin or streptavidin is about 10.sup.-15 M, one of the strongest known interactions between a protein and a ligand. While all parts of the biotin molecule contribute to this tight binding, hydrogen bonding donation by the ureido nitrogens is the major contributor. Web site: http://www.delphion.com/details?pn=US06555528__
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Dietary supplement composition and method for improving and maintaining healthy skin Inventor(s): Alioto; Samuel J. (Saint Louis, MO), Popp; Karl F. (Schodack Landing, NY) Assignee(s): Stiefel Laboratories, Inc. (oak Hill, Ny) Patent Number: 6,630,158 Date filed: October 30, 2001 Abstract: A dietary supplement composition for promoting healthy skin comprised of lycopene and other carotenoids, selenium, chromium and biotin. Excerpt(s): This invention relates to dietary supplement compositions useful for improving or maintaining the skin. This invention relates to new and improved dietary supplement compositions for and methods of promoting healthy skin in humans and other animals. More particularly it relates to a composition comprised of lycopene, biotin, selenium, chromium and carotenoids and the administration of such a
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composition to human or animal subjects. More particularly, the invention relates to various compositions of dietary supplements designed to promote optimal levels of such nutrients in the body and methods of using such compositions. Web site: http://www.delphion.com/details?pn=US06630158__ •
DNA attachment to support structures Inventor(s): Balhorn; Rodney L. (Livermore, CA), Barry; Christopher H. (Fresno, CA) Assignee(s): The Regents of the University of California (oakland, Ca) Patent Number: 6,420,112 Date filed: July 21, 1999 Abstract: Microscopic beads or other structures are attached to nucleic acids (DNA) using a terminal transferase. The transferase adds labeled dideoxy nucleotide bases to the ends of linear strands of DNA. The labels, such as the antigens digoxigenin and biotin, bind to the antibody compounds or other appropriate complementary ligands, which are bound to the microscopic beads or other support structures. The method does not require the synthesis of a synthetic oligonucleotide probe. The method can be used to tag or label DNA even when the DNA has an unknown sequence, has blunt ends, or is a very large fragment (e.g., >500 kilobase pairs). Excerpt(s): This invention relates to a method for attaching nucleic acids, such as DNA, to microscopic beads or other support structures using a terminal transferase. Recent technical advancements in nanomanipulation have allowed the mechanical behavior of single DNA molecules to be studied. These techniques include the use of microspheres, magnetic beads, microfibers, microneedles, optical traps, and hydrodynamic flow. The attachment of microspheres to DNA has proven useful to manipulate DNA for placement or immobilization on a selected substrate or mechanical support, where the DNA strand can be confined in an extended conformation. Once the DNA is affixed to a substrate, a variety of processes (e.g., laser tweezers, scanning probe microscopy) can be used to sequence or map gene locations of the DNA. In addition, tethering microspheres to DNA may be useful in purification or separation methods that selectively isolate labeled or tagged DNA fragments. Conventional techniques of tethering or attaching DNA to microspheres rely on hybridization and ligation of manufactured, labeled single-stranded DNA probes to known DNA sequences. U.S. Pat. No. 5,674,743 to Ulmer discusses methods in the art for attaching the DNA to a microscopic bead and is incorporated herein by reference. One method is to first couple specific oligonucleotide linkers to the bead using known techniques, and then to use DNA ligase to link the DNA to the linker on the bead. Oligonucleotide linkers can be employed which specifically hybridize to unique sequences at the end of the DNA fragment, such as the overlapping end from a restriction enzyme site or the "sticky ends" of bacteriophage lambda based cloning vectors. Web site: http://www.delphion.com/details?pn=US06420112__
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DNA fragments containing biotin biosynthetase gene and use of the same Inventor(s): Akimaru; Jiro (Nishinomiya, JP), Mitsuda; Satoshi (Takarazuka, JP), Mukumoto; Fujio (Toyonaka, JP), Nishio; Shoichi (Toyonaka, JP) Assignee(s): Sumitomo Chemical Company, Limited (osaka, Jp) Patent Number: 6,410,293 Date filed: December 3, 1998 Abstract: A DNA fragment containing a gene concerned in biotin biosynthesis and derived from a microorganism belonging to the genus Sphingomonas, a plasmid containing said DNA fragment, and a biotin-producing transformant containing said plasmid. There is provided a technique for utilizing a gene concerned in biotin biosynthesis and derived from a microorganism belonging to the genus Sphingomonas, for breeding of a biotin-producing micro-organism by genetic engineering. Excerpt(s): This application is the national phase under 35 U.S.C.sctn.371 of prior PCT International Application No. PCT/JP98/00858 which has an International filing date of Mar. 2, 1998 which designated the United States of America, the entire contents of which are hereby incorporated by reference. The present invention relates to a DNA fragment containing at least one gene concerned in biotin biosynthesis and utilization thereof. Biotin is an essential vitamin for human beings, animals, plants and some microorganisms and is useful as a food additive for human beings or animals. As a process for producing biotin by using a microorganism, there have been known a process using a streptomyces or a micro-monospore (JP-B-41-21756), a process using a sporobolomyces (JP-B-42-3074), a process using a bacillus, a chromo-bacterium or a pseudomonas (JP-A-56-160998), a process using a sphingomonas (JP-A-6-133790), etc. There have been also proposed processes for breeding a microorganism in which a gene concerned in biotin biosynthesis and isolated from a microorganism capable of producing biotin is introduced into another microorganism by a genetic engineering technique to promote the expression of the gene concerned in biotin biosynthesis, whereby the activity of an enzyme capable of catalyzing biotin biosynthesis reaction is increased to improve the biotin productivity (JP-A-61-202686, JP-A-2-27980, JP-A-7231789, etc.). Web site: http://www.delphion.com/details?pn=US06410293__
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Fermentation process Inventor(s): Anderson; Kevin W. (Indian Springs, OH), Wenzel; J. Douglas (Cincinnati, OH) Assignee(s): Cognis Corporation (gulph Mills, Pa) Patent Number: 6,569,670 Date filed: January 4, 2001 Abstract: A fermentation medium containing: (a) a source of metabolizable carbon and energy; (b) a source of inorganic nitrogen; (c) a source of phosphate; (d) at least one metal selected from the group consisting of an alkali metal, an alkaline earth metal, a transition metal, and mixtures thereof; and (e) biotin, substantially free of particulate matter and bacteria. A fatty material may be added to an aqueous suspension containing at least one dicarboxylic acid to modify the rheological characteristics of the suspension.
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Excerpt(s): This invention relates to an improved fermentation medium and process for making an aliphatic polycarboxylic acid using said medium. Long-chain alpha, omegadicarboxylic acids, i.e., those having a carbon number of 9 or higher, are used as raw materials in the synthesis of a variety of chemical products and polymers. Diacids with carbon numbers greater than four are currently produced almost exclusively by nonbiological conversion processes. These types of chemical processes for the production of diacids have a number of limitations and disadvantages. Each process is restricted to the production of diacids of specific carbon chain lengths, based on the starting material used. For example, the dodecandioic acid process begins with butadiene, therefore the products of this reaction process are limited to acids with chain lengths in multiples of four. In addition, the processes are based on nonrenewable petrochemical feedstocks, and the multireaction conversion process produces unwanted byproducts which result in yield losses, heavy metal wastes, and nitrogen oxides which must be destroyed in a reduction furnace. Web site: http://www.delphion.com/details?pn=US06569670__ •
Galenic formulation containing biotin Inventor(s): Bunger; Joachim (Gross-Umstadt-Heubach, DE), Driller; Hansjurgen (GrossUmstadt, DE), Huschka; Christoph (Halle, DE), Motitschke; Lothar (Hilden, DE), Neubert; Reinhard (Halle, DE), Wohlrab; Wolfgang (Halle, DE) Assignee(s): Merck Patent Gmbh (darmstadt, De) Patent Number: 6,660,251 Date filed: July 27, 2001 Abstract: The invention relates to galenic formulations which contain a) one or more compounds selected from biotin, its physiologically compatible salts, biotin esters and the steroisomeric forms of these compounds; and b) one or more compounds selected from urea and urea derivatives. The above formulations are suitable for use as topically administered formulations for the cosmetic and/or medical treatment of the skin, hair and/or nails. Excerpt(s): The invention relates to topically applicable galenic formulations which contain one or more compounds selected from biotin, the physiologically tolerable salts of biotin, biotin esters and the stereoisomeric forms of these compounds and one or more compounds selected from urea and urea derivatives and are suitable for the cosmetic or medicinal treatment of skin, hair and/or nails, for example for the treatment of diseases or functional disorders of human or animal skin, hair and/or nails. The efficacy of biotin in skin, hair and nail diseases has been assessed in different ways in the past. Although, by means of continuous biotin therapy, it was possible to show the efficacy in the case of soft, brittle and splitting nails, different forms of alopecia and atopic and seborrheic dermatitis in a detectable manner, use remained sparing, as this is associated, despite no side effects at all, with the necessity of an extended treatment period of several months (R. Bitsch et al. (1994) Biotin, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart; V. E. Colombo et al. (1990) Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. J. Am. Acad. Dermatol. 23: 1127-1132; G. L. Floersheim (1989) Behandlung bruchiger Fingernagel mit Biotin [Treatment of brittle fingernails with biotin]. Z. Hautkr. 64: 41-48; G. L. Floersheim (1992) Prufung der Wirkung von Biotin auf Haarausfall und Haarqualitat [Testing the action of biotin on hair loss and hair quality]. Z. Hautkr. 67: 246-255; W. Gehring (1996) Der Einfluss von Biotin bei reduzierter Nagelqualitat. Eine
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plazebokontrollierte doppelblinde klinische Studie [The influence of biotin on reduced nail quality. A placebo-controlled double-blind clinical study]. Akt. Dermatol. 22: 20-25; U. Siebert et al. (1996) Zur Dosierung und Wirkung von Biotin bei Nagel- und Haarwachstumsstorungen [The dosage and action of biotin in nail and hair growth disorders]. Zeitschrift Hautnah 6: 438-443). It is known that topically applied biotincontaining formulations having a biotin content of 0.25% and 0.50% lead to a visible reduction in the development of wrinkles on the skin of old people (L. Gilli et al. (1995) Beeinflussung der Faltchenauspragung bei Altershaut durch topisch appliziertes Biotin [Influencing the development of wrinkles on the skin of old people by means of topically applied biotin]. Z. Hautkr. 70 (6): 419-425). In these investigations, it was not possible to show any epithelial and histopathological changes at all in the areas treated. Web site: http://www.delphion.com/details?pn=US06660251__ •
Genes encoding SCIP-1 orthologs and methods of use Inventor(s): Hendrick; Carol A. (Des Moines, IA), Hu; Xu (Urbandale, IA), Lu; Guihua (Urbandale, IA) Assignee(s): Pioneer Hi-bred International, Inc. (des Moines, Ia) Patent Number: 6,660,907 Date filed: July 10, 2001 Abstract: Compositions and methods for enhancing the resistance of plants to pests and for altering the level of biotin in plants are provided. Nucleotide sequences isolated from soybean, rice, maize, and wheat are provided. The nucleotide sequences encode orthologs of sunflower SCIP-1. Also provided are the SCIP-1 proteins encoded by such nucleotide sequences. The methods involve transforming plants with the SCIP-1 nucleotide sequences to enhance the plant's resistance to plant pests or to alter the level of biotin in the plant. Transformed plants, plant cells, tissues, and seeds are also provided. Excerpt(s): The invention relates to the genetic manipulation of plants, particularly to transforming plants with genes that enhance disease resistance. Throughout their lives, plants are routinely subjected to a variety of stresses, which act to impede or alter growth and development processes. Stresses to plants may be caused by both biotic and abiotic agents. For example, biotic causes of stress include infection with a pathogen, insect feeding, and parasitism by another plant such as mistletoe, and even grazing by ruminant animals. Abiotic stresses include osmotic stress, excessive light intensity or insufficient light intensity, cold temperatures, warm temperatures, synthetic chemicals such as those used in agriculture, and excessive wind. Because a stress negatively impacts plant growth and development processes, stress to agricultural plants has a negative economic impact expressed in the form of reduced yields, increased expenditures for pesticides or both. Developing crop plants that are better able to tolerate or even avoid stresses is desirable and will most certainly improve agricultural productivity. Given the world's both increasing human population and diminishing land area available for agriculture, improving agricultural productivity is a paramount challenge. A thorough understanding of the mechanisms used by plants to avoid or tolerate stresses may help in the development of new strategies for improving the stress tolerance of agricultural plants. Web site: http://www.delphion.com/details?pn=US06660907__
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High density array fabrication and readout method for a fiber optic biosensor Inventor(s): Albertson; Donna G. (Lafayette, CA), Gray; Joe (San Francisco, CA), Pinkel; Daniel (Walnut Creek, CA) Assignee(s): Medical Research Council (london, Gb), The Regents of the University of California (oakland, Ca) Patent Number: 6,417,506 Date filed: August 17, 2000 Abstract: The invention relates to the fabrication and use of biosensors comprising a plurality of optical fibers each fiber having attached to its "sensor end" biological "binding partners" (molecules that specifically bind other molecules to form a binding complex such as antibody-antigen, lectin-carbohydrate, nucleic acid-nucleic acid, biotinavidin, etc.). The biosensor preferably bears two or more different species of biological binding partner. The sensor is fabricated by providing a plurality of groups of optical fibers. Each group is treated as a batch to attach a different species of biological binding partner to the sensor ends of the fibers comprising that bundle. Each fiber, or group of fibers within a bundle, may be uniquely identified so that the fibers, or group of fibers, when later combined in an array of different fibers, can be discretely addressed. Fibers or groups of fibers are then selected and discretely separated from different bundles. The discretely separated fibers are then combined at their sensor ends to produce a high density sensor array of fibers capable of assaying simultaneously the binding of components of a test sample to the various binding partners on the different fibers of the sensor array. The transmission ends of the optical fibers are then discretely addressed to detectors--such as a multiplicity of optical sensors. An optical signal, produced by binding of the binding partner to its substrate to form a binding complex, is conducted through the optical fiber or group of fibers to a detector for each discrete test. By examining the addressed transmission ends of fibers, or groups of fibers, the addressed transmission ends can transmit unique patterns assisting in rapid sample identification by the sensor. Excerpt(s): This invention relates to the fabrication and use of biosensors comprising biological "binding partners" (molecules that specifically bind other molecules to form a binding complex such as antibody-antigen, lectin-carbohydrate, nucleic acid-nucleic acid, biotin-avidin, etc.) linked to optical fibers. Specifically, batches of optical fibers are mass processed with the same species of binding partner, singulated from their particular batch, regrouped with like optical fibers from other batches having other species of binding partners. Upon regrouping of the optical fibers, high density arrays are formed which can simultaneously interrogate samples for a multiplicity of analytes for sample identification and processing. Biosensors are sensors that detect chemical species with high selectivity on the basis of molecular recognition rather than the physical properties of analytes. See, e.g., Advances in Biosensors, A. P. F. Turner, Ed. JAI Press, London, (1991). Many types of biosensing devices have been developed in recent years, including enzyme electrodes, optical immunosensors, ligand-receptor amperometers, and evanescent-wave probes. Updike and Hicks, Nature, 214: 986 (1967), Abdel-Latif et al., Anal. Lett., 21: 943 (111988); Giaever, J. Immunol., 110: 1424 (1973); Sugao et al. Anal. Chem., 65: 363 (1993), Rogers et al. Anal. Biochem., 182: 353 (1989). Biosensors comprising a biological "binding molecule" attached to an optical fiber are well known in the prior art, most typically as evanescent wave detectors (see, for example, U.S. Pat. No. 4,447,546 to Hirschfeld and U.S. Pat. Nos. 4,582,809 and 4,909,990 to Block et al.). In order to maximize sensitivity and selectivity such biosensors typically utilize a single species of biological binding molecule affixed to the face of the sensor.
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Labeled vitamin D compounds and the use thereof Inventor(s): Holick; Michael F. (Sudbury, MA), Ray; Rahul (Wayland, MA) Assignee(s): A & D Bioscience, Inc. (sudbury, Ma) Patent Number: 6,455,714 Date filed: March 19, 2001 Abstract: Biotin, fluorescent and chemiluminescent labeled vitamin D compounds are disclosed as well as their use in assays for the presence of vitamin D, its metabolites and vitamin D analogs in biological fluids. Excerpt(s): The present invention relates to non-radioactive vitamin D compounds and methods to assay for the presence of vitamin D, vitamin D analogs and their metabolites which may be present in milk, blood or other biological fluids. The assay methods employed in this invention may be enzyme linked immunoassays (ELISAs) (with biotin containing compounds) and fluorimetric and chemiluminometric assays (with fluorescein or chemiluminiscence containing compounds). It is well-established that cutaneously synthesized vitamin D.sub.3, a seco-steroid, undergoes sequential metabolic conversions to 25-hydroxyvitamin D.sub.3 (25-OH-D.sub.3) in the liver and to 1,25(OH).sub.2 D.sub.3 in the kidney. 1,25(OH).sub.2 D.sub.3, the dihydroxylated metabolite of vitamin D.sub.3, is the most active form of vitamin D hormone which is intimately involved in calcium and phosphorous homeostasis (Holick, M. F. (1989), "Vitamin D: biosynthesis, metabolism and mode of action." In Endocrinology, vol. 2, Degroot et al. (eds.), Saunders, W. B., Philadelphia, pp. 902-926). In addition to vitamin D.sub.3 (synthesized in the skin), another chemical form of vitamin D.sub.3, called vitamin D.sub.2, exists in nature. Vitamin D.sub.2 is metabolized to 25-hydroxyvitamin D.sub.2 (25-(OH).sub.2 -D) and 1,25(OH).sub.2 D.sub.2 in a manner similar to vitamin D.sub.3. Vitamin D.sub.2 is obtained primarily from diet and vitamin D supplementation, and can be as little as 5-10%, or as high as 100% of the circulating concentration of 25-OH-D depending on the relative amounts of vitamin D.sub.2 present in the diet and cutaneously-produced vitamin D.sub.3 by exposure to sunlight (Holick, M. F. et al. (1986) "Calcium, phosphorus and bone metabolism: calcium regulating hormones," in Harrison's Principles of Internal Medicine, 13th Ed., Braunwald el aL (eds.), McGraw-Hill, New York, pp. 2137-2151). In the following discussion, it may be assumed that vitamin D, 25-OH-D and 125(OH).sub.2 D will represent the total pool of vitamin D and its metabolites, unless otherwise mentioned. Biosynthesis of 25-OH-D and 1,25(OH).sub.2 D and their metabolism are regulated by the factors that control mineral and skeletal metabolism (Holick, M. F. (1989)). As a result, the serum 1,25(OH).sub.2 D level is an important pathophysiological indicator in several diseases. For example, production of 1,25(OH).sub.2 D is strongly influenced by a number of diseases such as acquired or inherited disorders of vitamin D-metabolism, including renal osteodystrophy, certain metabolic bone diseases, sarcoidosis, hypercalcemia associated with chronic granulotomous disorders, and vitamin D-dependent rickets types I and II (Holick, M. F. et al. (1986)). Web site: http://www.delphion.com/details?pn=US06455714__
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Labelling and selection of molecules Inventor(s): Vaughan; Tristan John (Cambridge, GB), Derbyshire; Elaine Joy (Royston, GB), Johnson; Kevin Stuart (Caldecote Highfields, GB), McCafferty; John Gerald (Babraham, GB), Osbourn; Jane Katharine (Cambridge, GB) Assignee(s): Cambridge Antibody Technology Limited (cambridgeshire, Gb) Patent Number: 6,489,123 Date filed: January 23, 2001 Abstract: A method of labelling molecules which includes providing in a common medium a label molecule, a marker ligand able to bind a member of a specific binding pair, such as an antigen, a sbp member, an enzyme able to catalyze binding of the label molecule to other molecules, the enzyme being associated with the marker ligand; causing or allowing binding of the marker ligand to the sbp member; and causing or allowing binding of the label molecule to other molecules in the vicinity of the marker ligand bound to the sbp member. The marker ligand may be an antibody or any specific binding molecule, such as a chemokine or cytokine. A complementary member of the specific binding pair may be included, e.g. an antibody, or a diverse population of such sbp members, e.g. antibodies, may be included within which those which bind the counterpart sbp member, e.g. antigen, may be labelled and subsequently isolated for manipulation and/or use. Suitable labels include biotin-tyramine with signal transfer being catalysed by hydrogen peroxidase. Cells, virus particles and other moieties may be labelled, for identification or obtention of proteins which interact or are in close proximity with a particular sbp member, or of cells of interest, or for enhancement of labelling, e.g. for cell sorting. Excerpt(s): The present invention relates to labelling and selection of molecules, such as members of a specific binding pair (sbp) able to bind a complementary sbp member of interest, especially though not exclusively a complementary sbp member for which an existing ligand is available. In exemplary embodiments, the present invention relates to selection of antibodies, or polypeptides comprising an antibody antigen binding domain, specific for an antigen of interest for which an existing binding molecule, which may be an antibody, such as a monoclonal antibody, is already available. It involves deposition of a label or reporter molecule, such as biotin-tyramine, on molecules in the vicinity of a "marker ligand" which comprises for example a monoclonal antibody (specific for an antigen of interest) in association with an enzyme which catalyzes such deposition. Molecules labelled in accordance with the present invention may include binding members such as antibodies which bind the same binding target (e.g. antigen) as the marker ligand if such binding members are included in the reaction medium, the target molecule to which the marker ligand binds, which allows for identification and/or purification of unknown antigen targets, and/or other molecules in the vicinity of the binding target and/or the marker ligand when bound to its binding target, e.g. on a cell surface on which the binding target is found, including molecules complexed with the binding target, allowing for identification of novel protein-protein interactions. There are also various advantages in labelling cells or other particles using the present invention, especially when the process is reiterated to augment the extent of labelling. Further aspects and embodiments of the invention are disclosed herein. Numerous kinds of specific binding pairs are known, as epitomised by the pair consisting of antibody and antigen. Other specific binding pairs are discussed briefly infra and may equally be employed in the various aspects of the present invention disclosed herein. For convenience, however, most of the discussion herein refers to "antibody " as the type of (first) specific binding pair (sbp) member whose selection is sought in performance of
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methods of various embodiments of the invention, "antigen" as the complementary (second) sbp member of interest for which specific binding molecules may be sought to be selected and marker ligand as the pre-existing binding molecule known to be able to bind the complementary sbp member of interest. Generally, the marker ligand comprises an antibody antigen binding domain specific for the complementary sbp member of interest (e.g. antigen). Other suitable marker ligands include hormones, cytokines, growth factors, neuropeptides chemokines, enzyme substrates and any other specific binding molecule. Also present is a label or reporter molecule and an enzyme that catalyses binding of the label to other molecules in the vicinity. Bearing this in mind, the present invention (in some embodiments) can be said to have resulted from the inventors having identified a means to select for antibodies binding to an antigen, e.g. on cell surfaces, other solid supports, or in solution, using a marker ligand for the antigen to guide the recovery of antibodies binding in proximity to the marker ligand. This provides means to label molecules which bind in close proximity to a given defined ligand by transfer of a reporter molecule or label to the binding molecules. The defined ligand occupies a specific epitope on the antigen and generally blocks that particular epitope, and epitopes overlapping it, from binding other antibodies. Thus, antibodies which are selected for are usually those which do not bind to the marker ligand epitope, but are those which bind neighbouring epitopes. Antibodies which bind the same epitope as the original marker ligand may be obtained by an iterative process--using an antibody obtained in one round of the process as a second marker ligand in a further round--or by using appropriate conditions, as discussed further below. Web site: http://www.delphion.com/details?pn=US06489123__ •
Ligands added to adenovirus fiber Inventor(s): Curiel; David T. (Birmingham, AL), Engler; Jeffrey A. (Birmingham, AL) Assignee(s): Uab Research Foundation (birmingham, Al) Patent Number: 6,683,170 Date filed: July 13, 2001 Abstract: The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or strepavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence. Excerpt(s): The present invention generally relates to modification of the adenovirus fiber protein and methods for use thereof to modify cellular attachment by the fiber protein. In general, receptors are involved in pathways of endocytosis, either constitutive or ligand induced. These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes. The internalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation. Many receptors follow more than one
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intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration. Molecular and cellular mechanisms of receptor-mediated endocytosis is reviewed by Brown and Greene, DNA and Cell Biology 1991 10:6, 399-409. A number of viruses infect cells via a receptor-ligand interaction. Adenovirus is an example of a virus that utilizes receptor-mediated endocytosis to internalize infectious virus. Gene therapy requires transfer of recombinant nucleic acid constructs into cells. Although a number of different methods for gene transfer have been proposed, one of the most promising remains by utilizing recombinant viruses. The development of recombinant adenoviruses for this purpose has had a number of applications, based upon the unique advantages of this system. Web site: http://www.delphion.com/details?pn=US06683170__ •
Method for introduction of reporter groups into bacterial lipopolysaccharide-derived carbohydrates and the subsequent coupling of such derivatives onto solid surfaces Inventor(s): Boas; Ulrik (Copenhagen, DK), Heegaard; Peter M. H. (Copenhagen, DK), Jakobsen; Mogens Havsteen (Vanlose, DK), Stenbaek Jauho; Eva Irene (Copenhagen, DK) Assignee(s): Exiqon A/s (vedbaek, Dk) Patent Number: 6,436,653 Date filed: December 14, 1999 Abstract: The present invention provides a method for immobilizing a polysaccharide (PS) to a solid surface, said polysaccharide having a keto-carboxy group (--C(.dbd.O)-COOH) or a ketal or hemiketal group corresponding thereto, e.g. derived from KDO (2keto-3-deoxy-D-manno-octonic acid)), the method comprising the steps of: (a) forming a covalent bond between the carboxy group of the polysaccharide and a reporter molecule (RM), thereby forming a polysaccharide-reporter molecule conjugate (PS-RM), said reporter molecule comprising a recognition/substrate site (e.g. biotin or an anthraquinone); and (b) immobilizing the polysaccharide-report molecule conjugate by forming a specific bond (e.g. by photocoupling or formation of an affinity pair) between the recognition/substrate site of said reporter molecule and a reception/reagent site of the solid surface. The present invention also provides a solid surface thus obtainable and the use of such solid surfaces for diagnostic purposes, e.g. for the detection of bacterial infections from Gram-negative bacteria that are human or veterinary pathogens, e.g. enterobacteria, respiratory bacteria, urogenitial bacteria, and neuropathogenic bacteria such as Salmonella sp., Actinobacillus sp. Excerpt(s): The present invention relates to a method for immobilising special classes of polysaccharides to solid surfaces. Such a method is highly valuable in the construction of reliable assays for the detection of an antibody corresponding to the polysaccharide antigen. The present invention also relates to modified solid surfaces and to the use of such surfaces in various diagnostic assays. Furthermore, the present invention relates to novel KDO derivatives which are valuable intermediates in the construction of such modified solid surfaces. Bacterial lipopolysaccharides (LPSs) are characteristic outer membrane constituents of Gram-negative bacteria. LPSs are widely used as antigens in diagnostic assays specially designed for the specific detection of antibodies in serum, plasma, meat juice, saliva or other body fluids, originating from bacterial infections in humans and animals. LPSs are highly immunogenic and comprise one of the epitope characteristics for a given bacterial strain. In fact, the definition of a serotype is often based on the LPS and/or capsular polysaccharide (CPS) antigenicity. The antigenic
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specificity of the LPS molecule resides in the polysaccharide part of the LPS, the Oantigen, whereas the toxicity of the LPS is caused by residues contained in the lipid part of the LPS, called the lipid A. LPSs are highly amphiphilic compounds because of the joint presence of a hydrophilic O-polysaccharide group and a hydrophobic lipid group in the LPS molecule. Most of the characterised LPSs have the same principal structure which is especially conserved in the lipid A and in the inner core parts of the LPSs. The core is the part of the polysaccharide that comprises the bond between the O-antigen and the lipid A. This bond is invariably comprised of a ketosidic bond between the hemiketal function of the innermost KDO-residue and a hydroxyl-group of a GlcNAcresidue of the lipid A. The O-antigen of a specific bacterial serotype varies with respect to numbers of repeating units and may contain non-stoicheometrical substitutions with acetyl, phosphate, glycosyl or other groups. Generally, LPS-molecules without Oantigens, that is carrying only (parts of) the core saccharides in addition to the lipid A are called "rough" LPS, while LPS-molecules carrying O-antigens are called "smooth" (Raetz, C. R. H. in Escherichia coli and Salmonella: Cellular and Molecular Biology (Neidhardt, F. C. E. A., ed.) Vol. 1, 2nd Ed., pp. 1035-1063, American Society for Microbiology, Washington D.C., 1996; Hitchcock et al, 1986, J. Bacteriol. 166, 699-705). Previously, LPSs have generally been immobilised onto a solid surface without any modification of the molecules since the hydrophobic lipid A part of the molecules functions as a fairly efficient "anchor" binding the LPSs to the surface via non-covalent hydrophobic interactions leaving the hydrophilic O-polysaccharides pointing outward accessible for interactions with binding components, e.g. antibodies. However, it has been shown that the efficiency by which the LPSs are immobilised onto hydrophobic surfaces depends on both the nature of the surface and the equilibrium between free LPSs and formed LPS micelles. The equilibrium between free LPSs and formed LPS micelles depends on the amphiphilic nature of the LPSs and varies between LPSs from different bacteria strains as well as between different LPS serotypes. Certain types of LPSs have shown to be very difficult to immobilise onto solid surfaces by non-covalent bonds without addition of various micelle-dispersing agents (detergents) to the coating solution. Web site: http://www.delphion.com/details?pn=US06436653__ •
Method for producing biotin Inventor(s): Hauer; Bernhard (Fussgonheim, DE), Schroder; Hartwig (Nussloch, DE) Assignee(s): Basf Aktiengesellschaft (ludwigshafen, De) Patent Number: 6,436,681 Date filed: January 11, 2000 Abstract: A gene construct comprising a biotin gene having the sequence SEQ ID No. 1 or SEQ ID No. 3, organisms which comprise this gene construct, the use of these sequences or of the gene construct for preparing biotin, and a process for preparing biotin are described. Excerpt(s): This application is a 371 of International Application No. PCT/EP98/04097 published as WO 99/05285 which has an international filing date of Jul. 2, 1998. The invention relates to a gene construct comprising a biotin gene having the sequence SEQ ID No. 1 or SEQ ID No. 3, to organisms which comprise this gene construct, to the use of these sequences or of the gene construct for preparing biotin, and to a process for preparing biotin. Biotin (vitamin H) plays an essential role as coenzyme in enzymecatalyzed carboxylation and decarboxylation reactions. Biotin is thus an essential factor
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in living cells. Almost all animals and some microorganisms have to take biotin in from the outside because they are unable to synthesize biotin themselves. It is thus an essential vitamin for these organisms. Bacteria, yeasts and plants by contrast are themselves able to synthesize biotin from precursors (Brown et al. Biotechnol. Genet. Eng. Rev. 9, 1991: 295-326, DeMoll, E., Escherichia coli and Salmonella, eds. Neidhardt, F. C. et al. ASM Press, Washington D.C., USA, 1996: 704-708, ISBN 1-55581-084-5). Web site: http://www.delphion.com/details?pn=US06436681__ •
Multiflavor streptavidin Inventor(s): Cantor; Charles (Del Mar, CA), Reznik; Gabriel O. (Boston, MA), Sano; Takeshi (Needham, MA), Smith; Cassandra (Boston, MA), Vajda; Sandor (Medfield, MA) Assignee(s): The Trustees of Boston University (boston, Ma) Patent Number: 6,368,813 Date filed: March 23, 2000 Abstract: Compounds and methods are described for producing streptavidin mutants with changed affinities. In particular, modifications to the sequence of the natural streptavidin gene is described to create amino acid substitutions resulting in greater affinity for biotin substitutes than for biotin. Excerpt(s): The present invention relates to compounds and methods, and in particular, modified streptavidin having affinity for biotin substitutes. The biological sciences have been employed since early times by mankind to modify living organisms or their constitutive elements for a variety of purposes, such as the production of foods and therapeutic agents. However, only during the last fifty years there has been progress at the genetic level to gain a much better understanding of the essential component of living systems. This has led to the understanding that nucleic acids, in the form of DNA and RNA, store and distribute genetic information that determines the sequences of amino acids that characterize proteins; proteins contribute to the structure of an organism and execute most of the tasks required for its function and that even proteins form part of the mechanism by which they are synthesized (e.g. chaperones); polysaccharides, linear and branched polymer of sugars, provide structural elements, store energy, and when combined with peptides or proteins play an important role in cellular recognition; lipids, which include molecules such as fatty acids, phospholipids, and cholesterol, serve as energy sources and are the most important components of the membrane structures that organize and compartmentalize cellular function. However, proteins are the biological macromolecules with the greatest functional diversity. Proteins catalyze most reactions that occur in living cells, or serve as inhibitors of enzymatic reactions. They transport oxygen, electrons and energy to specific regions in the cell. Other proteins protect living organisms by recognizing and binding to foreign substances. There are also proteins that have a structural function such as collagen, the main constituent of connective tissue fibrils and bones, or have functional roles such as actin or myosin, which are involved in muscle dynamics. Web site: http://www.delphion.com/details?pn=US06368813__
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Multi-vitamin and mineral supplement Inventor(s): Cooper; Kenneth H. (Dallas, TX), Grundy; Scott Montgomery (Dallas, TX), Jialal; Ishwarlal (Dallas, TX), Selhub; Jacob (Brookline, MA), Willett; Walter Churchill (Cambridge, MA) Assignee(s): Cooper Concepts, Inc. (dallas, Tx) Patent Number: 6,361,800 Date filed: April 13, 2000 Abstract: This invention is directed to a multi-vitamin and mineral supplement which supplies the right amount of the right micronutrients at the right time to assure adequate intake of micronutrients needed for disease prevention and protection against nutritional losses and deficiencies due to lifestyle factors and common inadequate dietary patterns. The multi-vitamin and mineral supplement is comprised of vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, niacinamide, vitamin B6, vitamin B12, biotin, pantothenic acid, iron, phosphorus, iodine, magnesium, zinc, selenium, copper, chromium, potassium, choline, lycopene, and co-enzyme Q-10. Excerpt(s): This invention relates to multi-vitamin and mineral supplements. In particular, this invention relates to multi-vitamin and mineral supplements for improving health by insuring adequate intake of micronutrients needed for disease prevention and protection against nutritional losses and deficiencies due to such factors as lifestyle patterns and common inadequate dietary patterns. Vitamin and mineral preparations are commonly administered to treat specific medical conditions or as general nutritional supplements. Micronutrients are elements or compounds which are present in foods in small or trace amounts and includes vitamins, minerals, or other elements, and compounds found in foods for which a Recommended Daily Allowance (RDA) has not yet been determined. The macronutrients consist of carbohydrates, fats, and proteins which supply nutrients and calories. Some elements such as calcium, sodium, potassium, chloride, and phosphorus are consumed in relatively large amounts, while many such as iron, iodine, and zinc are consumed in small amounts. vitamins such as B12 and folic acid and the minerals cooper, selenium, and chromium are consumed in very small or trace amounts. In as much as the human body does not synthesize many compounds which are essential to the human body, these specific vitamins and minerals can be obtained from only two sources: food and supplements. The primary source of all nutrients is food. However, the majority of people do not meet the RDA of the foods containing these essential compounds and elements. Thus vitamin and mineral supplementation has become a recognized method of meeting accepted medical and health standards. An international panel of diet and cancer experts announced in London on Sep. 30, 1997, that as many as 30 to 40 percent of all cancer cases worldwide--3 to 4 million a year--could be avoided if people ate a healthy diet and got enough exercise. USA Today, Oct. 1, 1997. However, for some nutrients, the amounts proposed as being healthy apparently cannot be provided by a reasonable quantity and variety of natural foods. Thus nutrient supplements may be important for health promotion and prevention of chronic diseases. Journal of the American Medical Association, May 7, 1997. Web site: http://www.delphion.com/details?pn=US06361800__
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Nutritional composition made from conventional foods for mixing onsite in a blender and treating patients with hepatic disorders Inventor(s): Muszynska; Julia (108 Center St., Staten Island, NY 10306) Assignee(s): None Reported Patent Number: 6,524,610 Date filed: February 26, 2001 Abstract: A nutritional composition made from conventional food mixed on-site in a blender and treating patients with hepatic disorders. The composition includes a vitamin A enriched conventional food, a vitamin D enriched conventional food, a vitamin E enriched conventional food, a vitamin K enriched conventional food, a vitamin C enriched conventional food, a thiamine enriched conventional food, a riboflavin enriched conventional food, a niacin enriched conventional food; a pyridoxine enriched conventional food, a folic acid enriched conventional food, a pantothenic acid enriched conventional food, a vitamin B12 enriched conventional food, a biotin enriched conventional food, a chloine enriched conventional food, a sodium enriched conventional food, a potassium enriched conventional food, a chlorine enriched conventional food, a calcium enriched conventional food, a phosphorus enriched conventional food, a magnesium enriched conventional food, a copper enriched conventional food, an Iodine enriched conventional food, a manganese enriched conventional food, and a zinc enriched conventional food. Excerpt(s): The present invention relates to a nutritional composition. More particularly, the present invention relates to a nutritional composition made from conventional foods for mixing on site in a blender and treating patients with hepatic disorders. The liver, and its proper functioning, is of utmost importance to the survival of a patient. Because it is responsible for the metabolism of nearly all nutrients, and is the primary site for the inactivation of numerous toxins, the liver is one of the most important organs of the body. For example, the liver accounts for approximately 20% of the body's basal metabolism. The liver extracts a majority of the amino acids, carbohydrates, lipids, vitamins, and minerals from portal circulation. These nutrients, extracted by the liver, are used as substrates or cofactors in all metabolic processes carried out in the liver. Synthesis of plasma proteins and bile secretion are additionally important processes carried out by the liver. Web site: http://www.delphion.com/details?pn=US06524610__
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Nutritional system for nervous system disorders Inventor(s): Foreman; David J. (Chesterfield, VA) Assignee(s): C & D Foreman, Inc. (chesterfield, Va) Patent Number: 6,399,114 Date filed: May 24, 2001 Abstract: A novel composition for treating nervous system disorders. The composition is formed by preparing a mixture comprising an effective amount of vitamin B-6, folic acid, vitamin C, magnesium, vitamin B-3, copper, probiotics, fructo-oligosaccharide (FOS), betaine, pancreatin, papain, pepsin, vitamin B-1, vitamin B-2, vitamin B-12, biotin, pantothenic acid, chromium polynicotinate and a digestive support ingredient selected from the group consisting of dandelion root, juniper, aloe vera, burdock, ginger
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root, artichoke, and kelp. Other ingredients may include: beta carotene, vitamin E, selenium, zinc, sea vegetation, alfalfa, trace minerals and molybdenum. Excerpt(s): The present invention pertains to the field of nutritional formulas. Specifically, the present invention pertains to an improved formula for nervous system disorders. There are many disorders that affect the proper functioning of the nervous system. Examples of these disorders include autism, ADD, ADHD, hyperactivity disorder, and depression. People who suffer from these disorders often have common secondary symptoms including allergies, sluggish digestion, weak immune function and poor diet. Treatment for these various nervous system disorders include the use of synthetic drugs. Specifically, for ADD and ADHD mild central nervous system stimulant drugs such as Ritalin.RTM., Cylert.RTM. and Dexedrine.RTM. have been used. These drugs are not always successful. Moreover, such drugs may lead to undesirable side effects such as loss of appetite, insomnia, headaches, stomachaches, drowsiness and cardiac arrhythmia. Web site: http://www.delphion.com/details?pn=US06399114__ •
Polynucleotide portions of the biotin operon from B. subtilis for use in enhanced fermentation Inventor(s): Hohmann; Hans-Peter (Upper Montclair, NJ), Mouncey; Nigel John (Verona, NJ), Schlieker; Heinrich Winfred (Bloomfield, NJ), Stebbins; Jeffrey W. (Nutley, NJ) Assignee(s): Roche Vitamins, Inc. (parsippany, Nj) Patent Number: 6,656,721 Date filed: August 8, 2000 Abstract: The present invention provides a process for producing a target fermentation product. This process includes providing a fermentation medium containing a recombinantly-produced microorganism that over-produces a fermentation product and contains a mutation which causes auxotrophic growth of the microorganism wherein the auxotrophy within the microorganism does not compromise the ability of the microorganism to produce the fermentation product. The medium is then supplied in excess with all substrates required for production of the fermentation product and in growth limiting amounts with a substrate complementing the auxotrophy. Host cells, vectors, and polynucleotide sequences used in the process are also provided. The polynucleotide sequences of the present invention include sequences derived from the biotin operon of B. subtilis, and in particular the bioFDB gene cassette. Excerpt(s): The present invention relates to a process for producing a target fermentation product. More particularly, the present invention relates to a process for over-producing a target fermentation product in a microorganism having a mutation which causes auxotrophic growth of the microorganism, but that does not compromise its ability to over-produce the target fermentation product. Host cells and polynucleotide sequences used in the process are also provided. Many commercially valuable products are produced by fermentation reactions. For example, riboflavin, which is an essential vitamin that is required by all bacteria, animals, and plants, is synthesized by plants and bacteria, however, it cannot be produced by higher animals, which must acquire it from their diet. Riboflavin is produced commercially for use as a food and feed additive by, for example, fermentation reactions using Ashbya govsypii, Eremothecium ashbyii, or Candida flareri cells. (See e.g., Ainsworth, G. C. and Sussman,
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A. S., The Fungi, Academic Press, New York (1965); Heefner, D. L., et al., WO 88/09822; Hickey, R. J., Production of Riboflavin by Fermentation, in Industrial Fermentation (Underkofler, L. A. and Hickey, R. J., eds.) pp. 157-190, Chemical Publishing Co., New York (1954); and Perlman, D., et al., Fermentation Ind. Eng. Chem. 44:1996-2001 (1952). Web site: http://www.delphion.com/details?pn=US06656721__ •
Process for the fermentative preparation of L-amino acids using coryneform bacteria Inventor(s): Eggeling; Lothar (Julich, DE), Eikmanns; Bernd (Ulm, DE), Mockel; Bettina (Bielefeld, DE), Pfefferle; Walter (Halle, DE), Sahm; Hermann (Julich, DE), Tilg; Yvonne (Mettmann, DE) Assignee(s): Degussa AG (dusseldorf, De) Patent Number: 6,379,934 Date filed: July 29, 1999 Abstract: The invention provides a process for the fermentative preparation of L-amino acids using coryneform bacteria, in which the subunit carrying the biotin-carboxyl carrier protein domain and the biotin-carboxylase domain of the nucleotide sequence encoding the enzyme acetyl-CoA carboxylase (accBC gene) is amplified, in particular is overexpressed. Excerpt(s): The invention provides a process for the fermentative preparation of Lamino acids, in particular lysine, using coryneform bacteria in which the accBC gene is amplified. L-amino acids, in particular L-lysine, are used in animal nutrition, in human medicine and in the pharmaceutical industry. It is known that these amino acids are prepared by fermentation using strains of coryneform bacteria, in particular Corynebacterium glutamicum. Due to the high degree of importance of these products, a constant effort is made to improve the method of preparation. Process improvements may be based on fermentation engineering steps such as, for example, stirring and supplying with oxygen, or the composition of the nutrient medium such as, for example, the concentration of sugar during fermentation, or the working up process aimed at obtaining the product itself by, for example, ion-exchange chromatography or the intrinsic power of the microorganism itself. Web site: http://www.delphion.com/details?pn=US06379934__
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Process to control the molecular weight and polydispersity of substituted polyphenols and polyaromatic amines by enzymatic synthesis in organic solvents, microemulsions, and biphasic systems Inventor(s): Akkara; Joseph A. (Holliston, MA), Ayyagari; Madhu (Brighton, MA), Kaplan; David L. (Stow, MA) Assignee(s): The United States of America AS Represented by the Secretary of the Army (washington, Dc) Patent Number: 6,362,314 Date filed: February 4, 1999 Abstract: A process of controlling the molecular weight and dispersity of poly(pethylphenol) and poly(m-cresol) synthesized enzymatically by varying the composition of the reaction medium. Polymers with low dispersities and molecular weights from
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1000 to 3000 are synthesized in reversed micelles and biphasic systems. In comparison, reactions in bulk solvents resulted in a narrow range of molecular weights (281 to 675 with poly(p-ethylphenol) in a DMF/water system and 1,400 to 25,000 with poly(mcresol) in an ethanol/water system). Poly(p-ethylphenol) was functionalized at hydroxyl positions with palmitoyl, cinnamoyl, and biotin groups. Excerpt(s): The present invention relates generally to the preparation of phenolic and aromatic amine polymers, wherein the reaction conditions are controlled such that high product yields, molecular weight, and a uniform molecular weight distribution are obtained. Phenolic and aromatic amine polymer resins constitute a very important and useful class of chemical compounds. They have a number of uses, e.g., as coatings and laminates that provide a number of functional advantages. Besides possessing good thermal properties, these polymers can be doped to make them electrically conductive, making them a key component of integrated circuit (IC) chips. At present, these polymers are prepared by chemical synthesis, e.g., as from phenol and formaldehyde. The polymers's linearity/network structure (and, by extension, their functional properties) varies depending on the monomer and type of reaction conditions used. However, the use of certain constituent chemicals, such as formaldehyde, is being restricted in the chemical industry because of their toxicity. Accordingly, the enzymemediated synthesis of polyphenols and polyaromatic amines offers a viable alternative to the currently used chemical synthesis of such commercial phenolic resins. Web site: http://www.delphion.com/details?pn=US06362314__ •
Purification of oligomers Inventor(s): Sproat; Brian S. (Adelebsen, DE) Assignee(s): Ribozyme Pharmaceuticals, Inc. (boulder, Co), Yale University (new Haven, Ct) Patent Number: 6,410,225 Date filed: June 27, 1997 Abstract: Compositions and methods are disclosed which facilitate purification of oligomers and other compounds. The disclosed compositions are silyl compositions that can be directly coupled, or coupled through a linking group, to a compound of interest, preferably to an oligomer at the end of oligomer synthesis. The silicon atom includes between one and three sidechains that function as capture tags. In one embodiment, the capture tags are lipophilic, which allows a derivatized oligomer to be separated from failure sequences by reverse phase chromatography. In another embodiment, the capture tags are compounds with a known affinity for other compounds, which other compounds are preferably associated with a solid support to allow chromatographic separation. Examples include haptens, antibodies, and ligands. Biotin, which can bind to or interact with a streptavidin-bound solid support, is a preferred capture tag of this type. Excerpt(s): The disclosed invention is in the general field of oligonucleotide synthesis and purification. Oligonucleotides are being pursued as therapeutic and diagnostic agents. Examples of such oligonucleotides include antisense oligonucleotides, aptamers, triplex forming agents, external guide sequences, catalytic oligomers, and ribozymes. Synthetic oligonucleotides based on oligo(2'-O-allylribonucleotide)s which can cleave, or induce cleavage of, specific RNA molecules are showing great promise as a new class of rationally designed therapeutics. Such chemically modified oligonucleotides are useful
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for cleaving an unwanted or overexpressed RNA in a highly specific fashion, thus preventing the synthesis of the corresponding protein which is causative for a particular disease state. Such an oligonucleotide having RNA cleaving activity has been successfully used in mice (Lyngstadaas et al., EMBO Journal 14:5224-5229 (1995)). Several other examples of such compounds have been shown to possess reasonable pharmacokinetics (Desjardins et al., J. Pharmacol. Exp. Ther. 278:1419-1427 (1966)). Versions of these compounds that are stable enough for in vivo applications, yet have reasonable catalytic activity, contain five residual purine ribonucleotides at critical positions in the hammerhead catalytic core and are generally in the range of 34 to 38 residues in length (Lyngstadaas et al., EMBO Journal 14:5224-5229 (1995)). Synthetic methods for preparing oligonucleotides generally include solid phase synthesis using phosphoramidite coupling chemistry. This chemistry generally involves coupling the 3'hydroxy group of a first nucleotide to a solid support, and reacting the 5'-hydroxy group with subsequent monomers containing protected 5'-hydroxy groups. After each coupling step, the 5'-protecting group is removed, freeing up a subsequent 5'-hydroxy group for subsequent coupling with an additional monomer. The coupling chemistry has a relatively high yield for each step, but about one to two percent of the hydroxy groups are not successfully coupled at each step in the synthesis. These un-reacted hydroxy groups must be prevented from further reactions, to avoid the preparation of unwanted sequences. To accomplish this, the hydroxy groups are capped, for example, using acetic anhydride. The capped sequences are typically referred to as failure sequences. Web site: http://www.delphion.com/details?pn=US06410225__ •
Recombinant inactive avidin mutants Inventor(s): Brandstetter; Hans (Chelsea, DE), Deger; Arno (Pernzberg, DE), Engh; Richard (Munchen, DE), Kopetzki; Erhard (Penzberg, DE), Muller; Rainer (Penzberg, DE), Schmitt; Urban (Oberhausen, DE) Assignee(s): Roche Diagnostics Gmbh (mannheim, De) Patent Number: 6,391,571 Date filed: August 4, 1999 Abstract: The present invention concerns muteins of avidin and streptavidin with a reduced binding affinity for biotin as well as their use as interference elimination reagents in methods for the determination of an analyte e.g. in diagnostic tests such as for example immunoassays and nucleic acid hybridization assays. In addition the invention concerns the use of muteins of avidin and streptavidin as systems capable of regeneration for binding biotin e.g. for the analysis of biotinylated molecules, for examining receptor ligand interactions as well as for the affinity purification of biotinylated molecules. Excerpt(s): The present invention concerns muteins of avidin and streptavidin with a reduced binding affinity for biotin as well as their use as interference elimination reagents in methods for the determination of an analyte e.g. in diagnostic tests such as immunoassays and nucleic acid hybridization assays. In addition the invention concerns the use of muteins of avidin and streptavidin as systems that can be regenerated for binding biotin for example for the analysis of biotinylated molecules, for investigating receptor-ligand interactions as well as for the affinity purification of biotinylated molecules. In detection methods for the determination of analytes such as immunoassays and nucleic acid hybridization assays the analytes are often determined
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by means of high affinity interaction between the partners of a specific binding pair. A typical example for a specific binding pair is the avidin/streptavidin-biotin complex. When using the avidin/streptavidin-biotin binding pair its high binding affinity is used. In this process a solid phase coated with avidin/streptavidin is for example used to which a biotinylated complex of analyte and specific receptor can bind. In other test formats avidin/streptavidin can also be used in a soluble form. However, apart from specific interactions. side reactions often also occur such as for example undesired interactions and unspecific binding reactions between the test components and additional components present in the sample or on the solid phase. In particular other substances present in the sample often bind to immobilized or soluble avidin and streptavidin and thereby cause false positive or false negative test results. Furthermore these interactions can also cause an increase in the background signal and an increased scattering of the signals which decreases the sensitivity and specificity of the respective test. Web site: http://www.delphion.com/details?pn=US06391571__ •
Recombinant streptavidin-metallothionein chimeric protein having biological recognition specificity Inventor(s): Cantor; Charles R. (Berkeley, CA), Glazer; Alexander N. (Orinda, CA), Sano; Takeshi (Albany, CA) Assignee(s): The Regents of the University of California (oakland, Ca) Patent Number: 6,391,590 Date filed: October 21, 1991 Abstract: Streptavidin-metallothionein chimeric proteins with biological recognition specificity in which the streptavidin moiety provides high affinity biotin binding and the metallothionein moiety provides a high affinity metal binding. The binding affinity of the streptavidin-metallothionein chimeric protein both for biotin and heavy metal ions allows specific incorporation into, conjugation with, or labelling of any biological material containing biotin with various heavy metal ions. Excerpt(s): This invention concerns streptavidin-metallothionein chimeric proteins which possess biological recognition specificity. Recombinant streptavidinmetallothionein chimeric proteins containing various metal ions are molecules which have a great potential in preventive and therapeutic medicine in both humans and animals as well as for diagnostic use. While each individual molecule, i.e., streptavidin and metallothionein have been known and described previously, their composite molecule has never before been constructed. Biochemistry of metallothionein, particularly its amino acid sequence in various species, its metal binding sites, metal thiolate clusters and spatial structures are described in Biochemistry, 27:509 (1988). Ann. Rev. Biochem., 55:913 (1986) is directed to the gene structure, organization, amplification and transcriptional regulations, and describes also some genetic engineering applications, such as for example, metallothionein-rat growth hormone and metallothionein-human growth hormone genes expressed in transgenic mice, or conferring resistance to copper toxicity via the CUP 1 copper-metallothionein gene. Web site: http://www.delphion.com/details?pn=US06391590__
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Regenerable biosensor electrochemical control
using
total
internal
reflection
fluorescence
with
Inventor(s): Asanov; Alexander N. (Starkville, MI), Oldham; Philip B. (Starkville, MI), Wilson; W. William (Starkville, MI) Assignee(s): The Uab Research Foundation (birmingham, Al) Patent Number: 6,511,854 Date filed: June 12, 2000 Abstract: An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface (118), the improvement comprising: applying the electrical potential to the waveguide surface (118) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/antiantibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface (118). Excerpt(s): This invention relates generally to a diagnostic apparatus and to related methods for using that apparatus in rapidly analyzing samples for analytes of interest, and more particularly to an apparatus and associated methods which provide simultaneous fluorescence detection and electrochemical control of biospecific binding. Investigation of the interactions between biomolecules has attracted increasing attention in recent years. An understanding of these interactions and the ability to control them are critical for a variety of objectives, such as the determination of structure-function relationships and protein crystallogenesis, drug design and development of targeted drug delivery systems, and biomolecular engineering and design of biosensors. Total internal reflection fluorescence (hereinafter "TIRF") techniques have proven to be wellsuited for investigating biomolecular interactions. Such techniques generally utilize optical waveguides, either planar or cylindrical, having a portion of one surface of the waveguide carrying an immobilized binding agent, such as a specific binding partner (e.g., an antibody or antibody fragment). A light beam is introduced into the waveguide wherein the light beam travels in the waveguide. The light beam is totally internally reflected at the interface between the waveguide and a surrounding medium having a lower refractive index than the waveguide. A portion of the electromagnetic field of the internally reflected light beam penetrates into the surrounding medium and forms an evanescent light field. The intensity of evanescent light drops off substantially exponentially with increasing distance from the waveguide surface. In a fluoroimmunoassay, evanescent light can be used to selectively excite tracer molecules directly or indirectly bound to the immobilized binding agent, while tracer molecules free in solution beyond the evanescent light penetration distance are not excited and thus do not contribute "background" fluorescence. The use of evanescent field properties for fluorescence measurements is sometimes referred to as evanescent sensing. For a glass or a similar silica-based material, or an optical plastic such as polystyrene, with the surrounding medium being an aqueous solution, the region of effective excitation by evanescent light generally extends about 1000 to 2000.ANG. (angstroms) from the waveguide surface. This depth is sufficient to excite most of the tracer molecules bound to the capture molecules (antibodies, receptor molecules, and the like, or fragments thereof) on the waveguide surface, without exciting the bulk of the tracer molecules that
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remain free in solution. The resulting fluorescence reflects the amount of tracer bound to the immobilized capture molecules, and in turn the amount of analyte present in the aqueous solution. Web site: http://www.delphion.com/details?pn=US06511854__ •
Serum free medium for chondrocyte cells Inventor(s): Cancedda; Ranieri (Genoa, IT), Dozin; Beatrice (Rapallo, IT) Assignee(s): Consorzio Per LA Gestione Del Centro DI Biotechnologie Avanzate (genoa, It), Istituto Nazionale Per LA Ricerca Sul Cancro (genoa, It) Patent Number: 6,617,159 Date filed: June 11, 2001 Abstract: Serum free media for growth and proliferation of chondrocytes and mesenchymal stem cells in culture are provided. A serum free medium for growth of chondrocytes includes a serum free composition comprising FGF-2, linoleic acid, ascorbic acid, B-mercaptoethanol, transferrin and dexamethasone. Further the composition comprises EGF, PDGFbb, insulin and albumin. A method for growing chondrocytes in a serum free medium comprising the composition is also provided. Also provided for mesenchymal stem cell growth, is a serum free medium which includes a composition comprising FGF-2, LIF, SCF, pantotenate, biotin and selenium and method, therefore. Excerpt(s): Bone and cartilage transplantation is an absolute need in reconstruction of bone and cartilage segments in plastic surgery, traumatic surgery or after the removal of neoplastic lesions, etc. Typically, material of human (autologous, from donors or from cadavers) or animal origin has been used for this purpose. Given the increased demand from clinicians for transplant tissues, the increased need for microbial safety in tissue transplantation, the advances in cell biology, cell differentiation and tissue engineering, the concept of rebuilding tissues from autologous or allogeneic cells expanded in vitro has become a growing field in the world of biomedical sciences. Cellular sources for skeletal repair include chondrocytes and cells committed to the chondrocyte lineage, and mesenchymal stem cells, the former specific for cartilage, the latter multipotential and therefore having the potential to be used to replace bone, cartilage and other tissues. Mesenchymal stem cells (MSCs) are found in bone marrow as well as in blood, dermis and periosteum. Although these cells are normally present at very low frequencies in bone marrow, these cells can be isolated purified and culturally expanded, for example, as described in U.S. Pat. No. 5,486,359. Typically, the ill vitro expansion of chondrocytes and MSCs takes place in culture medium supplemented with bovine serum or optimally with autologous serum from the patient. However, the presence of animal or autologous serum in chondrocyte and MSC cultures has certain disadvantages and limitations in view of the potential therapeutical applications of these cultures. Web site: http://www.delphion.com/details?pn=US06617159__
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Streptavidin mutants having secondary functional domains Inventor(s): McDevitt; Todd C. (Seattle, WA), Nelson; Kjell E. (Seattle, WA), Stayton; Patrick S. (Seattle, WA) Assignee(s): University of Washington (seattle, Wa) Patent Number: 6,413,934 Date filed: August 25, 1999 Abstract: Streptavidin molecules are disclosed that contain a secondary functional domain. In preferred embodiments, the secondary domain is a cell adhesion peptide incorporated in the streptavidin amino acid sequence at a site not interfering with biotin binding. In a preferred embodiment, the cell adhesion peptide is arginine-glycineaspartate (Arg-Gly-Asp) (RGD). The peptide is preferably placed on an exposed loop of the streptavidin molecule, such as within the loop defined by residues 63 to 69. The mutant streptavidin molecule can have other characteristics such as reduced biotin binding due to a modification of an amino acid at the biotin binding site. Preferred uses for the disclosed streptavidin molecules are as adaptors to bring, via a streptavidin/biotin interaction, the secondary functional domain into proximity with a cell or molecule to be affected and as a coating for substrates such as vascular devices or prostheses. Excerpt(s): The present invention is directed to streptavidin molecules having secondary functional domains such as a cell adhesion domain. Streptavidin, a protein produced by Streptomyces avidinii, forms a very strong and specific non-covalent complex with the water soluble vitamin biotin. Streptavidin is a tetrameric protein that binds biotin with an affinity that is among the highest displayed for non-covalent interactions between a ligand and protein, with an association constant (Ka) estimated to be in the range of 10.sup.13 M.sup.-1 to 10.sup.15 M.sup.-1. This binding affinity is strong enough to be essentially irreversible under normal physiological solution conditions, and provides the basis for streptavidin and biotin's usefulness in a wide variety of clinical and industrial applications. See, Green, Adv. Prot. Chem. 29:85-143 (1975). Both streptavidin and the homologous protein avidin, which shares its high affinity for biotin, have been studied as paradigms of strong ligand-protein interactions. The X-ray crystal structures of streptavidin and avidin, both in their apo and holo forms, have been described. The sequences of both have also been reported, as have the construction of several streptavidin fusion proteins (Sano and Cantor, Biochem. Biophys. Res. Commun. 176:571-577 (1991); U.S. Pat. No. 4,839,293). Web site: http://www.delphion.com/details?pn=US06413934__
•
Substituted 2-[-6-benzyl-5-oxo-3-phenyl-(3s,7s, c][1,3]thiazol-7yl] compounds
7aR)-perhydroimidazol[1,5-
Inventor(s): Chavan; Subhash Prataprao (Maharashtra, IN), Chittiboyina; Amar Gopal (Maharashtra, IN), Kalkote; Uttam Ramrao (Maharashtra, IN), Kamat; Subhash Krishnaji (Maharashtra, IN), Ravindranathan; Thotapallil (Maharashtra, IN) Assignee(s): Council of Scientific and Industrial Research (new Delhi, In) Patent Number: 6,486,328 Date filed: October 12, 2000
Patents 159
Abstract: A novel route has been developed for substituted 2-[-6-benzyl-5-oxo-3-phenyl(3s,7s,7aR)-perhydroimidazol[1,5-c][1,3]thiazo l] compounds; crucial intermediates for D(+)-biotin of formula (7) which involves simple, efficient, practical and cost effective protocol. These are crucial intermediates for commercially important D(+)-biotin preparation. These compounds are more stable and are produced by non-hazardous methods. Excerpt(s): D(+) Biotin is prepared in the prior art from amino acids viz., cysteine, cyctine and serine. These processes involving L-cystine as the precursor, incorporate intramolecular radical cyclization (E. J. Corey, M. M. Mehrotra, Tet.Lett., 29, 57 1988) as the key step is construct the tetrahydrothiophene moiety of biotin. Another prior art process involves intramolecular cycloaddition (3+2) of derivatives of L-cystine (E. G. Baggiolini, H. L. Lee, G. Pizzolato and M. R. Uskokovic, J.Am.Chem.Soc., 104, 6460, 1982), and L-cysteine (, H. L. Lee, E. G. Baggiolini and M. R. Uskokovic, Tetrahedron 43, 4887, 1987). In another process starting from L-cysteine, a bicyclic imidazolidine is the key intermediate leading to D(+)-biotin (E. Poetsch and M. Casutt, EP 242,686 1986 CA:108:1612077k 1988; Chimia 41, 148 1987). In an totally different and novel approach. L-cysteine was converted to its thiazolidine derivative which on treatment with bromine is converted stetreospecifically to a bicyclic intermediate as a single stereoisomer and eventually transformed to D(+)-biotin (P. N. Confalone, E. G. Baggiolini, D. Lollar, and M. R. Uskokovic, J. Am. Chem. Soc., 99, 7020 1977). Process for stereospecific synthesis of D(+)-Biotin from sugars of suitable configuration are known. [From Mannose Tet. Lett., 32, 2765 1975]. Web site: http://www.delphion.com/details?pn=US06486328__ •
Wildlife nutritional supplement Inventor(s): Fuhr; David R. (Winigan, MO), Hauser; David (Winigan, MO) Assignee(s): 4 Seasons Wildlife Nutrition, Llc (winigan, Mo) Patent Number: 6,572,903 Date filed: May 8, 2002 Abstract: The present invention is a wildlife nutritional supplement for free ranging ruminants including about 7.5-8.5% calcium, about 3.5% phosphorus, about 32-37% salt, at least one "B" series vitamin is selected from a group consisting of pantothenic acid, folic acid, riboflavin, niacin, thiamine, cobalamin, and pyridoxine hydrocholoride, about 16-19% sodium, about 0.15% magnesium, about 0.15% potassium, about 2.5% sulfur, about 1,200 PPM iron, about 20 PPM copper, about 105 PPM manganese, about 45 PPM zinc, about 5 PPM cobalt, about 1 PPM selenium, about 1 PPM iodine, about 50,000 IU/LB Vitamin A, about 20,000 IU/LB Vitamin D, about 50 IU/LB Vitamin E, about 134 MG/LB biotin, about 60 MG/LB ascorbic acid, oxytetracycline and fenbendazole. Excerpt(s): This invention relates to wildlife nutritional supplements, and more particularly to a ruminant feed supplement having enhanced palatability and immunesystem bolstering effects. The reduction of habitat due to human development has left a noticeable impact on the health and vitality of wild ruminant animals. Ruminant animals such as deer, elk and the like, suffer diminished reproduction, decreased weight, smaller antlers, and susceptibility to disease and parasites. There are seven major minerals that have an important effect on wildlife: (1) calcium aids in the growth of bones, teeth and antlers and is important in the function of muscles and nerves; (2) phosphorus aids in the growth of bones, teeth and antlers, enhances energy metabolism
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and enzymation as well as proper protein utilization; (3) potassium is integral in the function of nerves, enzyme processes, as well as mineral and water balance; (4) sulfur is an essential component of some proteins; (5) sodium is vital to the function of muscles and nerves and also maintains water balance; (6) chloride of sodium forms hydrochloric acid in the abomasums which aids in protein breakdown; and (7) magnesium is an important component is almost all body processes. Web site: http://www.delphion.com/details?pn=US06572903__
Patent Applications on Biotin As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to biotin: •
22325, a human biotin-requiring enzyme family member and uses therefor Inventor(s): Tsai, Fong-Ying; (Newton, MA) Correspondence: Steven A. Bossone; Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030096276 Date filed: August 20, 2002 Abstract: The invention provides isolated nucleic acids molecules, designated 22325 nucleic acid molecules, which encode novel biotin-requiring enzyme family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 22325 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 22325 gene has been introduced or disrupted. The invention still further provides isolated 22325 proteins, fusion proteins, antigenic peptides and anti-22325 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided. Excerpt(s): The present invention relates to an enzyme belonging to the superfamily of biotin-requiring enzymes. The invention also relates to polynucleotides encoding the enzyme. The invention further relates to methods using the enzyme polypeptides and polynucleotides as a target for diagnosis and treatment in enzyme-mediated disorders. The invention further relates to drug-screening methods using the enzyme polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the enzyme polypeptides and polynucleotides. The invention further relates to procedures for producing the enzyme polypeptides and polynucleotides. Biotin is an essential co-factor for a major class of enzymes that are involved in lipid, amino acid, and carbohydrate metabolism (Moss et al. (1971) Adv. Enzymol. 35:321-422; Wood et al. (1977) Annu. Rev. Biochem. 46:385-413; Wood et al. (1985) Ann. N Y Acad. Sci. 447:1-22; Knowles (1989) Annu. Rev. Biochem. 58:195-221). The biotin-requiring enzymes (BREs) of aerobic organisms are either carboxylases or transcarboxylases. The carboxylases catalyze the transfer of a carboxyl group from bicarbonate to a metabolite such as pyruvate, propionyl-CoA, acetyl-CoA, or 3-methylcrotonyl-CoA. In a first step the biotin co-factor
9
This has been a common practice outside the United States prior to December 2000.
Patents 161
is carboxylated in a reaction that requires ATP, Mg.sup.2+, and bicarbonate. The carboxyl group is then subsequently transferred from the carboxybiotin intermediate to the metabolite that is specific for each BRE. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Arrays using polymerized monomolecular films and methods for using and manufacturing the same Inventor(s): Bednarski, Mark D.; (Los Altos, CA), Guccione, Samira; (Hillsborough, CA), Hobbs, Susan K.; (Fremont, CA), Shi, Gongyi; (Dublin, CA), Yang, Yi-Shan; (Saratoga, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030104451 Date filed: October 31, 2002 Abstract: Devices and methods of use and manufacture for the identification and characterization of analytes, e.g. proteins, are provided. The subject devices are characterized by having a substrate with a polymerized monomolecular film over at least a portion of the substrate, the monomolecular film having at least one ligand or specific binding pair member associated therewith. Preferably the monomolecular film is stable to the laser intensities employed in MALDI-MS. In certain embodiments, the ligands are biotin, integrin antagonists, antibodies and antigens. In using the subject devices, a subject device is contacted with a sample. If present in the sample, a member of the binding pair of interest binds to its complementary ligand and, once bound, can be analyze by mass spectroscopy techniques. Also provided are kits, which include the subject devices. Excerpt(s): A current emphasis in proteomics is the development of materials for use in immobilized microarrays for protein detection similar to that of gene expression analysis. Currently, materials for microarray development have focused on arraying biomolecules in a manner that retains their biological activity. Antibodies, small molecules, peptide ligands, purified recombinant proteins, and whole tissue preparations have been non-specifically arrayed on different materials. A more difficult problem is to design materials that can capture specific proteins and limit nonspecific binding to the surface. So far, the investigation of small molecule or peptide arrays have been limited to model systems that contain only purified proteins binding to their respective ligands displayed on the material surface. In addition, the captured biomolecule is often present at low concentrations and must be accurately detected and quantified. No materials have demonstrated the capability to both reproducibly capture specific proteins from complex protein mixtures and be amenable for rapid mass spectral analysis. For example, one current approach to protein identification involves isolating protein using two dimensional polyacrylamide gel electrophoresis (2D-PAGE) followed by enzyme degradation of the isolated protein spots on the gel and the preparation of peptide maps and bioinformatic searches. To perform 2D-PAGE, at least hundreds of femtomoles to low picomoles of isolated protein must be present on a single gel spot in order to identify the protein and/or characterize it. Thus, significant drawbacks to 2D-PAGE include, but are not limited to, time consuming processes, large sample requirements, time consuming sample preparation, low protein solubilization, separation of low abundance proteins from complex mixtures difficulties, high sample loads needed to evaluate co-translational and post-translational modifications and
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difficulties when used with highly basic proteins and very large (greater than 150 kDa) or very small (less than 10 kDa) proteins. In addition to 2D-PAGE, methods such as 2Dliquid chromatography and capillary zone electrophoresis have been employed. However, these also suffer from similar problems, i.e., lengthy processes, etc. Recently, chemical modification of surfaces by organic molecules or films has been successfully used to identify and/or characterize analytes such a proteins in a sample. Such chemically modified surfaces are commonly known as arrays (also known as microarrays). These arrays, in which a plurality of ligands or members of a specific binding pair are deposited onto a solid support surface in the form of an "array" or pattern, find use in a variety of applications, including, but not limited to, proteomic identification and analysis, gene expression analysis, drug screening, nucleic acid sequencing, mutation analysis, and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biotin derivatives Inventor(s): Nilsson, Rune; (Lund, SE), Sandberg, Bengt E.B.; (Hjarup, SE), Wilbur, D. Scott; (Edmonds, WA) Correspondence: Smith, Gambrell & Russell, Llp; Attorneys AT Law; Suite 800; 1850 M Street, N.W.; Washington; DC; 20036; US Patent Application Number: 20020159994 Date filed: June 15, 2001 Abstract: A method for the conditioning of an extracorporeal device is described, as well as a method for extracorporeal extraction of toxic material from mammalian body fluids in connection with diagnosis or treatment of a mammalian condition or disease, in which methods reagents having the ability to extract toxic material from mammalian body fluids are involved, and an extracorporeal device comprising said reagent. Excerpt(s): The present invention refers to a method for the conditioning of an extracorporeal device and to a method for extracorporeal extraction of toxic material from mammalian body fluids in connection with diagnosis or treatment of a mammalian condition or disease, in which methods reagents having the ability to extract toxic material from mammalian body fluids are involved, and to an extracorporeal device comprising said reagent. Toxic materials may be introduced into the blood of humans by accidents, from disease states, from bacterial or viral infections, or from administration of substances for treatment of certain diseases (e.g. cancer therapy). Many of these toxic materials may do considerable damage to body tissues such as kidney, liver, lung and bone marrow, and may even be fatal. It is desirable to remove such materials from the blood as quickly as possible. Although the body has natural defense mechanisms to remove unwanted toxic materials, those methods can be ineffective in many examples. Thus, certain toxic materials are best removed from the blood in an extracorporeal device. An example of such a device is the kidney dialysis machine, where toxic materials build up in the blood due to a lack of kidney function. Other medical applications where an extracorporeal device can be used include: [1] removal of radioactive materials, [2] removal of toxic levels of metals, [3] removal of toxins produced from bacteria or viruses, [4] removal of toxic levels of drugs, and [5] removal of whole cells (e.g. cancerous cells, specific hematopoietic cells--e.g. B, T, or NK cells) or removal of bacteria and viruses. In order for the extracorporeal device to function in toxin removal, it must have a chemical entity bound on it that has a high binding affinity with the toxic material that is to be removed from blood. Rather than
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binding that chemical entity directly to the column matrix in the extracorporeal device, it is preferentially bound through another binding pair of molecules. This arrangement of binding is used to make the toxin binding moiety more available in the blood and to make the device more generally applicable to a variety of toxic materials. A column matrix material is used that provides a high surface area while not restricting the flow of blood through it (Nilson, R. et. al. EPC 567 514). The column matrix has a protein (avidin or streptavidin) bound to it that has a high affinity for another molecule (e.g. biotin). That column is conditioned for use in a particular medical application by conjugation of a moiety that has a high affinity for the toxic material with two molecules of biotin such that attachment to the column matrix can be readily achieved. This conditioning reagent contains two biotin moieties rather than one as this configuration provides a higher degree of stability to the column matrix. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biotin-peg-substrate for a lipase assay Inventor(s): Fowler, Anne; (Forest Farm Estate, GB), Hawes, Calvin Richard; (Forest Farm Estate, GB), James, David Martin; (Forest Farm Estate, GB), Poulsen, Fritz; (Bagsvaerd, DK), Price-Jones, Molly Jean; (Forest Farm Estate, GB), Tornqvist, Hans; (Bagsvaerd, DK) Correspondence: Amersham Biosciences; Patent Department; 800 Centennial Avenue; Piscataway; NJ; 08855; US Patent Application Number: 20040014133 Date filed: December 9, 2002 Abstract: Disclosed is a compound of Formula (I), wherein: L is a linking agent; B is a binding agent; X is an atom or group suitable for attaching L to the glycerol chain; and R is a straight chain saturated or unsaturated alkyl group having from 8 to 30 carbon atoms, substituted with M' or M" wherein at least one of M' and/or M" is a detectable label. The compound can be used as a lipase substrate in a solid phase-based assay system, such as a scintillation proximity assay, to detect lipase enzyme activity. Excerpt(s): The present invention describes a novel substrate for use in an assay for lipase enzyme activity. In particular, this novel substrate can be labelled and used in a homogeneous assay. Lipases are enzymes that catalyse the hydrolysis of triacylglycerols in the first step in recovering stored fatty acids for energy production. The sequence of hydrolysis from the three positions on glycerol depends on the specificity of the particular lipase involved. Lipase enzyme activity is an important function and its strict regulation is necessary to ensure healthy metabolism. For example, lipases in adipose tissue are key enzymes for the release of major energy stores. Their activity is under hormonal control to ensure that triacylglycerol hydrolysis is balanced with the process of triacyglycerol synthesis to assure adequate energy stores and yet avoid levels of fatty acids becoming so high as to cause adverse effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Biotinylation of proteins Inventor(s): Zhang, Lin; (O'Fallon, MO) Correspondence: Donald R. Holland; Harness, Dickey & Pierce, P.L.C.; 7700 Bonhomme, Suite 400; Clayton; MO; 63105; US Patent Application Number: 20040033603 Date filed: August 19, 2002 Abstract: A eukaryotic bicistronic expression system for in vivo biotinylation of a protein is disclosed. The bicistronic expression system is based upon a polynucleotide which comprises a nucleic acid encoding a fusion protein made up of a selected protein and a biotinylation peptide, a nucleic acid sequence coding for an internal ribosome entry site and a nucleic acid sequence encoding a biotin ligase. Also disclosed are vectors and host cells containing the nucleic acid as well as methods for preparing a biotinylation protein and kits comprising the nucleic acid. Excerpt(s): This invention relates generally to the biotinylation of proteins, and, more particularly, to nucleic acid molecules, vectors and cells which can be used to produce biotinylated fusion proteins. Modem biochemistry and cell biology depend heavily on the ability to covalently attach affinity tags to biomolecules such as proteins. An affinity tag, when used with a binding partner for the affinity tag, provides an aid to detection or isolation of a biomolecule. One of the most commonly used affinity tags is the biotin moiety. Biotin, a naturally occurring vitamin, has several high-affinity binding partners, such as avidin, streptavidin, monomeric avidin, and anti-biotin antibodies (both polyclonal and monoclonal). The binding between biotin and avidin is among the strongest non-covalently attachments between molecules known, having a K.sub.d of approximately 10.sup.-15 (Wilchek, M., and Bayer, E. A. (1988). The avidin-biotin complex in bioanalytical applications. Anal. Biochem. 171: 1-32). Because of this unusually high binding affinity, and because biotinylation of a biomolecule can often be accomplished without altering the protein's activity, biotinylation is one of the most important tools available for tagging proteins. For example, streptavidin immobilized on a solid support can be used to separate a biotin-tagged protein from a mixture: the biotinylated protein attaches to the immobilized streptavidin, and the mixture can be washed away, leaving the biotinylated protein attached to the solid support. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cell-based assay for detecting activation of poly (ADP-ribose) polymerase Inventor(s): Szabo, Csaba; (Gloucester, MA), Virag, Laszlo; (Lugossy, HU) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20020164633 Date filed: April 18, 2002 Abstract: The present invention relates to methods of detecting poly(ADP-ribose) polymerase ("PARP") activity in cells and tissue by contacting a cell with an effective amount of biotinylated NAD.sup.+ and detecting the presence of incorporated biotin within the cell. The invention also relates to the identification oxidatively stressed tissues and cells by detecting PARP activity. The invention also relates to identifying a patient suffering from a disorder that causes PARP overexpression.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/285,175 filed Apr. 20, 2001, which is incorporated herein by reference in its entirety. Poly(ADP-ribose) polymerase ("PARP") is a nuclear enzyme that becomes activated in response to DNA damage (de Murcia & Menissier de Murcia, 1994, Trends Biochem Sci 19:172-176). Activated PARP cleaves NAD to nicotinamide and ADP-ribose, and polymerizes the latter on to nuclear acceptor proteins such as histones, transcription factors and PARP itself. Poly-ADP ribosylation contributes to DNA repair and to the maintenance of genomic stability (Wang et al., 1997, Genes Dev 11:2347-58; SimbulanRosenthal et al., 1999, Simbulan-Rosenthal et al 1999, Proc. Natl. Acad. Sci. U.S.A. 96:13191-13196; and Muiras & Burkle, 2000, Exp. Gerontol. 35:703-709). During inflammation, ischemia-reperfusion or shock, free radical/oxidant-induced DNA single strand breakage triggers the over-activation of PARP, which leads to depletion of NAD (Szabo & Dawson 1998, Trends Pharmacol. Sci. 19:287-298 and Szab, 2000, Cell Death: the Role of PARP. Boca Raton, Fla., CRC Press). In an effort to re-synthesize NAD+, ATP will also be consumed, resulting in necrotic type cell death (Schraufstatter et al., 1986, Proc. Natl. Acad. Sci. U.S.A. 83:4908-4912; Virag et al., 1998, Immunology 94:345-355 and Virag et al., 1998, J. Immunol. 161:3753-3759). This PARP mediated suicidal pathway has been implicated in the cell death of immune stimulated macrophages, as well as in peroxynitrite- or hydrogen peroxide-induced dysfunction or cell death of thymocytes, macrophages, endothelial cells, neuronal cells and fibroblasts (Soriano et al., 2001, Nat Med 7:108-13; Virag et al., 1998, Immunology 94:345-355; Szabet al., 1998, Proc Natl Acad Sci U.S.A. 95:3867-3872; and Zingarelli et al., 1996, J. Immunol. 156:350-358). Inhibition of PARP activity by pharmacological inhibitors or the absence of functional PARP enzyme in PARP knock out animals provides significant protection in animal models of a wide variety of diseases including various forms of inflammation, shock, stroke, myocardial ischemia, diabetes and diabetic endothelial dysfunction (Szabo & Dawson 1998, Trends Pharmacol. Sci. 19:287-298 and Szab, 2000, Cell Death: the Role of PARP. Boca Raton, Fla., CRC Press). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Chromium/biotin treatment of dyslipidemia and diet-induced post prandial hyperglycemia Inventor(s): Greenberg, Danielle; (Waccabuc, NY), Harpe, Jon De La; (New York, NY), Juturu, Vijaya; (Dobbs Ferry, NY), Komorowski, James R.; (Trumbull, CT) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020197331 Date filed: February 27, 2002 Abstract: A method for treating dyslipidemia and/or post prandial hyperglycemia by administering a combination of a chromium complex and biotin to an individual in need thereof is disclosed. The two compounds are administered orally or parenterally in daily dosages which provide between 25.mu.g and 1,000.mu.g of chromium and between 25.mu.g and 20 mg biotin. A method for reducing the glycemic index of food is similarly provided. Excerpt(s): The present application claims priority to Provisional Application 60/271,881 entitled CHROMIUM/BIOTIN TREATMENT HYPERCHOLESTEROLEMIA, filed on Feb. 27, 2001. The subject matter of aforementioned application is hereby incorporated by reference in its entirety.
No. OF the The
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present invention relates to the improvement of blood cholesterol and triglyceride levels. More specifically, the invention relates to methods of lowering LDL cholesterol, increasing HDL cholesterol, and decreasing triglyceride levels in the blood by administering doses of chromic picolinate and biotin. Additionally, the present invention relates to methods and compositions for reducing post prandial hyperglycemia and for lowering the glycemic index of foods. Dyslipidemias are disorders of lipoprotein metabolism, including lipoprotein overproduction or deficiency. These disorders may be manifested by elevation of the serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride concentrations, and a decrease in the high-density lipoprotein (HDL) cholesterol concentration. Each year, millions of human beings suffer from the sequelae of hypercholesterolemia. Examples of the afflictions include hypertension, coronary artery disease, congestive heart failure, peripheral vascular disease, aneurysms, and death due at least in part to these conditions. Elevated blood cholesterol is one of the major modifiable risk factors for coronary heart disease (CHD), the leading cause of death in the United States. Kannel, W. B. et al. Declining Cardiovascular Mortality. Circulation 70:331-336 (1984). CHD is responsible for roughly 490,000 deaths each year. National Center for Health Statistics. Annual summary of births, marriages, divorces, and deaths: United States, 1993. Monthly vital statistics report; vol 42 no 13. Public Health Service, 1994. Nonfatal myocardial infarction (MI) and angina are similarly a source of substantial morbidity. Secondary physiological effects of hypercholesterolemia include cerebral strokes, compromised liver function, renal artery blockage, senility, male impotence, and arteriosclerotic aneurysms. The risk of such diseases can be reduced by increasing the level of HDL cholesterol in the blood and/or decreasing the level of LDL cholesterol in the blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Colorimetric in situ hybridization detection methods Inventor(s): Fletcher, Jonathan; (Brookline, MA), Xiao, Sheng; (Boston, MA) Correspondence: Helen C. Lockhart; Wolf, Greenfield & Sacks, P.C.; Federal Reserve Plaza; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20030044822 Date filed: April 26, 2002 Abstract: The invention is a method for genomic subtractive hybridization. Specific nucleic acid sequences are removed from a sample of nucleic acid sequences by specifically hybridizing the sequences to a complementary nucleic acid sequence bound to a target molecule such as biotin. The target molecule is then contacted with a binding partner such as avidin and separated from the sample of nucleic acid sequences. As the target is separated from the sample the hybridized nucleic acid sequences are also removed from the sample. The method preferably involves the removal of repetitive nucleic acid sequences from a nucleic acid sample to generate a library of probes that are substantially free of repetitive nucleic acid sequences. Excerpt(s): The present invention relates to a method for genomic subtractive hybridization. The invention also relates to methods for generating probes for in situ hybridization techniques. In particular, the methods for genomic hybridization are useful for generating probes for techniques such as in situ hybridization. Chromosomes within a living cell encompass all of the DNA of a particular organism. The number and structure of chromosomes within a cell are indicative of various normal and abnormal
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developmental traits. For instance, the presence of a particular chromosome type or number of a particular chromosome may be indicative of an abnormal condition. Humans having three copies of chromosome 18 (trisomy) develop a fatal disorder causing death within one year of birth and subjects having three copies of chromosome 21 (trisomy 21) develop Downs syndrome. In general chromosome abnormalities can result from extra or missing individual chromosomes, extra or missing portions of a chromosome, or chromosomal rearrangements, including translocations, deletions, and inversions. The trisomies discussed above involve addition of chromosomal material. A translocation involves the transfer of a piece of a chromosome to another chromosome. An example of a disorder involving an exchange of chromosomal material is chronic myelogenous leukemia which involves a translocation of chromosomal material from chromosome 9 to chromosome 22. An inversion involves a reversal in polarity of a chromosomal segment. Dicentrics produce a chromosome with two centromeres. Characteristic chromosome abberations have been described in a wide range of tumors. Specific oncogene and tumor suppressor gene targets affected by these chromosomal abnormalties have been characterized in some tumors but most of them remain to be studied. A major goal in studying human cancer chromosome and gene aberrations is to elucidate biological pathways responsible for neoplastic transformation. Several such pathways have already been identified through characterization of particular cancer chromosome aberrations (1, 3). Another goal in cancer chromosome evaluation is the identification and validation of novel diagnostic and prognostic markers (4, 5). Cytogenetic markers have utility as histological adjuncts, and methods that delineate diagnostic chromosomal aberrations or associated molecular changes are becoming increasingly important in experimental pathology (6-8). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for prophylactic and therapeutic supplementation of nutrition in subjects Inventor(s): Balzer, Charles; (Lavalette, NJ), Giordano, John A.; (West Orange, NJ) Correspondence: Mckenna & Cuneo, Llp; 1900 K Street, NW; Washington; DC; 20006; US Patent Application Number: 20030012826 Date filed: October 19, 2001 Abstract: The present invention relates to compositions without added iron and methods for prophylactic nutritional supplementation and therapeutic nutritional supplementation. Specifically, the method involves administering to an individual a composition comprising carotenoids, vitamin E, vitamin D, vitamin C, thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin, pantothenic acid, cobalamin, magnesium, manganese, zinc, selenium, chromium, copper, alpha lipoic acid, and lutein, wherein the composition is free of added iron. Excerpt(s): The present invention is related to and, in accordance with the provisions of 35 U.S.C.sctn.119(e), claims the benefit of provisional patent application Serial No. 60/301,443 filed Jun. 29, 2001, which is expressly incorporated fully herein by reference. The present invention relates to compositions comprising various vitamins and minerals, and without added iron, and methods for using these compositions for prophylactic nutritional supplementation and therapeutic nutritional supplementation in, for example, physiologically stressful conditions and to minimize the effect of exogenous iron supplementation. Nutrition plays a critical role in maintaining good
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health. Proper nutrition prevents dietary deficiencies, and also protects against the development of disease. Proper nutrition plays an increasingly important role as the body faces physiological stress. For example, as the body ages it suffers significant physiological stresses. Specifically, as the body metabolism shifts to accumulating larger fat stores and decreasing lean body mass, this increase in body weight may lead to obesity and associated conditions such as diabetes, cardiovascular disease, hypertension, osteoarthritis, and cancer. Other conditions, such as anorexia, malnutrition, gastrointestinal disorders, chronic alcoholism, chronic infections, acute infections, congestive heart failure, hyperthyroidism, poorly controlled diabetes, cheilosis, gingivitis, stomatitis and dietary restrictions, often result in physiological stresses that may be exacerbated by poor nutrition. In particular, these disease states may result in increased oxidative stress or elevated homocysteine levels that further compromise health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Device and method for integrated diagnostics with multiple independent flow paths Inventor(s): Barski, Stanislaw JR.; (Limerick, ME), Clark, Scott M.; (Cape Elizabeth, ME), Kepron, Michael R.; (Standish, ME), Suva, Robert H.; (Windham, ME), Workman, Erwin F. JR.; (Cape Elizabeth, ME) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030040021 Date filed: April 3, 2002 Abstract: Devices and methods for performing assays to determine the presence or quantity of a specific analyte of interest in a fluid sample. In devices according to this invention two separate flow paths are established sequentially in the device with a single user activation step. The first flow path delivers the analyte of interest (if present in the sample) and conjugate soluble binding reagents to the solid phase. If analyte is present, an analyte:conjugate complex is formed and immobilized. The volume of sample delivered by this first path is determined by the absorbent capacity of the solid phase, and not by the amount of sample added to the device, relieving the user from the necessity of measuring the sample. The sample/conjugate mixture is prevented from entering the second flow path because the capillarity and the surface energy of the second flow path prevent it from being wetted by this mixture. The second flow path allows a wash reagent to remove unbound conjugate and sample from the solid phase to the absorbant, and optionally to deliver detection reagents.The invention may be adapted to many assay formats including, sandwich immunoassays, colloidal gold, or sol particle assays, heterogeneous generic capture assays and competitive assays.In one embodiment, sandwich assays can be performed by immobilizing an analyte binding reagent on the solid phase, and drying a labeled analyte binding reagent in the first flow path. In a competitive assay embodiment, the first flow path would contain labeled analyte that is dissolved by the sample, and the analyte binding reagent is immobilized on the solid phase. In each of these embodiments, the assay can be further modified to run in a "generic capture" format, where the solid phase binding reagent is instead conjugated to a generic ligand such as biotin, and dried in the first flow path (either together or separately from the other assay reagents), and a generic ligand binding reagent (such as avidin) is immobilized on the solid phase.Another aspect of the present invention includes a subassembly for the immunoassay device that is comprised of a
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plastic housing and a means for delivering fluid and/or wash solution. This subassembly comprises a structure formed from a hydrophobic polymer selectively treated with a water insoluble surface active agent that has been applied as a solution in an organic solvent rendering portions of the surface hydrophilic. When the surface is contacted with an aqueous liquid, it flows only along the treated areas, creating a defined fluid flow path, thereby delivering sample/conjugate solutions to said solid phase. Excerpt(s): This invention relates to devices and methods for performing assays to determine the presence or quantity of a specific analyte of interest in a fluid sample. Devices of this invention assay a measured amount of sample employing at least two separate and distinct flow paths which are initiated simultaneously with a single user activation step. These paths are timed for the sequential delivery of assay reagents to the reaction zone, followed by wash or substrate and wash reagents to that zone. These inventive devices and methods may be used for qualitative, semi-quantitative and quantitative determinations of one or multiple analytes in a single test format. They may be practiced with ELISA, sol particle and other assay formats, and are particularly suitable for simultaneous multiple analyte assays. These inventive devices and methods provide for the controlled, self delivery of reagents with no timed steps, and minimal user intervention, in most instances a single activation step. Many prior art assay devices and systems require the user to measure or control the amount of sample added to the device, for example, by dilution. Many prior art assays and systems also require the user to perform a timed sequence of steps and/or to make multiple physical interventions to the device in order to perform the assay. Buechler et al., U.S. Pat. Nos. 5,458,852 and 5,885,527 (1995 and 1999, respectively), disclose diagnostic devices which do not use porous membranes. In assay methods using such devices, fluid flow is unidirectional and reaction and detection occur in distinct zones. Excess sample/conjugate mixture is used to wash the detection zone. The use of a separate, non-sample wash is not taught or suggested, limiting the versatility of assays of this invention. Likewise, Buechler does not teach or suggest the creation of a second flow path. The time gate in Buechler functions as a delay mechanism in a fluid path, not to redirect fluid flow or to permit different fluids to flow sequentially through a reaction zone. The methods and devices of Buechler et al. do not allow one to use multiple reagents, different wash and substrate reagents and cannot be used in an enzyme amplified assay. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Devices and methods for isolating and recovering target cells Inventor(s): Bernstein, Steve; (Los Olivos, CA), Ross, Amelia A.; (Laguna Niguel, CA) Correspondence: Oppenheimer Wolff & Donnelly Llp; 840 Newport Center Drive; Suite 700; Newport Beach; CA; 92660; US Patent Application Number: 20030175818 Date filed: September 18, 2002 Abstract: A cell isolating device and method is provided to concentrate or isolate cells with specific characteristics from a mixture of different cell types. One embodiment may comprise two subtypes of antibodies that are directly conjugated to biotin (Ab.sub.b) and conjugated to a fluorescent molecule (Ab.sub.f). The conjugated antibodies (Ab.sub.b+Ab.sub.f) bind to the target cells in a mixed cell suspension. The cell suspension is then passed over an immobilized avidin or streptavidin substrate on a
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glass microscope slide. The biotinylated target cells adhere to the avidin/streptavidin substrate, while the unbound cells are washed off and collected in a wicking member. Captured cells on the avidin/streptavidin substrate may then be visualized directly using a fluorescent microscope or detected and enumerated via an on-board fluorescent detection device. Additional chemicals and/or physical manipulation may then be applied to the device to release viable target cells for subsequent analysis. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/364,679, filed Mar. 15, 2002, and whose entire contents are hereby incorporated by reference. All living bodies are comprised of individual cells, each cell defining an environment where various biological and chemical reactions take place. In particular, each cell contains a cell membrane that separates the internal environment of the cell from the external environment and thereby controls the entry and exit of various nutrients and waste. Additionally, the cell membrane includes various proteins, sugars, and other molecules that "identify" a particular cell type, these identifying molecules commonly being referred to as antigens. In order to better understand the function and pathologies of cells, numerous methods have been developed to isolate and concentrate a desired target cell population from a mixed cell population so that the target cell population can be further analyzed. One such method is based upon cell density wherein a mixture of cells is spun at high speeds in a centrifuge so that the higher density cells become separated for the lesser density cells. Although this method is effective at separating different cells, centrifugation does not have good cell-separation specificity as different types of cells may have the same or similar cell density. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Diagnosis kit for mycobacterium species indentification and drug-resistance detection and manufacturing method thereof Inventor(s): Kim, Hyung-Jung; (Gyonggi-do, KR), Kim, Jeong Mi; (Seoul, KR), Kim, Na Young; (Seoul, KR), Park, Mi Sun; (Busan, KR), Yoon, Sung Wook; (Seoul, KR) Correspondence: Frank Chau; F Chau & Associates; Suite 501; 1900 Hempstead Turnpike; East Meadow; NY; 11554; US Patent Application Number: 20040038233 Date filed: July 7, 2003 Abstract: The present invention relates to diagnosis kit for Mycobacterium species identification and drug-resistance detection and manufacturing method thereof, which can discriminate a Mycobacterium Tuberculosis rpoB gene point mutation relating to the Mycobacterium species identification and drug-resistance swiftly, exactly and in large quantities using an oligonucleotide chip. The diagnosis kit for Mycobacterium species identification and drug-resistance detection in accordance with the present invention consists of an oligonucleotide chip including a Mycobacterium tuberculosis complex probe, a Mycobacterium species identification probe and a drug-resistance detection probe of a Mycobacterium tuberculosis rpoB gene, and a fluorescent material containing a biotin-binding protein so as to detect hybridization of amplified products of a specimen marked as biotine and the corresponding probe. Excerpt(s): The present invention relates to a diagnosis kit for Mycobacterium species identification and drug-resistance detection and a manufacturing method thereof, and more specifically, to a diagnosis kit for Mycobacterium species identification and drugresistance detection in which point mutations of Mycobacterial rpoB gene related to the
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drug-resistance can be discriminated speedily and accurately in large quantity by using an oligonucleotide chip, and a manufacturing method thereof. About two million people die from tuberculosis worldwide each year. The increase in immigration, the spread of HIV/AIDS, and the emergence of drug-resistance strains are enhancing the mortality of tuberculosis. AIDS patients and newborns with weak immune system can develop tuberculosis from not only Mycobacterium tuberculosis infection but also MOTT (Mycobacterium other than tuberculosis) infection, particularly, Mycobacterium aviumintracellulare (MAI), Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasaii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium scrofulaceum, and Mycobacterium szulgai. Tuberculosis is normally treated by chemotherapy with various anti-tuberculosis drugs. Since there are numerous different strains of Mycobacteria with diverse drug-susceptibility, detection and identification of the causative bacterium is important for the effective treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Dioxin derivatives and method of measurement therewith Inventor(s): Kodaira, Tsukasa; (Tokushima, JP), Yanaihara, Noboru; (Toyonaka-shi, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030108955 Date filed: November 1, 2002 Abstract: The invention provides a highly sensitive measurement and detection technique for dioxins, which has advantages inherent to immunoassay; and markers to be used in the technique.Disclosed are a biotinylated dioxin derivative of formula (1): 1(wherein X represents a hydrogen atom or a chlorine atom; R.sup.1 represents a biotin residue; R.sup.2's, which may be identical to or different from one another, independently and individually represent an arginine residue or a lysine residue; n is an integer from 1 to 5 inclusive; and m is an integer from 1 to 3 inclusive), and an immunoassay method for dioxins characterized by using the derivatives as a marker. Excerpt(s): The present invention relates to a novel biotinylated dioxin derivative, and to an improved immunoassay method for dioxins, inter alia, 2,3,7,8-tetrachlorodibenzo-pdioxin (hereinafter referred to as "2,3,7,8-TCDD"), making use of the derivative. Dioxins collectively refer to polychlorinated dibenzo-p-dioxins (PCDDs) and their analogues, polychlorinated dibenzofurans (PCDFs). Dioxins include numerous isomers which differ from one another in terms of the positions and numbers of chlorine atoms. Dioxins are discharged from factories and incinerators when, for example, chlorinecontaining organic compounds are incinerated, and spread into the air, rivers, and soil. Dioxins have attracted attention because of their toxicity; in particular, 2,3,7,8-TCDD is highly toxic, adversely affecting organs and physiological functions of humans, livestock, and poultry, and raising serious social problems in both Japan and overseas countries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Directed enzymatic modification of analytes for affinity capture and analysis Inventor(s): Schulman, Howard; (Palo Alto, CA) Correspondence: Swanson & Bratschun L.L.C.; 1745 Shea Center Drive; Suite 330; Highlands Ranch; CO; 80129; US Patent Application Number: 20030003512 Date filed: June 27, 2002 Abstract: Proteins are selectively extracted from complex biological mixtures for subsequent analysis by methods such as mass spectrometry. Protein-binding (e.g., PDZ or SH2) or cellular compartmentalizing (e.g., membrane-targeting) domains are provided to target specific proteins, and targeted proteins are enzymatically modified by attachment of modification molecules. For example, targeted proteins can be biotinylated by the enzyme biotin protein ligase. The protein-targeting domain and protein-modifying enzyme can be immobilized on a solid surface (macroscopic planar surface or particle surface), provided as a fusion protein, or chemically coupled. The modified proteins are then exposed to complementary molecules (e.g., avidin or streptavidin) that bind strongly to the modification molecule, resulting in affinity capture of the selected proteins. Because the protein-targeting domain brings the protein in proximity to the active site of the enzyme, the method effectively broadens the substrate specificity of the enzyme, allowing affinity capture of any desired protein subset. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/301,683, "Targeted Biotinylation for Affinity Capture in Multiplexed and Quantitative Mass Spectrometry of Analytes," filed Jun. 27, 2001, incorporated herein by reference. The present invention relates generally to qualitative and quantitative analysis of components of biological mixtures. More particularly, it relates to a method for selectively enzymatically modifying subsets of proteins in a mixture to enable their subsequent affinity capture and analysis by methods such as mass spectrometry. Recent developments in electrospray ionization (ESI) mass spectrometry (MS) and matrixassisted laser desorption ionization (MALDI) MS enable the quantification and structural elucidation of novel proteins in complex biological samples. Although MS can be used for multiplexed quantitative assays over a broad range in molecular weight, interpreting mass spectra becomes difficult when the samples contain a large number of components of similar mass. Furthermore, the wide concentration range of proteins in biological samples makes it difficult to detect low-abundance proteins, because highabundance proteins overwhelm or saturate separation systems. These problems can be addressed by separating the sample in a manner that reduces the complexity of the proteome and simplifies the acquired mass spectra. One useful sample separation method is affinity capture, in which proteins are selectively extracted from solution onto a surface containing molecules with which the proteins interact. The surface can be a single surface (e.g., planar) to which the sample is applied or the surfaces of nano- or microparticles dispersed in the sample and recovered after capture. The captured proteins subsequently can be eluted from the surface (if necessary) for analysis by MS. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Enhancement of intracellular delivery and tissue targeting of drugs and genes Inventor(s): Albelda, Steven M.; (Bala Cynwyd, PA), Muzykantov, Vladimir R.; (Warwick, PA) Correspondence: Licata & Tyrrell P.C.; 66 East Main Street; Marlton; NJ; 08053; US Patent Application Number: 20030206911 Date filed: May 28, 2003 Abstract: A method for enhancing intracellular delivery of effector molecules is provided. The method involves modifying selected antibodies with biotin and streptavidin, conjugating these antibodies with an effector molecule, and delivering the conjugated effector to an intracellular target specifically recognized by the antibody. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/623,822 filed Oct. 25, 2000, which claims the benefit of priority from PCT Application Serial No. PCT/US99/05279 filed Mar. 10, 1999 and U.S. Provisional Application Serial No. 60/077,375 filed Mar. 10, 1998 each of which are herein incorporated by reference in their entirety. Targeting of drugs or genetic material to defined cells, tissues or organs increases the specificity and effectiveness of drug therapy and reduces the incidence of potentially harmful side effects. Intracellular delivery and proper intracellular processing are required for specific and effective therapeutic applications of certain classes of drugs including, but not limited to, immunotoxins, antioxidants, NO-donors, antibiotics, antisense oligonucleotides, nucleic acids and intracellular hormones. Further, intracellular delivery of gene therapy products is crucial to successful treatment. In the case of antioxidants, immunotoxins, antisense agents, hormones, gene therapy agents and other therapeutic compounds, referred to herein as "effectors", only limited spontaneous cellular internalization typically occurs. Accordingly, strategies to facilitate or enhance internalization have been developed and include chemical modification with polyethylene glycol (Abuchowski et al. J. Biol. Chem. 1977 252(11):3852-3586; Abuchowski et al. J. Biol. Chem. 1992 252(11):3578-3581; Beckman et al. J. Biol. Chem. 1988 263:6884-6892), encapsulation in liposomes (Freeman et al. J. Biol. Chem. 1983 258:12534-12542; Briscoe et al. Am. J. Physiol. 1995 12(3):L374-L380), and conjugation with ligands of internalizable receptors (Wagner et al. Adv. Drug. Del. Rev. 1994 14:113-135; Chen et al. FEBS Lett. 1994 338:167-169). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Finely particulate functional metal and finely particulate functional semiconductor each with dispersion stability and process for producing the same Inventor(s): Ishii, Takehiko; (Washinomiya-Mati, JP), Kataoka, Kazunori; (Nakano-ku, JP), Nagasaki, Yukio; (Moriya-mati, JP), Otsuka, Hidenori; (Kawasaki-shi, JP) Correspondence: Sherman & Shalloway; 413 N Washington Street; Alexandria; VA; 22314; US Patent Application Number: 20040038506 Date filed: February 28, 2003 Abstract: A stabilized dispersion of metal fine particles comprising, fine particles of metal which is obtained by reducing at least one metallic acid or salt thereof selected from the group consisting of haloauric acid, haloplatinic acid, silver nitrate and halorhodic acid by a reducing agent in the aqueous solution of (1) R-PEG-SX [R is a
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functional group selected from the group consisting of acetal, aldehyde, hydroxyl group, amino group, carboxyl group, active ester group, azide group, biotin group, monosaccharide, oligosaccharide, amino acid, nucleic acid, allyl group, vinyl benzyl group, methacryloyl group and acryloyl group, PEG is --(CH.sub.2CH.sub.2O).sub.n--, X is H or pyridylthio group] or (2) R-PEG/PAMA (given structural formula A), and said fine particles load a polymer having PEG unit possessing above mentioned functional group on the surface. Excerpt(s): The present invention relates to a stabilized dispersion of metal fine particles having high functional group at the voluntarily end of a compound having a PEG unit mentioned below, block copolymer having said PEG unit and unit of structural formula A or graft polymer of structural formula B, obtained by existing a compound having a PEG unit which possesses a functional group disclosed in claim 1, a compound having a PEG unit which possesses a functional group disclosed in claim 3 and block polymer of structural formula A or graft polymer of structural formula B having a PEG unit which possesses a functional group disclosed in claim 5 during the producing process of monodispersed metal or semiconductor fine particles (colloidal particles), further relates to the method for production of said stabilized dispersion of metal fine particles. In general, metal or semiconductor colloid (ultra fine particle) is an important industrial material which is broadly used in various fields, for example, medical treatment [as a medicine (medicine of ultra fine particles having penetrating ability to membrane internus), various inspection agents or DDS], dye (coating), foods or catalyst. Especially, metal particles of several tens to several hundreds nano meter size (called as submicron: meso size) and having narrow distribution is expected as a high functional materials such as diagnostic which uses Raman spectrum or microwave or a labeling agent for electron microscope. For example, Assay method, which uses colloidal metal particles has been developed. Said method is characterized as follows. That is, since colloidal metal is used as a label, the specific bonding site to be labeled is bonded on colloidal metal by absorption and said labeling material is detected and measured (JP Laid Open Publication 6-116602, hereinafter shortened to Document A). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Forming and modifying dielectrically-engineered microparticles Inventor(s): Becker, Frederick F.; (Houston, TX), Gascoyne, Peter R.C.; (Bellaire, TX), Sharma, Susan; (Sugarland, TX), Vykoukal, Daynene; (Houston, TX), Vykoukal, Jody; (Houston, TX) Correspondence: Michael C. Barrett; Fulbright & Jaworski L.L.P.; 600 Congress Avenue, Suite 2400; Austin; TX; 78701; US Patent Application Number: 20030119057 Date filed: December 20, 2001 Abstract: Engineered microparticles, libraries of microparticles, and methods relating thereto. The microparticles are distinguishable based on differences in dielectric response to an applied electric field. In different embodiments, the dielectric differences may be engineered through, but not limited to, dielectrically dispersive materials, surface charge, and/or fluorescence. Gangliosides may be incorporated with the microparticles to control aggregation. Vesicles including erythrocyte ghosts may be used as a basis for microparticles. The microparticles may utilize a biotin streptavidin system for surface functionalization.
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Excerpt(s): Methodology of the current disclosure may be used with the apparatuses and methods described in U.S. Pat. No. 6,294,063, which is expressly incorporated herein by reference. Other patents and applications that may be used in conjunction with the current disclosure include U.S. Pat. No. 5,858,192, entitled "Method and apparatus for manipulation using spiral electrodes," filed Oct. 18, 1996 and issued Jan. 12, 1999; U.S. Pat. No. 5,888,370 entitled "Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation," filed Feb. 23, 1996 and issued Mar. 30, 1999; U.S. Pat. No. 5,993,630 entitled "Method and apparatus for fractionation using conventional dielectrophoresis and field flow fractionation," filed Jan. 31, 1996 and issued Nov. 30, 1999; U.S. Pat. No. 5,993,632 entitled "Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation," filed Feb. 1, 1999 and issued Nov. 30, 1999; U.S. patent application Ser. No. 09/395,890 entitled "Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation," filed Sep. 14, 1999; U.S. patent application Ser. No. 09/883,109 entitled "Apparatus and method for fluid injection," filed Jun. 14, 2001; U.S. patent application Ser. No. 09/882,805 entitled "Method and apparatus for combined magnetophoretic and dielectrophoretic manipulation of analyte mixtures," filed Jun. 14, 2001; U.S. patent application Ser. No. 09/883,112 entitled "Dielectrically-engineered microparticles," filed Jun. 14, 2001; and U.S. patent application Ser. No. 09/883,110 entitled "Systems and methods for cell subpopulation analysis," filed Jun. 14, 2001, each of which are herein expressly incorporated by reference. Yet another application that may be used in conjunction with the teachings of the current invention include those described in "Micromachined impedance spectroscopy flow cytometer of cell analysis and particle sizing," Lab on a Chip, vol. 1, pp. 76-82 (2001), which is incorporated by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Homogeneous immunoassays for multiple allergens Inventor(s): Brown, Christopher R.; (San Mateo, CA), Murai, James T.; (San Bruno, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030109067 Date filed: December 6, 2001 Abstract: A homogeneous immunoassay method and system for quantitative determination of total immunoglobulin E and specific antibody levels to a plurality of allergens, in which a relatively small sampling of blood is required. The method utilizes relatively small microparticles in suspension with 1-5.mu.L of undiluted sample. The immunoassay procedure is an immunometric sandwich procedure preferably utilizing biotin-streptavidin signal amplification techniques and R-phycoerytherin fluorescent labels. Excerpt(s): This invention relates to a homogenous immunoassay method for determining specific antibody levels to a multiplicity of allergens from a blood sample, or for determining total immunoglobulins E levels in such a sample, for the purpose of diagnosing allergy. Confirmatory diagnostic testing may be conducted by in-vivo skin testing, in-vivo provocation testing, or in-vitro testing for the presence of circulating allergen-specific antibodies from blood samples. Direct provocation, by direct inhalation or ingestion of possible offending allergens, while relevant, is unpleasant, possibly dangerous and cannot be performed for multiple allergens at one sitting. Skin testing
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(also referred to as skin prick testing or scratch testing) is an in vivo procedure that involves applying an allergen sample, or more generally a multiplicity of allergens, directly to a patient's forearm or back via a small needle scratch and measuring the size of the inflammatory reaction (wheal) at the applied site on the skin. Skin prick testing is widely used, is reliable under optimal testing conditions, can be painful, is subject to large differences in technique and interpretations, and cannot be used on patients taking certain drugs or patients with skin problems. Furthermore, both provocation and skin prick in-vivo diagnostic methods have the potential for sensitizing patients to new allergens and, in extreme cases, eliciting a life-threatening anaphylactic reaction upon direct exposure to the offending allergen(s). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Insect resistant transgenic plants expressing biontin-binding protein gene Inventor(s): Bailey, Michele; (College Station, TX), Howard, John; (College Station, TX) Correspondence: Arent Fox Kintner Plotkin & Kahn; 1050 Connecticut Avenue, N.W.; Suite 400; Washington; DC; 20036; US Patent Application Number: 20030213011 Date filed: April 11, 2003 Abstract: Methods of controlling insect infestation of plants using a nucleotide sequence encoding biotin-binding protein to produce high levels of biotin-binding protein in the plant, i.e., a mean concentration of.gtoreq.100 ppm. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to U.S. provisional application Serial No. 60/204,639, filed May 17, 2000. This application is directed to methods of controlling insect infestation of plants using a nucleotide sequence encoding a biotin-binding protein to produce high levels of the protein in the plant. The output of world agriculture must increase if the demands of a rising population are to be met. To preserve more of what is grown, genetic engineering has been utilized to produce transgenic crops that contain proteins detrimental to critical life functions of pests and pathogens. See, e.g., Hilder and Boulter, Crop Protec. 18, 177-191 (1999). One of the first commercially successful transgenic food crops is maize, which is resistant in the field to corn borers because it contains toxins produced by the soil bacterium Bacillus thuringiensis (Bt). See, e.g., U.S. Pat. No. 5,322,687. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Magnetic fine particles having lower critical solution temperature Inventor(s): Furukawa, Hirotaka; (Yokohama-shi, JP), Kataoka, Kazunori; (Tokyo, JP), Ohnishi, Noriyuki; (Yokohama-shi, JP), Ueno, Katsuhiko; (Tsukuba-shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030165962 Date filed: February 21, 2003 Abstract: The present invention relates to magnetic fine particles having a lower critical solution temperature to which at least one substance selected from biotin and avidin is immobilized, and a method of converting a substance, a method of separating or
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concentrating a microorganism, a method of modifying a denatured protein, a method of detecting a nucleic acid, a separating agent, and a method of separating a biological substance using the same. Excerpt(s): The present invention relates to magnetic fine particles having a lower critical solution temperature, and a method of converting a substance, a method of separating or concentrating a microorganism, a method of modifying a denatured protein, a method of detecting a nucleic acid, a separating agent, and a method of separating a biological substance, each using the magnetic fine particles. As described in Clin. Microbiol. Rev., 1994, pp. 43-54, there are many attempts to separate a variety of biological molecules and microorganisms by immobilizing antibodies or pairing bases to magnetic fine particles. As the magnetic fine particles for use in these methods, those having a particle size of 1.mu.m or more are usually used in consideration of the time for recovering them with a magnet. However, since the surface area decreases as the particle size increases, the efficiency is a big problem in the case that a small molecule such as a protein or nucleic acid is tried to separate. As a method for solving the problem of particle size, Applied. Microbiol. Biotechnol., 1994, Vol. 41, pp. 99-105 and Journal of fermentation and Bioengineering, 1997, Vol. 84, pp. 337-341 have reported that magnetic fine particles having a lower critical solution temperature (hereinafter referred to as "LCST") and a particle size of about 100 to 200 nm are obtained by polymerizing polyisopropylacrylamide having an LCST in the presence of magnetic fine particles and that the magnetic fine particles is possible to recover easily through their aggregation caused by raising the solution temperature to the LCST or higher even though the particle size of the magnetic fine particles is smaller than that of conventional particles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for recognizing molecular compounds Inventor(s): Han, Shubo; (Alhambra, CA), Ralin, David; (San Gabriel, CA), Rassman, William; (Los Angeles, CA), Zhou, Feiming; (Temple City, CA) Correspondence: Marvin H. Kleinberg; Kleinberg & Lerner, Llp; Suite 1080; 2049 Century Park East; Los Angeles; CA; 90067; US Patent Application Number: 20030224370 Date filed: May 31, 2002 Abstract: A probe-target reaction is made more recognizable by the provision of a massenhancing and/or evanescent-field-perturbing amplifier element which reacts uniquely with and binds to the probe-target pair to provide increased mass. Where the probetarget pair is hybridized dsDNA, a suitable mass-enhancing amplifier is anti-double stranded DNA mouse IgM. In examples with sufficient sequence pairs in the probetarget combination, a sequence-specific minor-groove-binding polyamide can be used that carries biotin which can be amplified by streptavidin in a suitable carrier. In a preferred embodiment, a plurality of probes are immobilized at the sites of a microarray, each probe being specific to a different target. Optics utilizing total internal reflection are described for observing perturbation of the evanescent field. Excerpt(s): The present invention relates to methods and apparatus for detecting, qualitatively and quantitatively, molecular interaction. To help describe the prior art and the present invention, it is deemed useful to provide a glossary of terms that will be used herein. A "probe" is intended to mean a known entity which may either be
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immobilized or free floating. A "target" or "ligand" is an "unknown" entity which has a known, specific complementary or reactive relationship with a specific probe. Probetarget combinations may be referred to as "complexes" or "pairs". A "primary amplifier" or "mass enhancing unit" is a "bulky" entity which has an interaction or bonding with a pair, or with a linking element that bonds to the pair. A "secondary amplifier" interacts with the primary amplifier or with the combination of primary amplifier-probe-target pair complex to form a new combination. A "tertiary amplifier" is any successive mass enhancer which can interact with a primary amplifier-probe-target pair complex or amplifier. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for detecting biopolymers Inventor(s): Iwao, Kanako; (Tokyo, JP), Kuwabata, Susumu; (Osaka, JP), Morita, Toshiki; (Tokyo, JP), Nakao, Motonao; (Tokyo, JP), Sato, Keiichi; (Tokyo, JP) Correspondence: Reed Smith Hazel & Thomas Llp; Suite 1400; 3110 Fairview Park Drive; Falls Church; VA; 22042-4503; US Patent Application Number: 20030162215 Date filed: February 26, 2003 Abstract: A technique is provided that easily detects biopolymers such as a DNA or a protein by utilizing semiconductor nanoparticles having different excitation wavelengths and fluorescence due to differences in particle size. By binding the semiconductor nanoparticles with avidin (or biotin), detection of biopolymers labeled with biotin (or avidin) is enabled. Excerpt(s): The present invention relates to a technique in which a semiconductor nanoparticle is bound to a molecule for detection, such as avidin, streptavidin or biotin, for detecting, as a fluorescent substance, a biopolymer such as a polynucleotide or a protein or the like. First, RT-PCR of mRNA is performed using reverse transcriptase. At this time, Cy3-dUTP or Cy5-dUTP is incorporated and unreacted dUTP is removed to prepare the target cDNA. Next, hybridization of the target cDNA with cDNA on a DNA chip is conducted. Finally, a laser beam is irradiated onto the DNA chip to detect fluorescence with wavelength. A laser beam having an excitation wavelength of 552 nm is irradiated for Cy3, and a laser beam having an excitation wavelength of 650 nm is irradiated for Cy5. However, in the above-described method, Cy3 and Cy5 are individually excited by their respective lasers, and it is only possible to detect one fluorescence with wavelength at a time. In other words, it is only possible to detect the fluorescence with wavelength corresponding to one excitation wavelength. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for producing micro-carrier and test method by using said micro-carrier Inventor(s): Chang, Rong-Seng; (Chungho City, TW), Chao, Yu-Chan; (Chungho City, TW) Correspondence: Richard E. Fichter; Bacon & Thomas, Pllc; Fourth Floor; 625 Slaters Lane; Alexandria; VA; 22314-1176; US Patent Application Number: 20030059804 Date filed: May 29, 2002 Abstract: The invention provides a method for producing a microcarrier, which includes patterning pluralities of bar code on a mask; exposing the bar code to a substrate coated with photoresist; etching and removing residual photoresist and electroforming to a nickel plate; placing a bead coated with biotin or poly-L-lysine between two-nickel plates, and compressing the bar code on the surface of the bead to form a microcake-like particle with bar code; and combining the is particle with the corresponding biomolecule thereof to produce a micro-carrier with a label. The invention also provides a test method for identifying a bio-molecule, which includes mixing several micro-carriers with the labeled unknown bio-molecules; and identifying the bar code on the microcarrier via image recognition system, wherein the numbers and types of the known micro-carrier can be flexibly adjusted. Excerpt(s): The present invention relates to a method for preserving and testing biologically genetic information, and particularly to a micro-carrier and a test method for identifying unknown bio-molecules such as DNA or proteins by using a code labeled micro-carrier. Biotechnology has been developing quickly in recent years. Various products can be produced using molecular biology, biological cells, or other metabolites thereof by this technique, which can be extensively applied in the fields of pharmaceutical, pesticide, environmental protection, process development, and aquaculture. The combination of biotechnology with electric technology is a trend; wherein the most attractive is the biochip and DNA chip (i.e. gene chip). In addition to silicon, the material of those chips can include absorbent materials such as glass, plant cellulose, gel, and organic polymers. The gene chip has various gene fragments neatly aligned and adhered onto a nail-sized chip, in which thousands upon thousands of gene fragments are accommodated. Users can select different kinds of gene chips based on their purposes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for sequence specific biotinylation Inventor(s): Ambrosius, Dorothee; (Muenchen, DE), Lanzendoerfer, Martin; (Muenchen, DE), Schraeml, Michael; (Muenchen, DE), Watzele, Manfred; (Weilheim, DE) Correspondence: Hoffmann-la Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030092073 Date filed: September 20, 2002 Abstract: A method of preparing a biotinylated polypeptide in a cell-free peptide synthesis reaction mixture by contacting, under suitable conditions, a polypeptide to be biotinylated, with a reaction mixture that includes ribosomes, tRNA, ATP, GTP, nucleotides, biotin and amino acids, and a polypeptide that includes an enzymatically
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active domain of a BirA enzyme. The polypeptide to be biotinylated includes a BirA substrate sequence tag, and the polypeptide to be biotinylated and the polypeptide comprising an enzymatically active domain of a BirA enzyme, are expressed in situ in the reaction mixture, by at least one nucleic acid molecule encoding the polypeptide to be biotinylated, and the enzymatically active domain of a BirA enzyme, respectively. Excerpt(s): The invention relates to an improved method for sequence specific biotinylation of polypeptides. The enzyme biotin haloenzyme synthetase of Eschericia coli ("E. coli"), is a biotin ligase (hereinafter also referred to as "BirA") that is the product of the qrA gene (Cronan, J. E., Jr., Cell 58 (1989) 427-429). BirA catalyzes the covalent addition of biotin, in vivo, to the.epsilon.-amino group of a lysine side chain in its natural substrate, biotin carboxyl carrier protein ("BCCP") (Cronan, J. E., Jr., et al., J. Biol. Chem. 265 (1990) 10327-10333). BCCP is a subunit of acetyl-CoA carboxylase and, in E. coli, BCCP is biotinylated. Biotinylation of proteins using a biotinylation enzyme by recombinant means is described, e.g., in WO 95/04069, incorporated by reference herein. Sequence specific enzymatic biotinylation, (also referred to herein as "specific biotinylation" or preparing, "specifically biotinylated" polypeptides) using BirA is also described for recombinant polypeptides during expression in E. coli (Tsao, K.-L., et al., Gene 169 (1996) 59-64), incorporated by reference herein. Altman, J. D., et al., Science 274 (1996) 94-96, incorporated by reference herein, describe the enzymatic biotinylation of isolated polypeptides in vitro, using also BirA. However, such a method is very laborious, requiring considerably more purification steps compared to conducting the biotinylation in vivo. First, the protein must be prepared, isolated and purified. Subsequently, biotinylation is performed, and thereafter, another purification is carried out. Parrott, M. B., and Barry, M. A., in Biochem. Biophys. Res. Communications 281 (2001) 993-1000, incorporated by reference herein, describe the metabolic biotinylation of secreted and cell-surface proteins from mammalian cells using the endogenous biotin ligase enzymes of the mammalian cell. Saviranta, P., et al., in Bioconjug. Chem. 9 (1998) 725-735, incorporated by reference herein, describe the in vitro enzymatic biotinylation of recombinant Fab fragments through a peptide acceptor tail. The proteins were recombinantly produced in E. coli, purified and subsequently biotinylated in vitro with BirA. After the removal of non-biotinylated Fab fragments, the overall yield of biotinylated Fab was 40%. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multiple antioxidant micronutrients Inventor(s): Haase, Gerald M.; (Greenwood Village, CO), Prasad, Kedar N.; (Denver, CO) Correspondence: Ostrolenk, Faber, Gerb & Soffen, Llp; 1180 Avenue OF The Americas; New York; NY; 10036-8403; US Patent Application Number: 20030147996 Date filed: August 28, 2002 Abstract: A method for optimizing the health of humans according to their age and sex is disclosed wherein the method comprises administering to said humans a daily dose of a multiple antioxidant micronutrient composition comprising vitamin A (palmitate), beta-carotene (from natural d. salina), vitamin C (calcium ascorbate), vitamin D-3 (cholecalciferol), natural source vitamin E including both d-alpha tocopherol and dalpha tocopheryl acid succinate, thiamine mononitrate, riboflavin, niacinamide ascorbate, d-calcium pantothenate, pyridoxine hydrochloride, cyanocobalamin, folic
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acid (folacin), d-biotin, selenium (l-seleno methionine), chromium picolinate, zinc glycinate, calcium citrate, and magnesium citrate.For persons over the age of about 51, the composition preferably further comprises one or more of co-enzyme Q.sub.10, Nacetyl cysteine, and alpha lipoic acid. Preferably, also, vitamin D is added for women over the age of about 36. Excerpt(s): We claim the benefit under Title 35, United States Code,.sctn.120 of U.S. Provisional Application No. 60/315,523, filed Aug. 29, 2001, entitled MULTIPLE ANTIOXIDANT MICRONUTRIENTS FOR OPTIMAL HEALTH. In the beginning, the earth's atmosphere had no oxygen. Anaerobic organisms, which can live without oxygen, were thriving. About 2.5 billion years ago, blue-green algae in the ocean acquired the ability to split water into hydrogen and oxygen and this chemical reaction initiated the release of oxygen into the atmosphere. The increased levels of atmospheric oxygen caused extinction of many anaerobic organisms owing to oxygen's toxicity. This important biological event also led to the evolution of multicellular organisms, including humans, who utilize oxygen for survival. The content of oxygen in the air gradually increased to the current amounts of about 21 percent in dry air and about 34 percent in water. The use of oxygen by any organism generates free radicals that are toxic. Therefore, during this period of atmospheric oxygenation, organisms must have struggled to survive the sudden exposure to oxygen toxicity. There must have been enormous rearranging of nucleotides in genes to produce specific proteins that could protect organisms against the damage produced by free radicals. This process eventually led to the production of three antioxidant enzymes. Superoxide dismutase (SOD) requires manganese, copper, or zinc for its biological activity. Mn-SOD is present in mitochondria, whereas Cu-SOD and Zn-SOD are present in the cytoplasm and nucleus of the cell. All three can destroy free radicals and hydrogen peroxide. Another enzyme, catalase, requires iron for its biological activity and it destroys H.sub.2O.sub.2 in cells. Human tissue also contains glutathione peroxidase which requires selenium for its biological activity. It is also responsible for removing hydrogen peroxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multi-vitamin and hormone replacement supplement Inventor(s): Fox, Dorothy Jean; (Chesapeake, VA), Schloss, Caroline Maxine; (Knotts Island, NC) Correspondence: Kimberly A Chasteen; Williams Mullen Clark & Dobbins; One Iod Oyster Point Road; Suite 210; Newport News; VA; 23602 Patent Application Number: 20030096018 Date filed: September 23, 2002 Abstract: A supplement is disclosed for use by naturally or surgically menopausal women. The supplement includes: Estrogen, Selenium, Zinc, Chromium, Calcium, Copper, Phosphorus, Magnesium, Molybdenum, Iodine, Beta Carotene, Ascorbic Acid, Vitamin D, Vitamin E, Vitamin K, Thiamin, Riboflavin, Vitamin B6, Vitamin B12, Folic Acid, Iron, Pantothenic Acid, and Biotin. The supplement provides hormone replacement therapy along with nutritional supplements. Excerpt(s): The present invention relates generally to a pharmaceutical supplement for menopausal women and more specifically to a pharmaceutical supplement which combines the hormone estrogen with daily supplemental vitamins to treat menopausal women and women who have undergone complete hysterectomies as more fully set
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forth in the below specifications, drawings and claims. It is well known that estrogen is critical to a woman's health in that it helps to protect the cardiovascular system, helps protect against bone loss and aids mental sharpness. At menopause or subsequent to a complete hysterectomy, the estrogen levels decline significantly thus, the protective aspects of estrogen are significantly reduced for these women. Because heart disease is a major cause of death in women, this creates an increased risk for menopausal and posthysterectomy women. Further, loss of the protection against bone loss can lead to osteoporosis, another major problem for these women. The impairment of cognitive abilities can be another side effect of the significant estrogen loss suffered in menopause or post-hysterectomy. Additional side effects have been linked to reduced estrogen levels such as urinary incontinence and weight gain. Many women are treated with hormone replacement therapy to help reduce these symptoms. The treatment generally consists of supplemental estrogen. This reduces the problems noted above, heart disease, bone loss, loss of cognitive ability, urinary incontinence, weight gain, as well as other well-known symptoms such as hot flashes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nutritive media and manufactured seeds comprising same Inventor(s): Carlson, William C.; (Olympia, WA), Grob, James A.; (Auburn, WA), Hartle, Jeffrey E.; (Milton, WA), Heilesen, Mollie K.; (Tacoma, WA), Salatas, Katherine M.; (Tacoma, WA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20030167684 Date filed: February 20, 2003 Abstract: Manufactured seeds are disclosed that comprise a unit of totipotent plant tissue and a nutritive medium. The nutritive medium can contain a number of different components selected from the following: a gel solute, charcoal, a carbon source, urea, KNO.sub.3, NH.sub.4NO.sub.3, CuCl.sub.2, CuSO.sub.4, KI, KH.sub.2PO.sub.4, CaCl.sub.2, MgSO.sub.4, Na.sub.2EDTA, FeSO.sub.4, ferric citrate, MnSO.sub.4, MnCl.sub.2, H.sub.3BO.sub.3, ZnSO.sub.4, CoCl.sub.2, Na.sub.2MoO.sub.4, (NH.sub.4).sub.2MoO.sub.4, thiamine, riboflavin, pyridoxine, HCl, Ca-pantothenate, nicotinic acid, biotin, folic acid, and myo-inositol. The nutritive medium can also include any of various protein amino acids, any of various polyamines, any of various oxygen-absorbing compounds, any of various non-protein amino acids, and/or a smoke suspension. Excerpt(s): This application is a divisional application of U.S. patent application Ser. No. 09/529,933, filed Apr. 21, 2000, now abandoned, which claims the benefit under 35 U.S.C.sctn.365(c) of PCT/US98/24820, filed Nov. 20, 1998, which claims the benefit under U.S.C.sctn.119(e) of U.S. Provisional Patent Application Serial No. 60/066,232, filed Nov. 20, 1997, the disclosures of all are hereby expressly incorporated by reference. The invention pertains to nutritive media, methods for using such media in the production of manufactured seeds, and manufactured seeds comprising same. In many instances it is desirable to grow large numbers of genetically identical plants. These plants can be selected and grown based on their particular qualities, such as their ability to grow in a particular climate, or their ability to produce a particular type or quality of fiber. Unfortunately, in many cases the production of such plants through standard breeding is not feasible.
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Patterned biological molecules on inner surface of enclosed tubes Inventor(s): Craighead, Harold G.; (Ithaca, NY), Orth, Reid N.; (Ithaca, NY), Turner, Stephen W.; (Ithaca, NY) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030153010 Date filed: January 9, 2003 Excerpt(s): This application claims the benefit of priority under 35 U.S.C. 119(e) to U.S. Provisional Patent Application Serial No. 60/347,622, filed Jan. 10, 2002, which is incorporated herein by reference in its entirety. Many micro and nanotechnology bioassay applications such as biosensor/chromatography systems require protein patterning to operate effectively. Biological samples must be fixed in place on a desired surface. Several methods have been developed to fix such samples on glass surfaces. However, some such techniques require large quantities of the biosample. Attempts have been made to apply the samples, and then enclose them with a glass plate. Unfortunately, the adhering process used to achieve adequate sealing also produced high heat, that adversely affected such samples. Biomolecular photo-based patterning methods utilize avidin-biotin technology to immobilize functional proteins on the inner surface of silica glass tubes in desired patterns. The methods are useful for nanofluidic affinity biosensor/chromatography systems and on silicon dioxide substrates for biosensor applications. The resulting patterns are optimized based on the application. In one embodiment, a zebra shaped pattern is utilized for an affinity chromatography system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Plant biotin synthase Inventor(s): Allen, Stephen M.; (Wilmington, DE), Kinney, Anthony J.; (Wilmington, DE), Miao, Guo-Hua; (Johnston, IA), Orozco, Emil M. JR.; (West Grove, PA) Correspondence: Connolly Bove Lodge & Hutz, Llp; 1220 N Market Street; P O Box 2207; Wilmington; DE; 19899 Patent Application Number: 20030192073 Date filed: May 7, 2003 Abstract: This invention relates to an isolated nucleic acid fragment encoding a biotin synthases. The invention also relates to the construction of a chimeric gene encoding all or a portion of the biotin synthases, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the biotin synthases in a transformed host cell. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/172,929, filed Dec. 21, 1999. This invention is in the field of plant molecular biology. More specifically, this invention pertains to nucleic acid fragments encoding biotin synthase in plants and seeds. Biotin is an essential component for all living organisms even though many, including humans, cannot synthesize biotin and are dependent
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upon its uptake from their environment or diet (Eisenberg (1973) Adv Enzymol 38:317372, Pai (1975) J Bacteriol 121:1-8). Biotin serves as a cofactor that covalently binds to carboxylases and facilitates the transfer of carboxyl groups during enzymatic reactions involving carboxylation, decarboxylation and transcarboxylation (Dakshinamurti and Bhagavan, eds., (1985) "Biotin", Ann NY Acad Sci 447:1-441; Knowles (1989) Ann Rev Biochem 58:195-221). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Polynucleotide motor, a motor system, their preparation and uses Inventor(s): Firman, Keith; (Portsmouth, GB) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20020160485 Date filed: November 26, 2001 Abstract: A polynucleotide motor is disclosed, comprising an enzyme capable of binding to a nucleic acid sequence, which enzyme is also capable of translocating the nucleic acid sequence without causing cleavage thereof. The motor may be associated with a substance bound to the nucleic acid sequence so that the bound substance, such as a magnetic bead, biotin, streptavidin, a scintillant or the like, can itself be translocated, relative to the region of binding of the enzyme, during translocation. Such a system has applications in the screening or testing for a pre-determined biological, chemical or physical activity; for example, in screening for new pharmacologicallyeffective ligands. Excerpt(s): The present invention relates to a nucleic acid sequence having bound thereto a particular complex involving a subunit of a restriction endonuclease, which complex is capable of translocating the polynucleotide without causing cleavage thereof; and its use, inter alia, in a molecular machine system. Molecular machines have been described as molecules--on a nanometric scale--that have moving parts and do useful work. A molecular machine system may therefore be a multi-component molecular machine. For such a machine or machine system to operate successfully, it must be based on a compact, stable molecular structure. Accordingly, theoretical studies of molecular machine systems have focused on inflexible, covalent structures, such as graphite- and diamond-like materials, working in a vacuum. However, it is unlikely that such theoretical systems can be built, in practice, in the near future. On the other hand, the art of preparing polymeric structures is comparatively well-advanced. The drawback of these, however, is that they must fold appropriately in order to provide a usable structure. Protein folds, for example, are difficult to design in view of the lack of strong, natural complementarity of individual amino acids. Contrastingly, work has been carried out which shows that it is possible to design DNA-based structures, so that nucleic acids could be engineered to serve as scaffolds for complex molecular motor-and other--systems. The problem then is to provide a suitable motor or machine system that can appropriately interact with a DNA-based structure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Polysaccharides with antithrombotic activity comprising at least a covalent bond with biotin or a biotin derivative Inventor(s): Duchaussoy, Phillppe; (Toulouse, FR), Herbert, Jean-Marc; (Tournefeuille, FR), Petitou, Maurice; (Paris, FR), Savi, Pierre; (Seysses, FR) Correspondence: Sanofi-synthelabo INC.; 9 Great Valley Parkway; P.O. Box 3026; Malvern; PA; 19355; US Patent Application Number: 20040024197 Date filed: March 21, 2003 Abstract: The present invention relates to novel synthetic polysaccharides with antithrombotic activity exhibiting at least one covalent bond with biotin or a biotin derivative and to a process employing avidin or streptavidin which makes it possible to neutralize these polysaccharides. Excerpt(s): The present invention relates to novel synthetic oligo- and polysaccharides exhibiting at least one covalent bond with biotin or a biotin derivative and having the anticoagulant and antithrombotic pharmacological activities of heparin. Heparin catalyses, in particular via antithrombin III (AT III), the inhibition of two enzymes which are involved in the blood coagulation cascade, namely factor Xa and factor IIa (or thrombin). Preparations comprising low molecular weight heparins (LMWHs) comprise chains formed of 4 to 30 monosaccharides and have the property of acting more selectively with respect to factor Xa than with respect to thrombin. It is known that the inhibition of factor Xa requires attachment of heparin to AT III via the antithrombinbinding domain (Domain-A) and that inhibition of factor IIa (thrombin) requires attachment to AT III, via the Domain-A, and to thrombin via a less well defined binding domain (Domain-T). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pretargeting methods and compounds Inventor(s): Axworthy, Donald B.; (Brier, WA), Reno, John M.; (Brier, WA), Theodore, Louis J.; (Lynnwood, WA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20030129191 Date filed: April 17, 2002 Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Clearing agents and clearance mechanisms are also discussed. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 163,184, filed on Dec. 7, 1993, which is a continuation-in-part of pending PCT Patent Application No. PCT/US93/05406, filed Jun. 7, 1993 and designating the United States, which, in turn, is a continuation-in-part of pending U.S. patent application Ser. No. 07/995,381, filed Dec. 23, 1992, which is, in turn, a continuation-in-part of pending U.S. patent application Ser. No. 07/895,588, filed Jun. 9, 1992. All of these applications are incorporated by reference in their entirety herein. The present invention relates to methods, compounds, compositions and kits useful for delivering to a target site a
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targeting moiety that is conjugated to one member of a ligand/anti-ligand pair. After localization and clearance of the targeting moiety conjugate, direct or indirect binding of a diagnostic or therapeutic agent conjugate at the target site occurs. Methods for radiometal labeling of biotin or other small molecules, as well as the related compounds, are also disclosed. Clearing agents and clearance mechanisms are discussed, which agents or mechanisms facilitate a decrease in the serum half-life of targeting moiety-ligand or targeting moiety-anti-ligand conjugates. Conventional cancer therapy is plagued by two problems. The generally attainable targeting ratio (ratio of administered dose localizing to tumor versus administered dose circulating in blood or ratio of administered dose localizing to tumor versus administered dose migrating to bone marrow) is low. Also, the absolute dose of radiation or therapeutic agent delivered to the tumor is insufficient in many cases to elicit a significant tumor response. Improvement in targeting ratio or absolute dose to tumor is sought. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for preparation full-length cDNA and anchor used for the same Inventor(s): Jang, Mi-Sook; (Chungbuk, KR), Jeon, Jin-Tae; (Chungbuk, KR), Park, HanOh; (Chungbuk, KR) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030049637 Date filed: November 21, 2001 Excerpt(s): The present invention relates to a process for the preparation of full-length complementary DNA (cDNA). More particularly, the present invention is directed to a process for selective amplification of full-length cDNA, which comprises: i) a step for preparing a hybrid composed of a messenger RNA (mRNA) strand and a cDNA strand of which three (3) or four (4) deoxycitidinemono phosphate (dCMP) are combined at 3' end, by treating mRNA with reverse transcriptase; separately from the above step, ii) a step for adenylating single strand anchor of which biotin or phosphate group is combined at 3' end, and phosphate group is combined at 5' end; iii) a step for ligating said adenylated single strand anchor to 3' end of full-length cDNA strand of said cDNA/mRNA hybrid to select full-length cDNA/mRNA hybrid; and iv) a step for amplifying only the full-length cDNA/mRNA hybrid through polymerase chain reaction (PCR) which employs a primer of which base sequence is complementary to that of said anchor. Recently, new techniques for mass production of various genetic engineering products such as proteins, have been developed through identification of novel genes and determination of base sequences thereof, and then characterization of their biological properties. In addition, some methods for the treatment of various diseases caused by inappropriate expression and/or suppression of a specific gene or by the influence of foreign substance such as carcinogen or teratogen, can be developed through the analysis of the base sequences of the gene. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 187
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Production of biotin Inventor(s): Asakura, Akira; (Fujisawa-shi, JP), Hoshino, Tatsuo; (Kamakura-shi, JP), Kiyasu, Tatsuya; (Fujisawa-shi, JP), Nagahashi, Yoshie; (Fujisawa-shi, JP) Correspondence: Mark E. Waddell, ESQ.; Bryan Cave Llp; 245 Park Avenue; New York; NY; 10167-0034; US Patent Application Number: 20030096382 Date filed: March 22, 2001 Abstract: The present invention provides process for making biotin from desthiobiotin either contacting desthiobiotin with an enzyme reaction mixture containing bioB gene product and nifU gene product and/or nifS gene product and isolating the biotin or cultivating a microorganism transformed with DNA encoding the bioB gene product, nifU gene product and nifS gene product and isolating the biotin. Excerpt(s): Biotin is one of the essential vitamins for nutrition of animals, both human and non-human, plants, and microorganisms, and very important as a medicine or food additive. There are many studies on fermentative production of biotin. Escherichia strains are known as microorganisms which can be used for the above process [see Japanese Patent Publication (Kokai) No. 149091/1986, WO 87/01391 and Japanese Patent Publication (Kokai) No. 155081/1987 ]. In addition to the above-mentioned strains, Bacillus strains [Japanese Patent Publication (Kokai) No. 180174/1991), Serratia strains [Japanese Patent Publication (Kokai) No. 27980/1990] and Brevibacterium strains [Japanese Patent Publication (Kokai) No. 240489/1991] are also known. But these processes have not yet been suitable for industrial use because of the low efficiency of carbon recovery from the nutrients into biotin and, in some cases, the accumulation of the direct intermediate, desthiobiotin. It is therefore desirable to improve the efficiency of the conversion of desthiobiotin to biotin. A conversion reaction of desthiobiotin to biotin using the resting cell system of Escherichia coli (Antimicrob. Agents Chemother. 21, 5, 1982) and one using cell-free extract of Escherichia coli [J. Biol. Chem., 270, 19158 (1995); Biosci. Biotechnol. Biochem., 56, 1780 (1992); Eur. J. Biochem., 224, 173 (1994); Arch. Biochem. Biophys., 326, 48 (1996)] are known. According to these publications, it has been clarified that protein factors such as ferredoxin-NADP reductase and flavodoxin together with biotin synthase are involved in the biotin formation from desthiobiotin. Nevertheless, only limited effect has been observed for biotin production from desthiobiotin under these conditions. It was simply speculated that another unknown protein should be involved in this reaction to more efficiently convert desthiobiotin to biotin. Furthermore, a conversion reaction by using the purified biotin synthase of Bacillus sphaericus with photoreduced deazaflavin as an artificial electron donor instead of using physiological electron transfer system of ferredoxin-NADP reductase and flavodoxin has recently been reported [Biochem. Biophys. Res. Commun., 217, 1231 (1995)]. But the reported reaction efficiency is not high enough for the reaction to be usable in the industrial production of biotin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Secretions of proteins by encapsulated cells Inventor(s): Akselband, Yevgenya; (Brighton, MA), Jesperson, Diana; (Malvern, NJ), McGrath, Patricia; (Cambridge, MA), Moen, Phillip T.; (Foxborough, MA), Trnovsky, Jan; (Saugus, MA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030143642 Date filed: May 28, 2002 Abstract: The invention provides methods of analzying a secreted protein from a cell encapsulated in a microdrop. The microdrop is formulated with biotinylated matrix molecules at a reduced ratio of biotin to matrix molecules compared with previous formulations. The reduced ratio is advantageous for improving the resolution of detection and allows simultaneous detection of multiple secreted proteins and/or multiple cell surface markers. The invention further provides inter alia methods of isolating IgG isotype antibodies that have switched from IgM isotype. Excerpt(s): The present application derives priority from U.S. S No. 60/293,822 filed May 26, 2001, which is incorporated by reference in its entirety for all purposes. The gel microdrop (GMD) secretion assay involves encapsulating cells in a biotinylated matrix, followed by capture and detection of cell-secreted molecules with fluorescent markers (17-34). This technology differs from other encapsulation methods in that the small size of the microdrop (e.g., <50.mu.m diameter) creates a defined microenvironment around the cell without impeding diffusion of nutrients, antibodies, or nucleic acid probes into the microdrops, or diffusion of secreted products. Furthermore, microdrops can readily be analyzed using flow cytometry and sub-populations can be detected. The number of occupied cells in each microdrop preparation depends on the number of cells used for encapsulation and is approximated by Poisson statistics for single cell encapsulation (19). To obtain microdrops having a high probability of initially containing 0 or 1 cells, an experimental protocol has been developed in which 1-1.5 million cells are encapsulated in 20 million microdrops, resulting in approximately 5-10% single cell occupation. The emulsion is transiently cooled, causing the drops to gel. Once gelled, the microdrops are physically distinct and robust and can be removed from the oil into an aqueous medium by low speed centrifugal separation. Since the microdrop agarose matrix is a permeable semi-solid support, immunochemical procedures can be performed on encapsulated cells. The invention provides methods of analzying a secreted protein. Such method entail encapsulating a cell in a microdrop wherein the microdrop comprises matrix component molecules, first biotin molecules linked to the matrix component molecules, capture molecules with affinity for a molecule secreted by the cell linked to second biotin molecules, and streptavidin linking the first and second biotin molecules, the first biotin molecules and the matrix component molecules being in a molar ratio of less than 0.85, preferably 0.01 to 0.2, and optionally 0.02-0.2 moles biotin per mole matrix component molecules. The molecule is secreted from the cell and binds to the capture molecules is thereby retained within the microdrop. The secreted molecule is then detected. In some methods the concentration of the first biotin molecules in the microdrop is less than or equal to 42 micromolar. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 189
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Sequencing of surface immobilized polymers utilizing microfluorescence detection Inventor(s): Dower, William J.; (Menlo Park, CA), Fodor, Stephen P.A.; (Palo Alto, CA) Correspondence: Townsend And Townsend And Crew Llp; Two Embarcadero Center; 8th Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030008302 Date filed: February 14, 2002 Abstract: Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal manomers on solid phase immobilized polymers. Reagents which specifically recognize terminal manomers are used to label polymers at defined positions on a solid substrate.This is a continuation-in-part application of commonly assigned patent application by Pirrung et al., U.S. Ser. No. 07/362,901 (VLSIPS parent), filed Jun. 7, 1989; and Pirrung et al., U.S. Ser. No. 07/492,462, "Very Large Scale Immobilized Polymer Synthesis", filed on Mar. 7, 1990, and which is incorporated herein by reference. Related cases Barrett et al., U.S. Ser. No. 07/435,316 (caged biotin parent), filed on Nov. 13, 1989, and Barrett et al, U.S. Ser. No. 07/612,671 (caged biotin CIP), filed on Nov. 13, 1990, are also incorporated herein by reference. Additional applications Fodor et al., U.S. Ser. No. ______, attorney docket number 11509-28 ______, (automated VLSIPS); and Fodor et al., U.S. Ser. No. ______, attorney docket number 11509-30 (sequencing by hybridization), are filed on the same day as this application and incorporated herein by reference. Excerpt(s): The present invention relates to the determination of the sequences of polymers immobilized to a substrate. In particular, one embodiment of the invention provides a method and apparatus for sequencing many nucleic acid sequences immobilized at distinct locations on a matrix surface. The principles and apparatus of the present invention may be used, for example, also in the determination of sequences of peptides, polypeptides, oligonucleotides, nucleic acids, oligosaccharides, phospholipids and other biological polymers. It is especially useful for determining the sequences of nucleic acids and proteins. The structure and function of biological molecules are closely interrelated. The structure of a biological polymer, typically a macromolecule, is generally determined by its monomer sequence. For this reason, biochemists historically have been interested in the sequence characterization of biological macromolecule polymers. With the advent of molecular biology, the relationship between a protein sequence and its corresponding encoding gene sequence is well understood. Thus, characterization of the sequence of a nucleic acid encoding a protein has become very important. Partly for this reason, the development of technologies providing the capability for sequencing enormous amounts of DNA has received great interest. Technologies for this capability are necessary for, for example, the successful completion of the human genome sequencing project. Structural characterization of biopolymers is very important for further progress in many areas of molecular and cell biology. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Serological assay for detection of antigens sequested within immune complexes Inventor(s): Brunner, Michael; (Columbus, NJ) Correspondence: Perkins Coie Llp; Post Office Box 1208; Seattle; WA; 98111-1208; US Patent Application Number: 20030134345 Date filed: July 17, 2002 Abstract: A method for detecting an antigen present in an immune complex comprises isolating an immune complex, which contains at least one antigen and at least one antibody specific for that antigen, from a sample, then incubating the immune complex under conditions effective to dissociate the immune complex and separate the antigen from the antibody. The dissociated antigen and antibody are then reassociated, and the reassociated antigen and antibody are separated from the solution, using a binding agent on a solid phase. The presence of the antigen is then detected and optionally quantified using an antigen-specific binding reaction. A second method is provided, in which the undissociated immune complexes are bound to a solid surface through an anti-IgM antibody, then are incubated with a biotinylated extract containing an antigen specific for the immune complex antibody. The presence of the biotin molecule is detected and optional quantified using a biotin-specific binding reaction. Excerpt(s): This application claims the priority of U.S. Provisional Patent Application Serial No. 60/305,933, filed Jul. 17, 2001, the entirety of which is hereby incorporated by reference. The present application is directed to serological assays for the diagnosis of infectious diseases in patients by detecting infectious disease-specific antigens, or the antibodies against such antigens, sequestered within immune complexes (ICs). The present application is also directed to serological assays for the diagnosis of autoimnmune diseases in patients by detecting autoimmune disease-specific antigens sequestered within ICs. Lyme disease is a potentially multi-system inflammatory disease in humans caused by the spirochete, Borrelia burgdorferi, which infects through the bite of spirochete-infected ticks. Lyme disease is often diagnosed clinically by the presence of bullseye-shaped erythema migrans (EM) rash. However, this "bullseye rash" occurs in only 60% to 80% of patients, and can be atypical in appearance. At about the same time that the rash develops, flu-like symptoms, such as headache, sore throat, stiff neck, fever, muscle aches, fatigue and general malaise, may appear. In some cases, the flu-like illness may appear without any rash. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Site specific binding system, imaging compositions and methods Inventor(s): Lanza, Gregory M.; (St. Louis, MO), Wickline, Samuel A.; (St. Louis, MO) Correspondence: Donald R. Holland; Harness, Dickey & Pierce, P.L.C.; Suite 400; 7700 Bonhomme Avenue; Saint Louis; MO; 63105; US Patent Application Number: 20020168320 Date filed: December 28, 2001 Abstract: A method for ligand-based binding of lipid encapsulated particles to molecular epitopes on a surface in vivo or in vitro comprises sequentially administering (a) a site specific ligand activated with a biotin activating agent; (b) an avidin activating agent; and (c) lipid encapsulated particles activated with a biotin activating agent, whereby the ligand is conjugated to the particles through an avidin-biotin interaction
Patents 191
and the resulting conjugate is bound to the molecular epitopes on such surface. The conjugate is effective for imaging by x-ray, ultrasound, magnetic resonance or positron emission tomography. Compositions for use in ultrasonic imaging of natural or synthetic surfaces and for enhancing the acoustic reflectivity thereof are also disclosed. Excerpt(s): This application is a divisional of application Ser. No. 09/404,963 which is a continuation-in-part of application Ser. No. 09/404,963, filed Sep. 24, 1999 which is a continuation-in-part of application Ser. No. 09/189,118, filed Nov. 9, 1998 which is a continuation of application Ser. No. 08/854,308, filed May 12, 1997 which is a divisional application of Ser. No. 08/488,743 filed Jun. 8, 1995, now U.S. Pat. No. 5,690,907 dated Nov. 25, 1997. This invention relates to a novel site specific binding system and novel compositions, and more particularly, to such a system and compositions which are useful in improved methods for ultrasonic imaging, drug or chemotherapeutic agent delivery, and diagnostic assays and detection systems. Heretofore, with respect to ultrasonic imaging, although ultrasonic contrast agents based upon "bubble" technology have been demonstrated to develop an acoustic impedance mismatch by virtue of gas encapsulated either in protein (Feinstein et al., J. Am. Coll. Cardiol. 1990; 16:316-324 and Keller et al., J. Am. Soc. Echo. 1989; 2:48-52), polysaccharide (Corday et al., J. Am. Coll. Cardiol. 1984; 3:978-85) biodegradable polymers (Schneider et al., Invest. Radiol., 1993; 27:134-139 and Bichon et al., European Patent Application No. 8908103 67.4: 1990) or lipids (D'Arrigo et al., J. Neurormag., 1991; 1: 134139; Simon et al., Invest. Radiol., 1992; 27:29-34; and Unger et al., Radiology 1992; 195:453-456), no experimental evidence of site-specific targeting of an acoustic contrast or imaging agent with resultant changes in the acoustic properties of the targeted tissue, surface or support are known. This lack of results has occurred despite numerous methods described in the literature for modifying such agents for targeting purposes, and the failure of past targeting approaches may be due to the chemical nature of the agents, production process limitations or particle instabilities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Streptavidin proteins Inventor(s): Cantor, Charles R.; (Berkeley, CA), Glazer, Alexander N.; (Orinda, CA), Sano, Takeshi; (Albany, CA) Correspondence: Richard Aron Osman; Science And Technology Law Group; 75 Denise Drive; Hillsborough; CA; 94010 Patent Application Number: 20030215922 Date filed: November 1, 2002 Abstract: Streptavidin-metallothionein chimeric proteins with biological recognition specificity in which the streptavidin moiety provides high affinity biotin binding and the metallothionein moiety provides a high affinity metal binding. The binding affinity of the streptavidin-metallothionein chimeric protein both for biotin and heavy metal ions allows specific incorporation into, conjugation with, or labelling of any biological material containing biotin with various heavy metal ions. Excerpt(s): This application is a continuing application of and claims priority under 35 U.S.C.sctn. 120 to U.S. Ser. No. 10/152,321, which claims priority to U.S. Ser. No. 07/780,717, filed Oct. 1, 1991, now U.S. Pat. No. 6,391,590, which are incorporated herein by reference. This invention concerns streptavidin-metallothionein chimeric proteins which possess biological recognition specificity. Recombinant streptavidin-
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metallothionein chimeric proteins containing various metal ions are molecules which have a great potential in preventive and therapeutic medicine in both humans and animals as well as for diagnostic use. While each individual molecule, i.e., streptavidin and metallothionein have been known and described previously, their composite molecule has never before been constructed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substrate preparation for chemical-species-specific binding Inventor(s): Myerholtz, Carl Alan; (Cupertino, CA), Tom-Moy, May; (San Carlos, CA) Correspondence: Agilent Technologies, INC.; Legal Department, 51upd; Intellectual Property Administration; P. O. Box 58043; Santa Clara; CA; 95052-8043; US Patent Application Number: 20020192718 Date filed: March 21, 2001 Abstract: A mass biosensor uses an intermediate avidin layer to facilitate binding of a biotinylated antibody to a measurement surface of the biosensor. The avidin layer can be added by the manufacturer of the biosensor, while the biotinylated layer can be added by the user. This two-phase method of chemically modifying the measurement surface significantly reduces the user time required to customize the measurement surface to render it capable of binding selected compounds. An organosilane coupling agent attached to the surface provides sites to which avidin is bound. Avidin acts as a universal receptor of biotinylated compounds with specific binding affinities. Biotinylated antibodies or other biotinylated compounds are added and bind to the immobilized avidin. Surface adsorption is reduced by washing the modified surface with biotin to block potential sites of weak bond formation, electrostatic and hydrophobic interactions. Excerpt(s): This Application is a continuation-in-part of U.S. patent application Ser. No. 251149, filed Sep. 29, 1988, which is hereby incorporated by reference. The present invention relates to analytical chemistry and, more particularly, to devices and methods which provide for selectively binding chemical species to a substrate. A major objective of the present invention is to provide for more convenient and effective chemical binding to a substrate used in the context of a mass biosensor. Preservation of the environment requires that the amounts of various pollutants on land and in water be monitored. Laboratories monitoring these pollutants are charged with measuring microquantities of many different chemicals. Mass biosensors provide a valuable tool in this application, as well as in medical and other applications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Target and method Inventor(s): Blackburn, Jonathan Michael; (Cambridge, GB), Koopmann, Jens-Oliver; (Cambridge, GB) Correspondence: Testa, Hurwitz & Thibeault, Llp; High Street Tower; 125 High Street; Boston; MA; 02110; US Patent Application Number: 20030180957 Date filed: December 20, 2002
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Abstract: The invention relates to a probe for the analysis of one or more proteins by laser desorption/ionisation mass spectrometry. The proteins include a tag, which in turn include a biotin group. The probe includes at least one surface including one or more of streptavidin, avidin or neutravidin molecules to bind the biotin group to the surface. The proteins can also carry a BCCP tag. The probe can form a protein array of two or more proteins at know locations on the surface of a chip. The invention also relates to methods of analysis by laser desorption/ionisation mass spectrometry using the probe. A scalable MALDI target volume sample volume loading kit and methods for its use are provided herein. Excerpt(s): This application claims priority to British applications, GB 0130747.9, filed Dec. 21, 2001, and GB 0216387.1, filed Jul. 15, 2002. The disclosures of each of these patent applications are incorporated by reference herein. Hutchins and Yip, 1993 introduced affinity-capture of proteins on MALDI-TOF sample carrier. [T. William Hutchens and Tai-Tung Yip, 1993 Rapid Communication in Mass Spectrometry, 7,576580.] This work presented a starting point for the development of affinity capture matrices on MALDI-TOF sample carriers. Hutchins and Yip captured lactoferrin with DNA-agarose from preterm infant urine. The agarose beads with affinity captured protein were loaded on the MALDI target, overlaid with energy absorbing matrix molecules and a good quality mass spectrum was acquired, whereas the unfractionated urine resulted in a poor mass spectrum due to signal suppression caused by salts and other proteins present in a complex sample as urine. The technology presented by Hutchins and Yip was slightly improved by Nelson et al., 1995 who describe a mass spectrometric immunoassay (MSIA) that can identify myotoxin and mojave toxin from blood samples. [Randall W. Nelson, Jennifer R. Krone, Allan R. Bieber, and Peter Williams. (1995) Analytical Chemistry 67, 1153-1158.] Affinity purified rabbit serum against the two toxins was conjugated to protein A agarose and the affinity matrix was then used to screen whole blood samples for the presence of myotoxin or mojave toxin. The major improvement described herein is the direct elution of the affinity-captured ligand onto the MALDI sample carrier. This enables to achieve higher mass accuracy in the MALDI process due to a homogenous flat layer of crystals compared to the heterogeneous surface preparation of Hutchins and Yip. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of dual conjugated labels in the elimination of serum interference in immunochromatographic assays Inventor(s): Schulman, Lloyd; (Osceola, IN), Sommer, Ronald; (Elkhart, IN), Wijesuriya, Daya C.; (Parkinson, AU) Correspondence: Jenkens & Gilchrist, P.C.; 225 West Washington; Suite 2600; Chicago; IL; 60606; US Patent Application Number: 20040014157 Date filed: July 19, 2002 Abstract: A method and device for carrying out immunoassays in which non analyte specific binding of heterophilic antibodies to a labeled antibody in a capture region produces an incorrect measure of the amount of an analyte attached to the antibody. Immunoglobulin from the same animal source as the labeled antibody is added to the sample fluid to prevent non-specific binding of the heterophilic antibodies in the capture region. One part of specific binding pair is added to said antibody or its label capable of binding to a second part of the binding pair immobilized in a control region
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downstream of said capture region for trapping the portion of the labeled anti-body which is not bound to the analyte. Preferably said binding pair is biotin/avidin or fluoroscein/anti-fluoroscein. Excerpt(s): This invention relates generally to testing of biological fluids such as blood, urine, and the like, more particularly to immunoassays which employ antibodies to detect antigens. Immunochromatographic strip formats have become increasingly popular for qualitative and semi-quantitative assays, particularly those which use visual detection schemes This type of immunoassay involves the application of a liquid test sample suspected of containing an analyte to an application zone of an immunochromatographic strip The presence of the analyte is typically indicated by a color which develops at a particular region of the strip For example, pregnancy tests in which the analyte is human chorionic gonadotropin (hCG). Usually, a test strip is comprised of a matrix material through which the test fluid, which may have the analyte suspended or dissolved therein, can flow by capillarity from the application zone to a detection zone where a detectable signal, or absence thereof, reveals the presence of the analyte Typically, the strip will include means for immunospecifically binding the analyte to be detected with its specific binding partner which bears a detectable label. In one such scheme, as disclosed in U.S. Pat. No. 4,446,232, the strip contains an enzyme labeled, mobile binding partner for the analyte which is in a zone downstream from the sample application zone. If analyte is present in the test sample, it will combine with its labeled binding partner to form a complex which can flow along the strip to a detection zone which contains a substrate for the enzyme label capable of providing a colored response in the presence of the enzyme label. The strip also contains a zone in which analyte has been immobilized, so that the labeled binding partner which does not combine with the analyte, due to absence of analyte in the sample, will be captured and thereby prevented from reaching the detection zone. There have been published various modifications of this technique, all of which involve some specific binding system in which the presence or absence of analyte in the test sample is determined by the detection or lack thereof of labeled binding partner in the detection zone. In U.S. Pat. No. 4,868,108 there is disclosed a similar scheme with the addition of an immobilized capture reagent for the enzyme labeled binding partner in the detection zone to concentrate the enzyme label and enhance its ability to react with the enzyme substrate to thereby render the assay more sensitive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Yeast with high biotin-productivity and the preparation method thereof Inventor(s): Shiuan, David; (Kaohsiung, TW) Correspondence: Bruce Londa; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20030104584 Date filed: January 2, 2001 Abstract: The invention discloses a yeast with high biotin-productivity and the preparation method thereof. The yeast is transformed by an integrated plasmid, which includes a biotin synthase gene, an assistant DNA sequence for the integration of the plasmid into a host genome, a promoter sequence, and a selection marker. Excerpt(s): The present invention relates to a method for the expression of biotin using edible yeast as a host, and more particularly, to a method for highly expressing biotin
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using edible yeast transformed by a genetically engineered plasmid. Biotin (2'-keto-3,4imidazolido-2-tetrahydrothiophene-n-valeric acid) was isolated from egg yolk by Kogl and Tonuis in 1936 and named as vitamin H. It is one of the essential vitamins for nutrition of animals, plants, and microorganisms, and very important as medicine or as a food additive. In general, biotin serves as a CO.sub.2 carrier for covalent binding in cells, and plays the role of coenzyme for carboxylase, decarboxylase, and transcarboxylase. Another birA gene whose product is the repressor of the operator is located at the 89 min on the E. coli genomic map. The repression of transcription of the operator requires the actions of the repressor and co-repressor (i.e. biotinyl-5'-adenylate) together with the operator. Further, the biotinyl-5'-adenylate is produced by the activation of biotin by the gene product of the birA (one function of which is bio repressor, and another is biotin holo enzyme synthetase). 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 biotin, 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 “biotin” (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 biotin. You can also use this procedure to view pending patent applications concerning biotin. 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 6. BOOKS ON BIOTIN Overview This chapter provides bibliographic book references relating to biotin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on biotin 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 “biotin” (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 biotin: •
Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline Source: Washington, DC: National Academy Press. 1998. 564 pp. Contact: Available from National Academy Press, 2101 Constitution Avenue, N.W., Lockbox 285, Washington, DC 20002 / e-mail:
[email protected] / Web site: http://www.nap.edu. $24.95; $19.96 (paperback) when ordered through the publisher's Web bookstore, plus $3.17 shipping and handling. Summary: This report is the second in a series that presents a comprehensive set of reference values for nutrient intakes for healthy populations. It establishes a set of reference values for the B vitamins and choline to replace the previously published recommended dietary allowances.
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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 “biotin” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “biotin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “biotin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Laboratory Guide to Biotin-Labeling in Biomolecule Analysis (Biomethods, Vol 7) by T. Meier (Editor), F. Fahrenholz (Editor); ISBN: 376435206X; http://www.amazon.com/exec/obidos/ASIN/376435206X/icongroupinterna
•
Avidin-Biotin Chemistry: A Handbook by M. Dean Savage; ISBN: 0935940111; http://www.amazon.com/exec/obidos/ASIN/0935940111/icongroupinterna
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Avidin-Biotin Technology : Volume 184: Avidin-Biotin Technology by John Abelson (Author), et al; ISBN: 0121820858; http://www.amazon.com/exec/obidos/ASIN/0121820858/icongroupinterna
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Biotin; ISBN: 089766289X; http://www.amazon.com/exec/obidos/ASIN/089766289X/icongroupinterna
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Biotin by Krishnamurti Dakshinamurti, Hemmige N. Bhagavan (Editor); ISBN: 0897662881; http://www.amazon.com/exec/obidos/ASIN/0897662881/icongroupinterna
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Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline by Institute of Medicine; ISBN: 0309064112; http://www.amazon.com/exec/obidos/ASIN/0309064112/icongroupinterna
Chapters on Biotin In order to find chapters that specifically relate to biotin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and biotin 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 “biotin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on biotin: •
Nutrition and the Professional Voice User Source: in Sataloff, R.T., ed. Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1997. p. 337-354. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619)
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238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $325.00 plus shipping and handling. ISBN: 1565937287. Summary: This chapter on nutrition and the professional voice user is from a book on the clinical care of the professional voice. Performers must understand why attention to their own nutritional status is important to their lives and livelihoods. Laryngeal and vocal health cannot be separated from general health and longevity. The authors stress that nutritional status is extremely important to the singer or actor who wants to be vital and energetic, maintain appropriate body weight, resist the colds and common maladies that often travel through an entire cast or choir. Stress and fatigue are endemic in performers, due in no small part to grueling audition, rehearsal, and performance schedules, working second and third jobs, intense competition, and self scrutiny. Without proper instruction and attention to nutrition and food choices, a performer's lifestyle demands can result in an unstable, inadequate nutritional status that invites illness. The authors discuss basic nutrition and dietary guidelines, recent research in nutrition, free radical pathology and antioxidant defenses, determining nutritional status, choosing supplements, nutrition fact food labels, food as medicine, vocal longevity and nutrition, and nutritional goals for performers. One extensive table summarizes the functions, RDA levels, and food sources of common nutrients, including fluids, carbohydrates, proteins, fatty acids, vitamins, biotin, folic acid, calcium, other minerals, and trace elements. 2 figures. 1 table. 118 references. •
Vitamin Metabolism and Requirements in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 415-477. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on vitamin metabolism and requirements is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors discuss several factors that may enhance the risk of abnormal vitamin levels in renal disease: decreased vitamin intake caused by anorexia, unpalatability of prescribed diets, or a dietary prescription that contains insufficient vitamins; increased degradation or endogenous clearance of vitamins from blood; elevated levels of vitamin binding proteins; losses of vitamins into dialysate; excretion of protein-bound vitamins by nephrotic patients; and interference of medicines with the absorption, excretion, and metabolism of vitamins. The authors review each of the common vitamins for its normal biochemistry and metabolism, the effect of renal disease and renal failure on these processes, and the clinical spectrum of vitamin disorders in these conditions. The authors propose guidelines concerning the needs for supplementation. Vitamins discussed are A, E, K, B1, B2, B6, B12, C, folates, niacin, biotin, and pantothenic acid. The authors conclude by calling for additional research to address vitamin supplementation in renal failure patients, particularly those on dialysis. 2 figures. 7 tables. 249 references. (AA-M).
•
Vitamins and Minerals Source: in Warshaw, H.S. and Webb, R. Diabetes Food and Nutrition Bible: A Complete Guide to Planning, Shopping, Cooking, and Eating. Alexandria, VA: American Diabetes Association. 2001. p. 7-14.
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Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $18.95 plus shipping and handling. ISBN: 158040037. Summary: This chapter on vitamins and minerals is from a book that offers a complete food and nutrition resource for people with diabetes. The book brings readers up to date on meal planning, carbohydrate counting, vitamins, minerals, and the best ways to prepare healthy delicious meals. In this chapter, the authors emphasize that vitamins are essential to the proper functioning of the body and they must be eaten in sufficient quantities to maintain health. The authors describe Recommended Dietary Allowances (RDAs) and several new categories of recommendations being developed under the heading of Dietary Reference Intakes (DRIs): Recommended Dietary Allowance, Adequate Intake (AI), Estimated Average Requirement (EAR), and Tolerable Upper Intake Level (UL). The authors then discuss water soluble vitamins, including vitamin B1 (thiamin), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), folate or folic acid, vitamin B12 (cobalamin), vitamin C, and biotin. The chapter then addresses the fat-soluble vitamins, including vitamin A, vitamin D, vitamin E, and vitamin K; and minerals, including calcium, iron, phosphorus, iodine, magnesium, zinc, selenium, copper, fluoride, and chromium. For each vitamin or mineral, the authors note good food sources for obtaining that nutrient. •
Trace Elements and Vitamins in Renal Disease Source: in Mitch, W.E., and Klahr, S., eds. Nutrition and the Kidney. 2nd ed. Boston, MA: Little, Brown and Company. 1993. p. 114-131. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:
[email protected]. Website: http://www.lrpub.com. PRICE: $94.95. ISBN: 0316575003. Summary: This chapter, from a medical textbook on nutrition and the kidney, reviews the metabolism, concentrations, and requirements of trace elements and vitamins in patients with chronic renal failure (CRF) prior to the onset of dialysis and during treatment with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Topics include the alteration of trace element metabolism in kidney failure, including aluminum, iron, zinc, copper, selenium, and ultra trace elements; and vitamins, including thiamine (B1), riboflavin (B2), pyridoxine (B6), cobalamin (B12), folic acid, biotin, niacin, pantothenic acid, ascorbic acid (vitamin C), retinol (vitamin A), and tocopherol (vitamin E). The authors briefly discuss recommendations for supplementation. 4 tables. 101 references.
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CHAPTER 7. PERIODICALS AND NEWS ON BIOTIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover biotin.
News Services and Press Releases One of the simplest ways of tracking press releases on biotin 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 “biotin” (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 biotin. 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 “biotin” (or synonyms). The following was recently listed in this archive for biotin: •
Biotin deficiency could be common in pregnancy Source: Reuters Health eLine Date: February 05, 2002
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “biotin” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “biotin” (or synonyms). If you know the name of a company that is relevant to biotin, 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 “biotin” (or synonyms).
Academic Periodicals covering Biotin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to biotin. In addition to these
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sources, you can search for articles covering biotin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “biotin” (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 16811 30 109 118 50 17118
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “biotin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Biotin In the following section, we will discuss databases and references which relate to the Genome Project and biotin. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “biotin” (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 biotin: •
Basal Ganglia Disease, Biotin-Responsive Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607483
•
Biotinidase Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=253260 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease,
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Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “biotin” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.
The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “biotin” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
22
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on biotin 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 biotin. 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 biotin. 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 “biotin”:
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Other guides Antioxidants http://www.nlm.nih.gov/medlineplus/antioxidants.html Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Vitamins and Minerals http://www.nlm.nih.gov/medlineplus/vitaminsandminerals.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on biotin. 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: •
Brittle Splitting Nails Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have brittle splitting nails or onychoschizia with information on this common problem. Brittle nails can be classified as dry and brittle or soft and brittle. Brittle nails are usually caused by repeated wetting and drying of the fingernails. An effective treatment is to apply lotions containing alpha hydroxy acids or lanolin to the nails after soaking them in water for 5 minutes and after getting the hands wet. Wearing gloves when performing household chores that involve getting the hands wet may also be helpful. Soft nails may be strengthened with nail polishes that contain nylon fibers. Nails should be shaped and filed with a very fine file, and the tips rounded in a gentle curve. Oral biotin is beneficial if taken for at least 6 months. 1 figure.
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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 biotin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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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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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to biotin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with biotin. 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 biotin. 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
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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 “biotin” (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 “biotin”. 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 “biotin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “biotin” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
24
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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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/
25
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BIOTIN 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] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] 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 renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] 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
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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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adduction: The rotation of an eye toward the midline (nasally). [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]
Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association
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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] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [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]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [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] 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] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] 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] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU]
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Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [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-helix: One of the secondary element of protein. [NIH] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group. [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 Motifs: Commonly observed structural components of proteins formed by
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simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amylase: An enzyme that helps the body digest starches. [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] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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]
Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a,
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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] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Angina: Chest pain that originates in 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] 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 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU]
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Antidepressant: A drug used to treat depression. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [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
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associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] 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 phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arenavirus: The only genus in the family Arenaviridae. It contains two groups LCM-Lassa complex viruses and Tacaribe complex viruses, which are distinguished by antigenic relationships and geographic distribution. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] 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] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes
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have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audition: The sense of 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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avidin: A specific protein in egg albumin that interacts with biotin to render it unavailable to mammals, thereby producing biotin deficiency. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH]
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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] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basal Metabolism: Heat production, or its measurement, of an organism at the lowest level of cell chemistry in an inactive, awake, fasting state. It may be determined directly by means of a calorimeter or indirectly by calculating the heat production from an analysis of the end products of oxidation within the organism or from the amount of oxygen utilized. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [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 composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of
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fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Sciences: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from biology, one of its subdivisions, concerned specifically with the origin and life processes of living organisms. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any
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living organism. [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] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotinylation: Incorporation of biotinyl groups into molecules. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose.
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[NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone marrow ablation: The destruction of bone marrow using radiation or drugs. [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 metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH]
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Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bumetanide: A sulfamyl diuretic. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] 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] Calorimeter: Measures the amounts of heat absorbed or given off by a solid, a liquid, or a gas. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
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Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [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]
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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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] 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] Catalyse: To speed up a chemical reaction. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catfish: Common name to express the order Siluriformes. This order contains many families and over 2,000 species, including venomous species. Heteropneustes and Plotosus genera have dangerous stings and are aggressive. Most species are passive stingers. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [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]
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Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular Structures: Components of a cell. [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] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Cervical intraepithelial neoplasia: CIN. A general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH]
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Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]
Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye
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between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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 Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [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] 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] Clathrin-Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the
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protein clathrin. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as endosomes. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the
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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] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Coliphages: Viruses whose host is Escherichia coli. [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] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the
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standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make 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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH]
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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]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] 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] Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of
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unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [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] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH]
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Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [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] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [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] Dengue Virus: A species of the genus Flavivirus which causes an acute febrile and sometimes hemorrhagic disease in man. Dengue is mosquito-borne and four serotypes are known. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] Deoxycytidine: A drug that protects healthy tissues from the toxic effects of anticancer drugs. [NIH]
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Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [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 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] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [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] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diet Records: Records of nutrient intake over a specific period of time, usually kept by the patient. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [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]
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Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dioxins: Chlorinated hydrocarbons containing heteroatoms that are present as contaminants of herbicides. Dioxins are carcinogenic, teratogenic, and mutagenic. They have been banned from use by the FDA. [NIH] Diploid: Having two sets of chromosomes. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [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 consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Dolichol: Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated. [NIH]
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Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Ice: A solid form of carbon dioxide used as a refrigerant. [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] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]
Dysgenic: Tending towards racial deterioration, in particular towards a loss of vigour and productiveness. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH]
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Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] 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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH]
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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] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [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]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH]
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Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [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] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] 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 Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1) activation by ions (activators); 2) activation by cofactors (coenzymes); and 3) conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. [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] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH]
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Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] 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] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte Deformability: Ability of erythrocytes to change shape as they pass through narrow spaces, such as the microvasculature. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] 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] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available
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and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] 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] Exotoxin: Toxic substance excreted by living bacterial cells. [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] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] 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] Fat: Total lipids including phospholipids. [NIH]
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Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fenbendazole: Antinematodal benzimidazole used in veterinary medicine. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] 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] 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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU]
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Flatus: Gas passed through the rectum. [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] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]
Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Antibody Technique: Test for tissue antigen using either a direct method by conjugation of antibody with fluorescent dye or an indirect method by formation of antigenantibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody. The tissue is then examined by fluorescence microscopy. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluoroimmunoassay: The use of fluorescence spectrometry to obtain quantitative results for the fluorescent antibody technique. One advantage over the other methods (e.g., radioimmunoassay) is its extreme sensitivity, with a detection limit on the order of tenths of microgram/liter. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [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] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods.
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[NIH]
Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [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] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosylceramides: Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy. [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 aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous
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capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] 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] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of
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heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] 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 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] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [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] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [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] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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 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
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glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [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] 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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [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
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supplement the action of estrogens. [NIH] Goniometer: An instrument for measuring angles, such as those of crystals and prisms. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Graphite: An allotropic form of carbon that is used in pencils, as a lubricant, and in matches and explosives. It is obtained by mining and its dust can cause lung irritation. [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] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Disorders: Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth. [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
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pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [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] 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] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of
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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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] 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]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody plants. [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] 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 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]
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
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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] 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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or
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T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrofluoric Acid: A solution of hydrogen fluoride in water. It is a colorless fuming liquid which can cause painful burns. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [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] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol
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and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU]
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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] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] 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] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in
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walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infectious Bursal Disease Virus: A species of Avibirnavirus causing severe inflammation of the bursa of Fabricius in chickens and other fowl. Transmission is thought to be through contaminated feed or water. Vaccines have been used with varying degrees of success. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [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 although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] 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]
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Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] 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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [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] 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]
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Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the
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dipolar ions are at a maximum. [NIH] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [NIH] Juniper: A slow growing coniferous evergreen tree or shrub, genus Juniperus. The Juniper is cultivated for its berries, which take up to three years to ripen. The resinous, sweetly flavored berries are borne only by the female juniper, and can be found in various stages of ripeness on the same plant. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH]
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Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lanolin: A yellow fat obtained from sheep's wool. It is used as an emollient, cosmetic, and pharmaceutic aid. [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] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limb Bud: A swelling on the trunk of the vertebrate embryo that becomes a limb. Limb bud cultures are used in developmental, organogenesis, morphogenesis, and cell differentiation studies. The limb bud of the chick embryo is most commonly used but mouse and rat limb buds are also used. [NIH]
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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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] 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] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [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 Extracts: Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] 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] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror
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through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytic Choriomeningitis Virus: The type species of arenavirus, part of the LCMLassa complex viruses, producing an inapparent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macronutrients: Nutrients in the diet that are the key sources of energy, namely protein, fat, and carbohydrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival,
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proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] 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]
Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH]
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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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane 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 Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] 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] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [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]
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Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] 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] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] 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] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] 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
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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]
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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [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, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH]
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Monotherapy: A therapy which uses only one drug. [EU] Monounsaturated fat: An unsaturated fat that is found primarily in plant foods, including olive and canola oils. [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] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple Carboxylase Deficiency: Abnormalities in carbohydrate and branched-chain amino acid catabolism that are responsive to biotin therapy. It may be due to deficiency of propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, biotinidase, or propionylCoA carboxylase, methylcrotonyl-CoA carboxylase, and pyruvate carboxylase. [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] Mung bean: A type of bean grown in warm climates. It is usually used for its seed and for bean sprouts. Mung bean may have anticancer effects. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]
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Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
Myelin: The fatty substance that covers and protects nerves. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] 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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nail Diseases: Diseases of the nail plate and tissues surrounding it. The concept is limited to primates. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Neisseria: A genus of gram-negative, aerobic, coccoid bacteria whose organisms are part of the normal flora of the oropharynx, nasopharynx, and genitourinary tract. Some species are primary pathogens for humans. [NIH]
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Neisseria gonorrhoeae: A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] 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] Neutralization: An act or process of neutralizing. [EU]
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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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nitrogenase: An enzyme system that catalyzes the fixing of nitrogen in soil bacteria and blue-green algae (cyanobacteria). EC 1.18.6.1. [NIH] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [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 Localization Signal: Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at nuclear pores. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH]
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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] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] 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] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oligoribonucleotides: A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties. [NIH]
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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] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin
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superfamily. [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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatin: A mammalian pancreatic extract composed of enzymes with protease, amylase and lipase activities. It is used as a digestant in pancreatic malfunction. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of
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uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitism: A) The mode of life of a parasite; b) The relationship between an organism (parasite) that derives benefits from, and at the expense of, another organism (host). [NIH] 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] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [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] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] 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
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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] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Mapping: Analysis of peptides generated from the digestion of a protein by a specific protease for the purpose of indentifing the protein or to look for polymorphisms. [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] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [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] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH]
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Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and
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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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet 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]
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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]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyploid: An organism with more than two chromosome sets in its vegetative cells. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvalent: Having more than one valence. [EU] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
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Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [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] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postprandial: Occurring after dinner, or after a meal; postcibal. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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 panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pregnenolone: Steroid hormone. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Proenzyme: Inactive form of an enzyme which can then be converted to the active form,
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usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes
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a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein-Energy Malnutrition: The lack of sufficient energy or protein to meet the body's metabolic demands, as a result of either an inadequate dietary intake of protein, intake of poor quality dietary protein, increased demands due to disease, or increased nutrient losses. [NIH]
Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH]
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Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyruvate Carboxylase: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of carbon dioxide to pyruvate. It is occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and lactic acidosis in infants. EC 6.4.1.1. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH]
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Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Fusion Proteins: Proteins that are the result of genetic engineering. A regulatory part or promoter of one or more genes is combined with a structural gene. The fusion protein is formed after transcription and translation of the fused gene. This type of fusion protein is used in the study of gene regulation or structure-activity relationships. They might also be used clinically as targeted toxins (immunotoxins). [NIH]
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Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH]
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Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH]
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Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Saturate: Means fatty acids without double bond. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol
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more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious
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bacterium or virus, as in virulence studies and the development of vaccines. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic
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number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silver Staining: The use of silver, usually silver nitrate, as a reagent for producing contrast or coloration in tissue specimens. [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU]
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Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]
Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincters: Any annular muscle closing an orifice. [NIH] Sphingomonas: A genus of gram-negative, aerobic, rod-shaped bacteria characterized by an outer membrane that contains glycosphingolipids but lacks lipopolysaccharide. They have the ability to degrade a broad range of substituted aromatic compounds. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH]
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Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptavidin: A 60kD extracellular protein of Streptomyces avidinii with four high-affinity biotin binding sites. Unlike AVIDIN, streptavidin has a near neutral isoelectric point and is free of carbohydrate side chains. [NIH] Streptomyces: A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the antibiotics of practical value. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of
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substrate on which the enzyme or catalytic molecule reacts. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules.
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Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU]
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Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thylakoids: Membranous cisternae of the chloroplast containing photosynthetic pigments, reaction centers, and the electron-transport chain. Each thylakoid consists of a flattened sac of membrane enclosing a narrow intra-thylakoid space (Lackie and Dow, Dictionary of Cell Biology, 2nd ed). Individual thylakoids are interconnected and tend to stack to form aggregates called grana. They are found in cyanobacteria and all plants. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH]
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Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is
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analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophic: Of or pertaining to nutrition. [EU] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH]
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Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tungsten: A metallic element with the atomic symbol W, atomic number 74, and atomic weight 183.85. It is used in many manufacturing applications, including increasing the hardness, toughness, and tensile strength of steel; manufacture of filaments for incandescent light bulbs; and in contact points for automotive and electrical apparatus. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond
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to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]
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Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays 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. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic
Dictionary 317
number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
319
INDEX A Abdomen, 227, 239, 254, 274, 278, 290, 292, 307, 308 Abdominal, 227, 263, 275, 290, 292, 301 Ablate, 12, 227 Ablation, 227 Acatalasia, 227, 242 Acceptor, 51, 119, 165, 180, 227, 278, 290, 297, 313 Acetylcholine, 227, 244, 287 Acidosis, 227, 299 Acoustic, 191, 227 Actin, 148, 227, 284, 285, 313 Actinin, 227, 255 Acute lymphoblastic leukemia, 55, 227 Acute lymphocytic leukemia, 227 Acute renal, 227, 268 Acyl, 50, 227 Adaptability, 227, 242, 243 Adaptation, 50, 227, 294 Adduct, 48, 228 Adduction, 48, 228 Adenine, 228, 299 Adenomatous Polyposis Coli, 96, 228 Adenosine, 43, 228, 240, 294 Adenovirus, 134, 145, 228 Adipose Tissue, 163, 228 Adjustment, 227, 228 Adjuvant, 23, 27, 93, 118, 228, 263 Adrenal Cortex, 228, 249, 297 Adrenal Glands, 228, 301 Adrenal Medulla, 228, 242, 258, 287 Adrenergic, 228, 254, 258, 309, 314 Adsorption, 60, 85, 98, 121, 131, 192, 228 Adsorptive, 228 Adverse Effect, 163, 228, 305 Aerobic, 160, 228, 282, 285, 286, 299, 307 Affinity Chromatography, 13, 49, 57, 183, 229 Agar, 229 Agarose, 73, 85, 188, 193, 229 Ageing, 130, 229 Agonist, 229, 254 Alanine, 12, 71, 229 Albumin, 35, 157, 229, 235, 289, 294, 310 Alertness, 229, 240 Alfalfa, 151, 229 Algorithms, 229, 238
Alimentary, 229, 252 Alkaline, 19, 26, 139, 227, 229, 231, 240, 290, 293 Alkaline Phosphatase, 19, 229 Alkaloid, 66, 229, 240, 246, 247, 303 Alkylation, 48, 229 Allergen, 175, 229 Allo, 230, 266 Allogeneic, 157, 230, 266 Allylamine, 230 Aloe, 150, 230 Alopecia, 122, 140, 230 Alpha Particles, 230, 299 Alpha-1, 230, 250 Alpha-helix, 230, 276 Alphavirus, 39, 230, 306 Alternative medicine, 202, 230 Alternative Splicing, 230, 298 Aluminum, 200, 230, 317 Alveolar Process, 230, 302 Amebiasis, 72, 230 Ameliorating, 10, 230 Amination, 13, 230 Amine, 33, 103, 153, 230, 269 Amino Acid Motifs, 7, 230 Amino Acid Sequence, 155, 158, 231, 232, 259, 263, 287 Amino Acid Substitution, 39, 148, 231 Ammonia, 230, 231, 314 Amphetamine, 231, 237 Amplification, 29, 37, 46, 60, 73, 78, 95, 97, 98, 155, 175, 186, 231 Ampulla, 231, 244, 259 Amylase, 231, 290 Amyloid, 22, 77, 231, 304 Anaerobic, 181, 231 Anal, 101, 142, 164, 231, 260 Analog, 38, 137, 156, 231, 261 Analogous, 10, 20, 25, 53, 131, 231, 254, 313 Analytes, 142, 154, 156, 161, 162, 169, 172, 231, 309 Anaphylactic, 176, 231 Anaphylatoxins, 231, 247 Anaphylaxis, 231, 232 Anatomical, 232, 256, 272, 304 Anemia, 20, 21, 23, 213, 232, 246, 261, 292 Anemic, 24, 232
320
Biotin
Angina, 166, 232 Angiogenesis, 232, 280 Animal model, 21, 36, 46, 56, 58, 165, 232 Anions, 229, 232, 275, 305 Annealing, 232, 295 Anomalies, 232, 310 Anorexia, 168, 199, 232, 263 Antagonism, 232, 240 Anterograde, 103, 232 Anthracycline, 232, 251 Antibacterial, 232, 307 Antibiotic, 123, 232, 251, 290, 291, 307 Anticoagulant, 185, 232, 298 Anticonvulsant, 232, 241, 315 Antidepressant, 33, 233 Antifungal, 103, 233 Antigen, 13, 15, 23, 27, 62, 64, 65, 68, 72, 77, 78, 87, 90, 97, 98, 134, 142, 144, 146, 156, 190, 228, 232, 233, 235, 247, 257, 261, 264, 269, 271, 272, 273, 280, 300, 309 Antigen-Antibody Complex, 233, 247, 261 Anti-infective, 233, 261, 270, 275 Anti-Infective Agents, 233, 261 Anti-inflammatory, 33, 233, 252, 264, 291 Antimetabolite, 233, 239, 252, 261 Antimicrobial, 233, 252 Antimitotic, 136, 233 Antineoplastic, 233, 239, 261 Antioxidant, 35, 180, 181, 199, 233, 234, 290 Antiserum, 233, 235 Antithrombotic, 185, 233 Antiviral, 7, 233, 239, 272, 274 Anuria, 233, 276 Anus, 231, 233, 239, 301 Aorta, 233, 301, 315 Apolipoproteins, 233, 278 Apoptosis, 29, 30, 108, 233, 242 Applicability, 9, 31, 56, 234 Aqueous, 139, 156, 169, 173, 188, 234, 236, 250, 256, 270, 277 Arachidonic Acid, 10, 234, 250, 255, 277, 297 Arenavirus, 7, 234, 279 Arginine, 55, 158, 171, 231, 234, 287 Aromatic, 22, 100, 131, 153, 234, 237, 282, 293, 307 Arrhythmia, 151, 234 Arterial, 230, 234, 244, 271, 298, 310 Arteries, 233, 234, 238, 249, 278, 282, 285, 311, 314 Arterioles, 234, 238, 240, 285
Arteriosclerosis, 234, 271 Arthroscopy, 5, 234 Articular, 5, 234, 276, 289 Ascorbic Acid, 120, 157, 159, 181, 200, 234, 270 Aseptic, 234, 279, 289 Aspartate, 158, 234 Aspartic, 55, 234, 245, 256 Aspartic Acid, 55, 234, 245 Assay, 9, 29, 30, 37, 39, 60, 63, 68, 76, 78, 81, 91, 98, 107, 114, 116, 118, 119, 143, 163, 164, 168, 169, 174, 188, 190, 194, 234, 271, 300, 314 Astrocytes, 33, 234, 283 Asymptomatic, 9, 227, 230, 235 Ataxia, 83, 212, 213, 235, 310 Atopic, 140, 235 Atrophy, 212, 213, 235, 286 Attenuated, 235, 253 Atypical, 190, 235 Audition, 199, 235 Autoantibodies, 88, 235 Autoantigens, 235 Autoimmune disease, 190, 235, 284 Autoimmunity, 27, 235 Autologous, 157, 235 Autonomic, 227, 235, 287, 292 Autoradiography, 18, 77, 235 Avidity, 46, 96, 235 Axonal, 10, 235 Axons, 10, 114, 235, 251 B Bacillus, 62, 63, 64, 66, 67, 68, 74, 101, 116, 132, 139, 176, 187, 235, 250 Bacterial Infections, 146, 235, 243 Bacterial Physiology, 228, 235 Bactericidal, 236, 258 Bacteriophage, 31, 53, 75, 138, 236, 312 Bacteriophage lambda, 138, 236 Bacterium, 139, 171, 176, 236, 248, 268, 305 Basal Ganglia, 212, 235, 236, 262 Basal Ganglia Diseases, 235, 236 Basal Metabolism, 150, 236 Base, 65, 133, 186, 228, 236, 250, 251, 252, 259, 262, 263, 276, 277, 292, 293, 295, 310, 314 Base Sequence, 186, 236, 250, 262, 263 Basement Membrane, 236, 259, 277 Benign, 236, 262, 267, 279, 286, 290, 300, 316 Beta carotene, 151, 236 Beta Rays, 236, 255
Index 321
Beta-Galactosidase, 236, 262 Beta-pleated, 231, 236 Bilateral, 86, 236 Bile, 6, 150, 236, 237, 269, 278, 307 Bile Acids, 6, 236, 237, 307 Bile Acids and Salts, 236, 237 Biliary, 237, 244 Bilirubin, 229, 237 Binding agent, 130, 156, 163, 190, 237 Binding Sites, 18, 155, 237, 308 Bioassay, 183, 237 Biochemical reactions, 50, 237, 311 Bioengineering, 21, 51, 100, 101, 177, 208, 237 Biogenic Amines, 33, 237 Biological response modifier, 237, 274 Biological Sciences, 100, 101, 148, 237 Biological therapy, 237, 266 Biological Transport, 237, 252 Biomedical Engineering, 13, 237 Biomolecular, 51, 54, 77, 81, 84, 89, 156, 183, 237, 309 Biophysics, 26, 38, 52, 116, 237 Biopolymers, 25, 178, 189, 237 Biotechnology, 8, 59, 75, 85, 101, 130, 137, 179, 202, 209, 211, 212, 213, 214, 237, 238 Bioterrorism, 7, 238 Biotic, 141, 238 Biotransformation, 22, 238 Biphasic, 152, 153, 238 Bivalent, 238, 282 Bladder, 238, 272, 284, 297, 314 Blood Coagulation, 185, 238, 240, 311 Blood Coagulation Factors, 238 Blood Glucose, 238, 267, 271, 274 Blood Platelets, 238, 280, 305, 311 Blood pressure, 238, 241, 244, 271, 283, 292, 306 Blood vessel, 34, 232, 238, 241, 243, 257, 264, 268, 275, 279, 281, 292, 306, 308, 310, 311, 315 Blood-Brain Barrier, 34, 56, 78, 238 Blot, 64, 65, 98, 238, 271, 288 Blotting, Western, 239, 271 Body Fluids, 108, 146, 162, 239, 254, 306 Bone marrow ablation, 24, 239 Bone Marrow Cells, 49, 239, 280 Bone metastases, 239, 300 Bone Remodeling, 47, 239 Bone Resorption, 239 Bowel, 3, 231, 239, 274, 292, 308 Bowel Movement, 239, 308
Brachytherapy, 239, 274, 275, 300, 316 Bradykinin, 239, 287, 294 Branch, 223, 239, 255, 279, 291, 299, 301, 306, 310 Breakdown, 160, 239, 252, 263, 289 Breeding, 70, 139, 182, 239 Bromine, 159, 239 Bromodeoxyuridine, 37, 239 Bronchial, 240, 269 Buccal, 240, 308 Bumetanide, 32, 240 Burns, 135, 240, 270 Burns, Electric, 240 C Caffeine, 4, 240, 299 Callus, 240, 256 Calmodulin, 16, 240 Calorimeter, 236, 240 Camptothecin, 49, 85, 113, 240 Candidiasis, 65, 122, 240 Candidosis, 240 Capillary, 58, 66, 162, 239, 240, 315 Capsid, 132, 240, 315 Capsular, 73, 146, 241 Capsules, 241, 263 Carbamazepine, 117, 124, 241 Carbohydrate, 97, 135, 142, 160, 200, 241, 264, 265, 284, 288, 295, 304, 308 Carbon Dioxide, 241, 250, 251, 254, 260, 294, 299, 302 Carboxy, 128, 146, 241 Carcinogen, 186, 228, 241 Carcinogenic, 241, 253, 273, 289, 297, 307, 314 Carcinoma, 85, 113, 241 Cardiac, 151, 230, 240, 241, 255, 256, 258, 265, 285, 307 Cardiovascular, 43, 166, 168, 182, 231, 241, 277, 305 Cardiovascular disease, 43, 168, 241 Cardiovascular System, 182, 241 Carnitine, 108, 135, 241 Carotene, 180, 181, 236, 241, 302 Carotenoids, 137, 167, 236, 241 Carotid Body, 241, 244 Carrier Proteins, 241, 294, 300 Carrier State, 230, 241 Case report, 92, 241, 242, 246 Case series, 242, 246 Caspase, 29, 242 Catabolism, 10, 33, 38, 111, 242, 284, 314 Catalase, 181, 227, 242
322
Biotin
Catalyse, 163, 242 Catecholamine, 242, 254 Catfish, 110, 242 Cathode, 236, 242, 255 Cations, 242, 275 Cause of Death, 43, 166, 182, 242 Cell Adhesion, 158, 242 Cell Count, 22, 242, 292 Cell Cycle, 25, 80, 100, 242, 315 Cell Death, 29, 30, 165, 233, 242, 264, 285 Cell Differentiation, 157, 242, 277, 305 Cell Division, 212, 235, 242, 243, 266, 281, 282, 283, 294, 297 Cell Extracts, 12, 242 Cell Fusion, 19, 20, 242 Cell membrane, 10, 20, 39, 56, 170, 237, 241, 242, 252, 263, 281, 293, 306, 316 Cell proliferation, 9, 16, 24, 29, 55, 82, 108, 234, 243, 305 Cell Respiration, 243, 282, 302 Cell Size, 243, 261 Cell Survival, 21, 22, 243, 266 Cellobiose, 243 Cellular Structures, 243, 283 Cellulose, 179, 243, 262, 294 Central Nervous System Infections, 243, 267 Centrifugation, 170, 243 Ceramide, 243, 262 Cerebellar, 235, 243, 301 Cerebral, 166, 235, 236, 238, 243, 258, 259, 299 Cerebrospinal, 34, 82, 84, 243 Cerebrospinal fluid, 34, 82, 84, 243 Cerebrovascular, 236, 241, 243, 310 Cerebrum, 243, 313 Cervical, 37, 82, 103, 243 Cervical intraepithelial neoplasia, 82, 243 Cervix, 243, 302 Chelation, 77, 98, 121, 244 Chemokines, 81, 145, 244 Chemoreceptor, 16, 244 Chemotactic Factors, 244, 247 Chemotaxis, 17, 244 Chemotherapeutics, 31, 244 Chemotherapy, 14, 30, 46, 85, 113, 171, 244 Chimeras, 50, 244 Chimeric Proteins, 132, 155, 191, 244 Chlorine, 150, 171, 244 Chlorophyll, 244, 250, 262 Chloroplasts, 11, 244, 250 Cholecalciferol, 180, 244
Cholera, 15, 244, 305 Cholestasis, 7, 244 Cholesterol, 14, 39, 54, 111, 148, 166, 236, 237, 244, 245, 249, 254, 270, 278, 303, 307 Cholesterol Esters, 244, 278 Choline, 149, 197, 198, 244, 293 Choroid, 244, 302 Chromatin, 27, 233, 245 Chromic, 166, 245 Chromium, 4, 114, 135, 137, 149, 150, 165, 167, 181, 200, 245 Chromosomal, 88, 167, 231, 245, 294, 302 Chromosome, 69, 167, 245, 248, 267, 278, 295, 313, 314 Chromosome Aberrations, 167, 245 Chromosome Abnormalities, 167, 245 Chronic Disease, 149, 245 Chronic Fatigue Syndrome, 135, 245 Chronic granulocytic leukemia, 245 Chronic myelogenous leukemia, 167, 245 Chronic renal, 108, 200, 245, 295 Chylomicrons, 245, 278 Chymopapain, 245, 290 Circadian, 66, 245 CIS, 50, 245, 272, 302 Citrus, 234, 245 Clamp, 16, 245 Clathrin, 15, 145, 245, 246, 257 Clathrin-Coated Vesicles, 145, 245 Clear cell carcinoma, 246, 252 Cleave, 38, 153, 246 Clinical Medicine, 119, 246, 296 Clinical study, 21, 141, 246 Clinical trial, 5, 13, 20, 30, 46, 209, 246, 249, 250, 298, 300 Clone, 10, 36, 45, 246 Cloning, 19, 35, 63, 64, 70, 91, 138, 238, 246, 277 Coagulation, 238, 246, 268, 294, 311 Coated Vesicles, 245, 246, 257 Cobalt, 73, 159, 246 Coca, 246 Cocaine, 28, 246 Cod Liver Oil, 246, 256 Coenzyme, 22, 67, 70, 71, 73, 74, 91, 108, 135, 147, 195, 234, 246, 287 Cofactor, 38, 40, 51, 53, 70, 184, 246, 287, 298, 311 Cognition, 34, 76, 247 Colchicine, 118, 247, 313 Coliphages, 236, 247
Index 323
Collagen, 29, 148, 236, 247, 259, 260, 263, 280, 294, 297 Collapse, 51, 232, 239, 247 Colloidal, 111, 114, 119, 168, 174, 229, 247, 255, 292, 305 Combinatorial, 7, 96, 247 Complement, 18, 33, 58, 113, 231, 247, 263, 280, 294 Complementary and alternative medicine, 107, 125, 247 Complementary medicine, 107, 247 Computational Biology, 209, 211, 248 Cones, 248, 302 Confusion, 248, 314 Congestion, 248, 258 Congestive heart failure, 166, 168, 248 Conjugation, 19, 47, 57, 77, 98, 121, 155, 163, 173, 191, 238, 248, 261 Connective Tissue, 87, 148, 234, 239, 247, 248, 260, 262, 263, 279, 281, 298, 308 Connective Tissue Cells, 248 Consciousness, 248, 251, 253 Conserved Sequence, 231, 248 Constipation, 248, 262, 275 Constriction, 11, 248, 275 Consultation, 4, 18, 248 Consumption, 135, 248, 252, 263, 288, 302 Contraindications, ii, 248 Control group, 4, 249 Controlled study, 10, 249 Coordination, 249, 284 Cornea, 249, 317 Coronary, 166, 241, 249, 282, 285 Coronary Arteriosclerosis, 249, 285 Coronary heart disease, 166, 241, 249 Coronary Thrombosis, 249, 282, 285 Corpus, 249, 292, 297 Corpus Luteum, 249, 297 Corpuscle, 249, 258 Cortex, 235, 249, 257, 259, 301 Cortical, 29, 34, 48, 249, 304, 310 Cortisol, 229, 249 Cortisone, 249, 252 Cranial, 249, 267, 292 Craniocerebral Trauma, 236, 249, 267, 310 Cryostat, 18, 249 Cultured cells, 8, 55, 249 Curative, 14, 249, 287, 303, 310 Cutaneous, 83, 110, 240, 249 Cyanobacteria, 249, 287, 311 Cyclic, 240, 250, 266, 287, 297 Cyclodextrins, 130, 136, 250
Cyclooxygenase Inhibitors, 10, 250 Cyclosporine, 250, 272 Cysteine, 28, 47, 48, 64, 159, 181, 244, 245, 250, 256, 309 Cystine, 159, 250 Cytochrome, 67, 250 Cytokine, 5, 9, 16, 49, 89, 114, 144, 250 Cytoplasm, 181, 233, 242, 250, 255, 266, 282, 285, 303, 310, 315 Cytoskeletal Proteins, 10, 245, 250, 255 Cytoskeleton, 250 Cytotoxic, 23, 58, 250, 300, 305 Cytotoxicity, 30, 73, 230, 251 D Dairy Products, 251, 303 Databases, Bibliographic, 209, 251 Daunorubicin, 15, 251 De novo, 55, 251 Deamination, 251, 283, 314 Decarboxylation, 147, 184, 237, 251, 269 Defense Mechanisms, 162, 251 Degenerative, 251, 268, 289 Dehydration, 20, 21, 32, 51, 244, 251 Deletion, 34, 41, 64, 233, 251 Dementia, 33, 122, 123, 251 Denaturation, 21, 251, 295 Dendrites, 251, 286 Dendritic, 251, 281, 307 Dengue Virus, 84, 251 Density, 22, 121, 133, 142, 166, 170, 243, 251, 254, 261, 278, 289, 295 Dentate Gyrus, 251, 268 Deoxycytidine, 59, 251 Deoxyribonucleotides, 252, 288 Deoxyuridine, 34, 252 Depolarization, 252, 305 Dermatitis, 115, 122, 123, 140, 252 DES, 26, 102, 103, 141, 172, 193, 231, 252 Detergents, 4, 147, 252 Deuterium, 31, 252, 270 Developed Countries, 252, 261 Dexamethasone, 157, 252 Diabetes Mellitus, 55, 123, 252, 264, 267 Diagnostic procedure, 129, 202, 252, 293, 305 Dialysate, 199, 252 Dialyzer, 252, 267 Diarrhea, 71, 230, 252, 262, 275 Diastolic, 252, 271 Diet Records, 4, 252 Dietary Fats, 252, 278 Dietary Fiber, 4, 252
324
Biotin
Diffusion, 134, 188, 237, 252, 253, 273 Digestion, 38, 113, 128, 151, 229, 236, 237, 239, 252, 274, 278, 292, 308 Digoxigenin, 37, 108, 109, 138, 253 Dihydropyridines, 33, 253 Dihydrotestosterone, 253, 301 Dihydroxy, 253, 258 Dilatation, 253, 296 Dilution, 169, 253 Dimerization, 101, 253 Dimethyl, 53, 253 Dioxins, 171, 253 Diploid, 253, 294, 313 Dipyridamole, 22, 253 Disinfectant, 253, 258 Disposition, 24, 253 Dissection, 26, 28, 52, 253 Dissociation, 25, 59, 101, 134, 137, 145, 228, 253, 275 Dissociative Disorders, 253 Distal, 235, 253, 255, 276, 299 Diuresis, 240, 253 Diuretic, 240, 253 Docetaxel, 113, 253 Dolichol, 42, 253 Domesticated, 254, 267 Dopamine, 33, 114, 231, 246, 254, 283, 293 Dorsal, 103, 254, 296 Dorsum, 254, 262 Drug Delivery Systems, 54, 156, 254 Drug Design, 7, 156, 254 Drug Interactions, 254 Drug Tolerance, 254, 312 Dry Ice, 18, 254 Duct, 231, 254, 303 Duodenum, 236, 254, 308 Dyes, 50, 231, 254, 261, 262, 293 Dysentery, 230, 254 Dysgenic, 50, 254 Dyslipidemia, 165, 254 Dysplasia, 213, 254 Dystrophin, 42, 255, 284 Dystrophy, 123, 212, 255 E Effector, 103, 173, 227, 247, 255, 286 Efficacy, 6, 46, 85, 113, 140, 254, 255 Egg Yolk, 195, 255 Eicosanoids, 250, 255 Elastin, 247, 255, 259 Elective, 73, 95, 255 Electrode, 119, 242, 255 Electrolyte, 255, 276, 296, 306
Electron microscope, 174, 255 Electrons, 148, 233, 236, 242, 255, 275, 290, 299, 300, 309 Electrophoresis, 8, 45, 58, 66, 96, 161, 255 Electrophysiological, 16, 40, 255 Elementary Particles, 255, 287, 298 Embryo, 34, 44, 60, 242, 255, 256, 277, 314 Embryogenesis, 44, 256 Emodin, 230, 256 Emollient, 4, 256, 265, 277, 288 Emulsion, 188, 235, 256, 260 Enamel, 256, 276 Encapsulated, 136, 188, 190, 191, 256 Encephalitis, 256 Encephalomyelitis, 56, 256 Endemic, 199, 244, 256, 307 Endocarditis, 118, 240, 256 Endocardium, 256 Endocytosis, 15, 56, 89, 97, 115, 145, 256 Endometrial, 256 Endometriosis, 18, 92, 256 Endometrium, 256, 281 Endopeptidases, 256, 298 Endosomes, 47, 246, 256, 257 Endothelial cell, 29, 56, 78, 165, 238, 256, 257, 311 Endothelium, 257, 287 Endothelium-derived, 257, 287 Endotoxin, 127, 257, 314 End-stage renal, 4, 245, 257, 295 Energetic, 199, 257 Enhancer, 57, 178, 257 Entorhinal Cortex, 257, 269 Environmental Exposure, 257, 289 Environmental Health, 208, 210, 257 Enzyme Activation, 14, 38, 257 Enzyme Inhibitors, 257, 294 Enzyme-Linked Immunosorbent Assay, 65, 68, 72, 73, 75, 84, 87, 257 Epidemic, 65, 257, 307 Epidermal, 77, 100, 257, 276, 281, 316 Epidermal Growth Factor, 77, 100, 257 Epidermis, 257, 258, 276, 296 Epinephrine, 228, 237, 254, 258, 287, 314 Epithelial, 12, 57, 79, 132, 141, 237, 257, 258, 277, 290 Epithelial Cells, 57, 79, 257, 258, 277 Epithelium, 12, 24, 57, 62, 92, 117, 236, 257, 258, 290, 317 Epitope, 9, 68, 145, 146, 156, 258 Erythema, 190, 258 Erythroblasts, 258
Index 325
Erythrocyte Deformability, 20, 258 Erythrocyte Membrane, 20, 258, 307 Erythrocytes, 21, 76, 77, 113, 232, 239, 258, 268, 301 Erythroid Progenitor Cells, 24, 258 Erythropoiesis, 24, 258 Erythropoietin, 23, 258 Essential Tremor, 212, 258 Estrogen, 181, 258 Ethanol, 55, 153, 258, 260 Ethylene Glycol, 13, 77, 85, 103, 113, 258 Eukaryotic Cells, 133, 250, 259, 272, 288, 289, 314 Evoke, 259, 307 Excipients, 259, 261, 293 Excitation, 50, 156, 178, 244, 259, 261 Excrete, 233, 259, 276 Exogenous, 35, 167, 228, 238, 259 Exon, 16, 230, 259 Exotoxin, 15, 62, 259 External-beam radiation, 259, 275, 300, 316 Extracellular, 9, 18, 25, 34, 36, 43, 47, 75, 87, 231, 234, 248, 256, 259, 260, 280, 306, 308 Extracellular Matrix, 248, 259, 260, 280 Extracellular Matrix Proteins, 259, 280 Extracorporeal, 98, 121, 162, 259 Extraction, 59, 162, 259 Extrapyramidal, 254, 259 Eye Infections, 228, 259 F Fallopian Tubes, 259, 302 Family Planning, 209, 259 Fat, 4, 112, 128, 135, 168, 200, 228, 234, 236, 237, 239, 241, 243, 249, 259, 277, 278, 279, 284, 288, 295, 303, 306, 309, 310, 313 Fatigue, 190, 199, 245, 260, 267 Fatty acids, 109, 115, 148, 163, 199, 229, 255, 260, 265, 293, 297, 303 Febrile, 251, 260 Fecal Incontinence, 3, 260, 272 Feces, 248, 260, 308 Fenbendazole, 159, 260 Fermentation, 132, 139, 140, 151, 152, 177, 260, 262 Ferritin, 66, 260 Fetus, 258, 260, 294, 296, 314 Fibrin, 238, 260, 311 Fibrinogen, 107, 260, 294, 311 Fibroblasts, 44, 114, 165, 248, 260, 274 Fibronectin, 29, 260
Fibrosis, 40, 213, 230, 260, 303, 304 Filtration, 49, 260, 276 Fixation, 11, 14, 19, 260 Flatus, 260, 261, 263 Flavodoxin, 38, 187, 261 Flavoring Agents, 261, 293 Flow Cytometry, 9, 15, 43, 70, 95, 108, 188, 261 Fluorescence, 18, 51, 67, 69, 87, 90, 91, 93, 96, 156, 174, 178, 261 Fluorescent Antibody Technique, 261 Fluorescent Dyes, 261 Fluoroimmunoassay, 64, 93, 261 Fluorouracil, 253, 261 Folate, 4, 25, 41, 69, 84, 197, 198, 200, 252, 261 Fold, 24, 30, 184, 261 Folic Acid, 105, 149, 150, 159, 167, 181, 182, 199, 200, 261 Food Additives, 132, 261 Food Coloring Agents, 261, 262 Food Preservatives, 261, 262 Forearm, 176, 238, 262 Fovea, 260, 262 Fractionation, 175, 262 Frameshift, 262, 314 Frameshift Mutation, 262, 314 Fructose, 262, 275 Functional Disorders, 140, 262 Fungi, 152, 233, 248, 259, 262, 266, 282, 316 Fungus, 4, 240, 262 G Galactosylceramides, 97, 262 Gamma Rays, 262, 300 Ganglia, 227, 236, 262, 286, 292 Ganglion, 262, 317 Ganglioside, 15, 263 Gangrenous, 263, 305 Gap Junctions, 263, 309 Gas, 191, 231, 240, 241, 244, 252, 261, 262, 263, 270, 275, 287, 288, 309 Gastric, 241, 257, 263, 269, 270 Gastrin, 263, 269 Gastroenteritis, 239, 263 Gastrointestinal, 57, 79, 168, 239, 258, 263, 277, 305, 308 Gastrointestinal tract, 57, 258, 263, 277, 305 Gelatin, 29, 84, 263, 265, 309, 311 Gels, 84, 263 Gene Expression, 29, 43, 48, 49, 58, 130, 161, 213, 263
326
Biotin
Gene Silencing, 49, 263 Genetic Code, 263, 288 Genetic Engineering, 139, 155, 176, 186, 238, 246, 263, 300 Genetic testing, 263, 295 Genetics, 16, 41, 67, 83, 86, 91, 94, 95, 248, 263, 283 Genital, 65, 132, 246, 264 Genitourinary, 264, 285 Genomics, 13, 31, 88, 264 Genotype, 82, 264, 293 Germ Cells, 264, 281, 289 Gestation, 9, 264, 294 Giant Cells, 264, 303 Ginger, 150, 264 Gland, 88, 228, 249, 264, 279, 280, 290, 291, 297, 304, 307, 308, 311 Glioma, 93, 94, 118, 264 Glomerular, 28, 264, 275, 276, 301 Glomeruli, 264 Glomerulosclerosis, 28, 264 Glomerulus, 264, 276 Glucans, 250, 264 Glucocorticoid, 252, 264 Glucokinase, 114, 264 Gluconeogenesis, 38, 264 Glucose, 61, 82, 85, 97, 109, 114, 117, 212, 234, 238, 243, 245, 250, 252, 264, 265, 267, 273, 274, 303 Glucose tolerance, 117, 264 Glucose Tolerance Test, 117, 264, 265 Glucuronic Acid, 265, 268 Glutamate, 16, 49, 265 Glutamic Acid, 261, 265, 268, 297 Glutathione Peroxidase, 181, 265, 304 Glycerol, 163, 265, 293 Glycerophospholipids, 265, 293 Glycine, 158, 237, 265, 305 Glycogen, 115, 135, 265 Glycogen Storage Disease, 115, 265 Glycols, 265, 270 Glycoprotein, 14, 55, 96, 119, 258, 260, 264, 265, 266, 277, 280, 310, 311, 314 Glycosaminoglycans, 259, 265, 298 Glycosidic, 25, 243, 262, 265, 289 Glycosylation, 42, 265 Gonadal, 265, 307 Gonadotropin, 194, 265 Goniometer, 22, 266 Gonorrhea, 266, 286 Gout, 247, 266 Governing Board, 266, 296
Gp120, 20, 23, 266 Grade, 82, 266 Graft, 174, 266, 269, 272, 299 Graft Rejection, 266, 272 Graft-versus-host disease, 266, 299 Gram-negative, 146, 250, 266, 285, 286, 299, 307 Gram-positive, 266, 285 Granule, 251, 266, 303 Granulocytes, 266, 285, 305, 316 Graphite, 184, 266 Grasses, 261, 266, 268 Gravidity, 266, 291 Growth Disorders, 141, 266 Growth factors, 39, 145, 266 Guanylate Cyclase, 266, 287 Guinea Pigs, 19, 267, 279 H Habitat, 159, 267, 285 Half-Life, 186, 267 Haploid, 267, 294 Haptens, 37, 153, 228, 267, 300 Headache, 190, 240, 267, 273 Headache Disorders, 267 Health Promotion, 149, 267 Heart attack, 43, 241, 267 Heart failure, 267 Helminths, 267, 273 Hematology, 41, 267, 293 Hematopoiesis, 26, 267 Hematopoietic Stem Cells, 26, 134, 267 Heme, 237, 250, 267, 295 Hemodialysis, 4, 117, 200, 252, 267, 276 Hemoglobin, 21, 22, 87, 232, 258, 267, 268, 277 Hemoglobin A, 21, 87, 268 Hemoglobin C, 22, 232, 268 Hemoglobinuria, 212, 268 Hemolysis, 258, 268 Hemolytic, 20, 268 Hemorrhage, 249, 267, 268, 308 Hemostasis, 49, 268, 305 Heparin, 185, 268 Hepatic, 114, 150, 229, 264, 268, 283, 295, 296 Hepatitis, 23, 65, 268 Hepatocyte, 6, 55, 244, 268 Herbicides, 253, 268 Hereditary, 266, 268, 286, 292, 302 Heredity, 86, 263, 264, 268 Herpes, 62, 65, 72, 75, 268 Herpes Zoster, 268
Index 327
Heterogeneity, 25, 229, 268 Hippocampus, 34, 251, 268, 308 Histamine, 93, 231, 237, 269 Histidine, 269 Histology, 18, 269, 291 Homeostasis, 11, 25, 85, 100, 143, 239, 269 Homogeneous, 163, 175, 269 Homologous, 158, 238, 250, 269, 284, 309, 310, 313 Hormonal, 25, 163, 235, 269, 316 Hormone, 37, 143, 155, 181, 230, 237, 249, 252, 255, 258, 263, 269, 274, 275, 281, 291, 294, 296, 297, 305, 310, 311, 316 Hormone Replacement Therapy, 181, 182, 269 Horseradish Peroxidase, 111, 257, 269 Human Development, 159, 208, 269 Human Genome Project, 36, 58, 214, 269 Human growth hormone, 155, 269 Human papillomavirus, 82, 269 Humoral, 23, 266, 269 Humour, 269 Hybrid, 7, 50, 186, 246, 269, 288 Hybridomas, 19, 269, 274 Hydration, 21, 32, 270 Hydrochloric Acid, 160, 270 Hydrofluoric Acid, 270, 306 Hydrogel, 131, 270 Hydrogen Bonding, 137, 270, 288 Hydrogen Peroxide, 17, 165, 181, 242, 265, 270, 278 Hydrolases, 256, 270, 279 Hydrolysis, 163, 234, 236, 238, 243, 253, 270, 293, 295, 298 Hydrophilic, 147, 169, 252, 270 Hydrophobic, 33, 44, 147, 169, 192, 252, 265, 270, 278 Hydroxides, 270 Hydroxy Acids, 216, 270 Hydroxyl Radical, 20, 270 Hydroxylysine, 247, 270 Hydroxyproline, 247, 270 Hypercalcemia, 143, 270 Hypercholesterolemia, 166, 254, 270 Hyperglycemia, 165, 166, 270 Hyperlipidemia, 135, 254, 270 Hyperlipoproteinemia, 270, 271 Hypersensitivity, 229, 232, 271, 277 Hypertension, 135, 166, 168, 241, 267, 271 Hyperthyroidism, 168, 271 Hypertriglyceridemia, 135, 254, 271 Hypoglycemic, 57, 271
Hysterectomy, 182, 271 I Id, 104, 122, 212, 217, 222, 224, 271 Idiopathic, 271, 303 Imaging procedures, 271, 312 Imidazole, 238, 269, 271 Immune function, 151, 271 Immune response, 15, 23, 44, 47, 54, 228, 233, 235, 249, 266, 267, 271, 272, 280, 308, 315, 316 Immune Sera, 271 Immune system, 24, 171, 235, 237, 271, 272, 277, 279, 284, 293, 314, 316 Immunity, 229, 271, 313 Immunization, 19, 23, 271, 272 Immunoassay, 62, 64, 65, 84, 90, 103, 108, 156, 168, 171, 175, 193, 194, 257, 271 Immunoblotting, 78, 271 Immunocompromised, 98, 271 Immunodeficiency, 65, 212, 271 Immunofluorescence, 7, 10, 12, 56, 65, 75, 271 Immunogenic, 146, 271, 300 Immunoglobulin, 19, 20, 65, 68, 116, 175, 193, 232, 261, 272, 283, 305 Immunohistochemistry, 5, 12, 18, 78, 98, 101, 272 Immunologic, 244, 271, 272, 300 Immunology, 15, 19, 58, 78, 90, 91, 96, 165, 228, 261, 269, 272 Immunophilins, 30, 272 Immunosuppressant, 261, 272 Immunosuppressive, 44, 264, 272, 310 Immunosuppressive therapy, 272 Immunotherapy, 15, 237, 272 Immunotoxins, 173, 272, 300 Impairment, 130, 182, 235, 244, 259, 272 Implant radiation, 272, 274, 275, 300, 316 Impotence, 166, 272 In situ, 5, 12, 18, 64, 69, 82, 87, 88, 134, 166, 180, 272 In Situ Hybridization, 5, 12, 18, 64, 69, 82, 87, 166, 272 In vivo, 6, 10, 15, 20, 23, 24, 26, 27, 29, 31, 32, 44, 54, 56, 57, 58, 59, 63, 68, 89, 96, 101, 114, 134, 154, 164, 176, 180, 190, 242, 268, 272, 310, 311 Incision, 272, 275 Incontinence, 3, 182, 272 Incubated, 12, 29, 190, 272 Incubation, 29, 272 Indicative, 166, 198, 272, 291, 315
328
Biotin
Infancy, 272, 273, 303 Infantile, 86, 117, 273 Infarction, 273, 301 Infection, 4, 7, 20, 29, 65, 103, 116, 123, 134, 141, 171, 230, 233, 234, 236, 237, 240, 241, 244, 256, 259, 263, 271, 273, 279, 291, 304, 308, 316, 317 Infectious Bursal Disease Virus, 88, 273 Infestation, 176, 273, 282 Infiltration, 5, 273, 317 Influenza, 273, 279 Infusion, 273, 313 Ingestion, 175, 265, 273 Inhalation, 175, 273 Initiation, 273, 312 Inlay, 273, 302 Inorganic, 14, 139, 270, 273, 287 Inositol, 182, 273 Inotropic, 254, 273 Insecticides, 273, 292 Insight, 7, 30, 273 Insomnia, 151, 274 Insulator, 274, 284 Insulin, 34, 37, 55, 57, 109, 124, 135, 157, 264, 274 Insulin-dependent diabetes mellitus, 274 Insulin-like, 34, 38, 274 Interferon, 79, 110, 274, 279 Interferon-alpha, 274 Interleukin-1, 79, 110, 274 Interleukin-2, 44, 58, 79, 89, 115, 274 Interleukin-4, 79, 110, 274 Interleukin-6, 34, 274 Intermittent, 274, 292 Internal Medicine, 143, 267, 274 Internal radiation, 274, 275, 300, 316 Interstitial, 28, 239, 274, 275, 281, 301, 316 Intestinal, 24, 35, 41, 57, 79, 119, 241, 264, 274, 280, 316 Intestine, 237, 239, 274, 277 Intracellular Membranes, 275, 281 Intraepithelial, 275 Intraperitoneal, 103, 275 Intrinsic, 25, 130, 152, 229, 236, 275 Inulin, 35, 275 Invasive, 28, 65, 72, 271, 275 Invertebrates, 264, 275 Involuntary, 3, 236, 258, 260, 275, 285 Iodine, 93, 149, 150, 159, 181, 200, 275 Ion Channels, 235, 275, 286 Ionization, 26, 42, 172, 275
Ions, 54, 155, 191, 192, 236, 240, 253, 255, 257, 270, 275, 276, 283, 298, 303, 306 Irradiation, 51, 275, 302, 316 Irritable Bowel Syndrome, 262, 275 Ischemia, 165, 235, 263, 275, 301 Isoelectric, 275, 308 Isoelectric Point, 275, 308 Isomerases, 272, 276 J Joint, 5, 104, 147, 234, 276, 289, 309, 310 Joint Capsule, 276, 310 Juniper, 150, 276 K Kb, 36, 132, 208, 276, 277 Keratin, 4, 276 Keratinocytes, 89, 98, 276 Keto, 60, 132, 146, 195, 276 Kidney Cortex, 276, 282 Kidney Disease, 208, 213, 276, 301 Kidney Failure, 200, 257, 264, 276 Kidney Failure, Acute, 276 Kidney Failure, Chronic, 276 Kilobase, 138, 277 Kinetic, 14, 52, 54, 95, 277 L Labile, 25, 247, 277 Laminin, 29, 236, 259, 277 Lanolin, 216, 277 Large Intestine, 274, 277, 301, 306 Lectin, 111, 142, 277, 281 Lens, 241, 277 Lesion, 277, 278 Leucine, 89, 277 Leukemia, 49, 69, 212, 245, 277 Leukocytes, 239, 244, 266, 274, 277, 292, 314 Leukotrienes, 234, 255, 277 Library Services, 222, 277 Life cycle, 7, 9, 238, 262, 277 Ligament, 277, 298 Ligands, 12, 15, 36, 39, 43, 46, 51, 52, 54, 62, 81, 134, 138, 145, 153, 161, 173, 184, 277, 309 Ligase, 61, 67, 71, 101, 138, 164, 172, 180, 277, 299 Ligation, 138, 277 Limb Bud, 10, 277 Linkage, 6, 25, 243, 262, 278, 293 Lipase, 163, 278, 290 Lipid Bilayers, 54, 278 Lipid Peroxidation, 20, 278, 290 Lipophilic, 153, 278
Index 329
Lipopolysaccharide, 35, 146, 266, 278, 307 Lipoprotein, 121, 133, 166, 254, 266, 278, 315 Liposomes, 173, 278 Litter, 115, 278 Liver Extracts, 150, 278 Lobe, 269, 278 Localization, 10, 73, 88, 90, 102, 116, 186, 272, 278 Localized, 136, 255, 256, 260, 273, 277, 278, 283, 294 Locomotion, 278, 294 Locoregional, 94, 278 Loop, 44, 51, 133, 158, 278 Low-density lipoprotein, 166, 254, 278 Lucida, 277, 278 Luciferase, 101, 279 Lycopene, 137, 149, 279 Lymph, 243, 249, 257, 269, 279, 303, 308 Lymph node, 243, 279, 303 Lymphatic, 257, 273, 279, 281, 306, 307, 311 Lymphatic system, 279, 306, 307, 311 Lymphoblastic, 279 Lymphoblasts, 227, 279 Lymphocyte, 10, 56, 109, 111, 233, 279, 280 Lymphocytic, 7, 279 Lymphocytic Choriomeningitis Virus, 7, 279 Lymphoid, 26, 232, 279 Lymphoma, 46, 212, 279 Lysine, 103, 152, 171, 179, 180, 268, 270, 279 Lysosomal Storage Diseases, 42, 279 Lytic, 279, 305 M Macronutrients, 149, 279 Macrophage, 26, 34, 274, 279 Macrophage Colony-Stimulating Factor, 34, 279 Major Histocompatibility Complex, 274, 280 Malabsorption, 212, 280 Malaise, 190, 280 Malformation, 10, 280 Malignancy, 280, 290 Malignant, 31, 93, 118, 212, 233, 280, 286, 300 Malnutrition, 168, 229, 235, 280, 284 Mammary, 12, 280 Mandible, 230, 280, 302 Manifest, 235, 280
Mannans, 262, 280 Mastitis, 280, 305 Matrix metalloproteinase, 84, 280 Meat, 146, 252, 280, 303 Mediate, 7, 13, 56, 136, 254, 280 Mediator, 274, 280, 305 Medicament, 280, 309 MEDLINE, 209, 211, 213, 280 Medullary, 29, 280 Megakaryocytes, 49, 239, 280 Megaloblastic, 252, 261, 281 Meiosis, 238, 281, 284, 309, 310, 314 Melanin, 281, 293, 314 Melanocytes, 281 Melanoma, 28, 31, 212, 281 Membrane Fusion, 39, 281 Membrane Proteins, 8, 16, 82, 278, 281 Memory, 53, 135, 232, 251, 281 Meninges, 243, 249, 281 Meningitis, 279, 281 Menopause, 4, 182, 281, 296 Menstrual Cycle, 281, 297 Menstruation, 281 Mental Health, iv, 5, 208, 210, 281, 299 Mental Processes, 253, 281, 299 Mercury, 261, 281 Mesenchymal, 157, 257, 279, 281 Metabolic disorder, 135, 265, 266, 281 Metabolite, 10, 143, 160, 238, 253, 281, 296 Metallothionein, 133, 155, 191, 282 Metaphase, 238, 282, 310, 314 Metastasis, 27, 28, 280, 282 Metastatic, 28, 31, 92, 282, 304 Methionine, 60, 73, 181, 253, 282, 309 MI, 103, 156, 166, 225, 282 Mice Minute Virus, 282, 291 Micelle, 147, 282 Microbe, 282, 312 Microbiology, 30, 58, 78, 91, 147, 228, 235, 282 Microgram, 261, 282 Micronutrients, 41, 149, 180, 282 Microorganism, 132, 139, 151, 152, 177, 187, 246, 282, 291, 316 Micro-organism, 139, 282, 304 Microscopy, 7, 10, 12, 18, 39, 50, 51, 54, 69, 73, 111, 138, 140, 236, 261, 269, 282, 288 Microspheres, 77, 138, 282 Migrans, 190, 282 Migration, 28, 282 Mitochondria, 12, 60, 181, 282, 289 Mitochondrial Swelling, 282, 285
330
Biotin
Mitosis, 233, 282, 283 Mitotic, 253, 283, 315 Mitotic inhibitors, 253, 283 Mobility, 54, 63, 283 Modeling, 254, 283 Modification, 22, 25, 48, 57, 134, 145, 147, 158, 162, 172, 173, 263, 283 Molecular mass, 42, 49, 283 Molecular Probes, 35, 283 Molecular Structure, 184, 283 Monitor, 283, 287 Monoamine, 33, 231, 283, 314 Monoamine Oxidase, 33, 231, 283, 314 Monoclonal, 13, 19, 46, 64, 65, 72, 75, 94, 144, 164, 269, 271, 272, 275, 283, 300, 316 Monoclonal antibodies, 19, 46, 65, 72, 75, 271, 272, 283 Monocyte, 34, 280, 283 Mononuclear, 9, 40, 53, 79, 80, 89, 91, 110, 114, 279, 283, 314 Monotherapy, 90, 284 Monounsaturated fat, 4, 284 Morphogenesis, 277, 284 Morphological, 18, 229, 255, 262, 281, 284 Morphology, 98, 267, 284 Motility, 262, 284, 305 Mucins, 284, 303 Mucosa, 273, 284, 308 Multiple Carboxylase Deficiency, 117, 127, 284 Multiple sclerosis, 56, 284 Multivalent, 102, 235, 284 Mung bean, 113, 284 Muscle Contraction, 255, 284, 303 Muscle Fibers, 284, 285, 313 Muscle Proteins, 51, 284 Muscular Atrophy, 212, 284 Muscular Dystrophies, 42, 255, 284 Mutagenesis, 12, 39, 55, 73, 284 Mutagenic, 50, 253, 284 Mutagens, 262, 284 Mutate, 27, 285 Mycobacterium, 69, 170, 285, 313 Myelin, 284, 285 Myelofibrosis, 49, 285 Myelogenous, 285 Myeloid Cells, 26, 285 Myocardial infarction, 166, 249, 282, 285 Myocardial Ischemia, 165, 285 Myocardium, 282, 285 Myofibrils, 255, 285 Myosin, 148, 284, 285, 313
Myotonic Dystrophy, 212, 285 N Nail Diseases, 140, 285 Nasopharynx, 285 Nausea, 263, 285, 314 NCI, 1, 8, 207, 245, 285 Necrosis, 86, 233, 273, 282, 285, 301, 302, 303 Neisseria, 77, 266, 285, 286 Neisseria gonorrhoeae, 77, 266, 286 Neonatal, 54, 107, 286 Neoplasia, 212, 286 Neoplasm, 286, 290 Neoplastic, 157, 167, 269, 279, 286, 310 Nephropathy, 65, 276, 286 Nephrosis, 286 Nephrotic, 199, 286 Nerve, 39, 228, 235, 249, 251, 262, 280, 283, 284, 286, 291, 296, 302, 304, 307, 313, 317 Nervous System, 26, 39, 56, 150, 151, 212, 227, 229, 231, 240, 243, 246, 262, 265, 277, 280, 284, 286, 292, 305, 309, 314, 315 Networks, 7, 26, 286 Neural, 231, 269, 283, 286, 306 Neuroblastoma, 15, 286 Neurodegenerative Diseases, 10, 30, 39, 236, 286 Neuroendocrine, 286, 310 Neurofilaments, 10, 286 Neurologic, 83, 286 Neurologic Manifestations, 83, 286 Neuronal, 34, 39, 165, 286, 304 Neurons, 10, 18, 34, 39, 48, 72, 103, 114, 246, 251, 262, 286, 309 Neuropeptide, 15, 286 Neurotransmitters, 286 Neutralization, 20, 286 Neutrons, 230, 275, 287, 299, 300 Niacin, 4, 150, 159, 167, 197, 198, 199, 200, 287, 313 Niacinamide, 4, 149, 180, 287 Nickel, 179, 287 Nitric Oxide, 114, 287 Nitrogen, 11, 14, 22, 40, 139, 140, 229, 230, 250, 259, 260, 276, 283, 287, 313 Nitrogen Oxides, 140, 287 Nitrogenase, 14, 287 Nonmetastatic, 28, 287 Norepinephrine, 33, 228, 254, 287 Nuclear Localization Signal, 52, 287 Nuclear Pore, 52, 287 Nuclear Proteins, 287
Index 331
Nuclei, 52, 92, 230, 248, 255, 263, 282, 287, 288, 298 Nucleic Acid Hybridization, 73, 154, 269, 288 Nucleic Acid Probes, 188, 288 Nucleolus, 288, 303 Nutritional Status, 109, 199, 288 Nutritive Value, 261, 288 O Odour, 234, 288 Ointments, 288, 291 Olfaction, 17, 288 Oligo, 153, 185, 288 Oligodeoxyribonucleotides, 62, 63, 288 Oligonucleotide Probes, 77, 288 Oligoribonucleotides, 63, 74, 288 Oligosaccharides, 25, 62, 104, 189, 289 Oliguria, 276, 289 Oncogene, 167, 212, 289 Oncogenic, 37, 289 Oocytes, 18, 289 Opacity, 251, 289 Operon, 63, 64, 68, 151, 289, 302 Ophthalmology, 260, 289 Opsin, 289, 302 Organ Culture, 289, 312 Organelles, 243, 245, 250, 281, 289 Oropharynx, 285, 289 Osmolarity, 6, 289 Osmoles, 289 Osmosis, 289 Osmotic, 141, 229, 282, 289, 305 Ossification, 289, 303 Osteoarthritis, 5, 168, 289 Osteoporosis, 182, 239, 289 Ovalbumin, 15, 289 Ovaries, 259, 290, 302 Overexpress, 54, 290 Ovum, 249, 264, 277, 290, 297, 316, 317 Oxidation, 10, 17, 20, 33, 41, 135, 227, 233, 236, 238, 250, 265, 278, 290 Oxidation-Reduction, 238, 290 Oxidative Stress, 168, 290 Oxides, 33, 287, 290 Oxygenation, 181, 290 Oxytetracycline, 159, 290 P Palate, 9, 285, 290, 308 Palliative, 290, 310 Pancreas, 227, 238, 274, 278, 290 Pancreatic, 212, 241, 290 Pancreatic cancer, 212, 290
Pancreatin, 150, 290 Papain, 150, 290 Papilloma, 37, 290 Papillomavirus, 132, 290 Paraffin, 18, 290 Parasite, 76, 291 Parasitic, 254, 267, 273, 291 Parasitism, 141, 291 Parathyroid, 291, 303 Parathyroid Glands, 291, 303 Parity, 121, 291 Parotid, 291, 303 Paroxysmal, 212, 267, 291 Particle, 31, 134, 168, 169, 172, 174, 175, 177, 178, 179, 191, 282, 291, 312 Parvovirus, 98, 282, 291 Patch, 50, 291 Pathogen, 37, 141, 272, 291 Pathogenesis, 9, 33, 55, 56, 291 Pathologic, 227, 233, 240, 249, 271, 291, 299, 302 Pathologic Processes, 233, 291 Pathologies, 170, 291 Pathophysiology, 32, 291 Patient Compliance, 57, 291 Patient Education, 216, 220, 222, 225, 291 Pelvic, 256, 291, 298 Penicillin, 75, 102, 124, 232, 291 Penis, 291, 293, 302 Pepsin, 150, 292 Peptide Mapping, 33, 292 Peripheral blood, 9, 46, 79, 80, 89, 91, 110, 114, 274, 292 Peripheral Nervous System, 286, 292, 308 Peripheral Vascular Disease, 166, 292 Peritoneal, 4, 200, 252, 275, 292 Peritoneal Cavity, 275, 292 Peritoneal Dialysis, 4, 200, 252, 292 Peritoneum, 292 Pernicious, 278, 281, 292 Pernicious anemia, 278, 292 Peroxidase, 107, 114, 144, 278, 292 Peroxide, 181, 292 Pesticides, 141, 268, 273, 292 Petrolatum, 256, 292 Petroleum, 290, 292 Phagocyte, 279, 293 Phallic, 260, 293 Pharmaceutic Aids, 261, 293 Pharmaceutical Preparations, 243, 258, 263, 293 Pharmacodynamic, 24, 293
332
Biotin
Pharmacokinetic, 20, 24, 293 Pharmacologic, 89, 114, 267, 293, 312 Phenolphthalein, 256, 293 Phenotype, 15, 28, 293 Phenyl, 158, 159, 293 Phenylalanine, 293, 314 Phlebotomy, 24, 293 Phosphatidic Acids, 293 Phosphatidylcholines, 54, 293 Phospholipases, 293, 305 Phospholipids, 54, 66, 148, 189, 259, 273, 278, 293 Phosphorous, 143, 293 Phosphorus, 4, 128, 143, 149, 150, 159, 181, 200, 240, 291, 293, 294 Phosphorylated, 41, 48, 55, 246, 294 Phosphorylation, 48, 55, 71, 137, 294 Physiologic, 229, 238, 267, 275, 281, 282, 294, 297, 300, 302 Pigment, 237, 244, 279, 281, 294, 302 Pilot study, 93, 118, 294 Placenta, 294, 297, 314 Plasma, 10, 13, 14, 16, 21, 24, 39, 45, 50, 55, 78, 93, 109, 115, 121, 146, 150, 229, 232, 242, 244, 255, 260, 263, 265, 267, 268, 270, 276, 294, 298, 301, 304, 305 Plasma cells, 232, 294 Plasma protein, 150, 229, 294, 298, 305 Plasmid, 59, 62, 73, 139, 194, 195, 294, 315 Plasticity, 268, 294 Platelet Activation, 294, 305 Platelet Aggregation, 231, 287, 294, 311 Platelet-Derived Growth Factor, 87, 294 Platelets, 49, 287, 294, 311 Platinum, 278, 295 Pleated, 276, 295 Point Mutation, 170, 295 Polycystic, 213, 295 Polyethylene, 173, 295 Polymerase, 7, 52, 65, 72, 164, 165, 186, 295, 302 Polymerase Chain Reaction, 65, 72, 186, 295 Polymers, 10, 51, 140, 152, 153, 179, 189, 191, 237, 295, 298 Polymorphism, 96, 295 Polypeptide, 39, 55, 132, 133, 179, 231, 247, 248, 257, 260, 269, 295, 297, 298, 317 Polyploid, 49, 295 Polyposis, 228, 295 Polysaccharide, 54, 73, 146, 191, 229, 233, 243, 295, 298
Polyunsaturated fat, 111, 112, 295, 311 Polyvalent, 32, 295 Porphyria, 293, 295, 296 Porphyria Cutanea Tarda, 293, 296 Posterior, 231, 235, 244, 254, 290, 296 Postmenopausal, 289, 296 Postnatal, 35, 296, 307 Postprandial, 135, 296 Postsynaptic, 296, 305, 309 Post-translational, 161, 296 Potassium, 4, 149, 150, 159, 160, 296 Potentiates, 274, 296 Potentiation, 296, 305 Practice Guidelines, 210, 296 Preclinical, 47, 296 Pregnancy Tests, 194, 296 Pregnenolone, 93, 296 Prenatal, 255, 296 Presynaptic, 296, 309, 310 Prickle, 276, 296 Probe, 11, 26, 37, 44, 50, 75, 87, 96, 97, 98, 138, 170, 177, 193, 288, 296 Prodrug, 13, 296 Proenzyme, 257, 296 Progeny, 26, 39, 248, 297 Progesterone, 108, 297, 307 Progression, 9, 25, 28, 33, 232, 297 Progressive, 49, 83, 242, 245, 251, 254, 266, 276, 284, 285, 286, 289, 294, 297, 301 Projection, 103, 251, 287, 297, 301 Proline, 39, 247, 270, 297 Promoter, 7, 194, 297, 300 Prone, 12, 297 Prophase, 238, 284, 289, 297, 309, 310, 314 Proportional, 257, 297, 309 Prostaglandin, 10, 108, 111, 250, 297, 311 Prostaglandin-Endoperoxide Synthase, 250, 297 Prostaglandins A, 297 Prostate, 81, 212, 297, 302 Protease, 30, 38, 47, 137, 290, 292, 298 Protease Inhibitors, 30, 298 Protein Conformation, 231, 276, 298 Protein Isoforms, 8, 230, 298 Protein S, 6, 29, 36, 37, 63, 113, 161, 170, 172, 187, 189, 213, 238, 263, 269, 298, 303 Protein-Energy Malnutrition, 109, 298 Proteinuria, 264, 298 Proteoglycan, 29, 298 Proteolytic, 230, 247, 260, 290, 298 Prothrombin, 78, 298, 311 Protocol, 78, 101, 159, 188, 298
Index 333
Protons, 230, 270, 298, 299 Protozoa, 248, 254, 282, 298 Proximal, 10, 253, 276, 296, 299 Pseudomonas, 62, 71, 139, 299 Psoralen, 71, 299 Psoriasis, 299 Psychiatry, 260, 299 Psychology, 253, 299 Psychomotor, 241, 299 Public Health, 20, 31, 166, 210, 299 Public Policy, 209, 299 Publishing, 59, 152, 198, 299 Pulmonary, 238, 244, 248, 276, 277, 299, 309, 315 Pulmonary Edema, 244, 276, 299 Pulse, 47, 283, 299 Purines, 236, 299, 305 Purulent, 286, 299, 315 Pyruvate Carboxylase, 71, 85, 113, 116, 127, 284, 299 R Race, 282, 299 Radiation, 31, 47, 94, 102, 103, 186, 235, 239, 255, 257, 259, 261, 262, 274, 275, 299, 300, 316 Radiation therapy, 31, 259, 262, 274, 275, 300, 316 Radioactive, 46, 58, 70, 73, 143, 162, 235, 267, 270, 272, 274, 275, 283, 287, 289, 300, 314, 316 Radioimmunoassay, 93, 261, 300 Radioimmunotherapy, 46, 83, 93, 94, 118, 300 Radioisotope, 43, 288, 300, 312 Radiolabeled, 31, 46, 98, 121, 239, 275, 300, 316 Radiopharmaceuticals, 77, 94, 300 Radiotherapy, 239, 275, 300, 316 Randomized, 22, 255, 300 Reagent, 19, 70, 71, 89, 92, 102, 137, 146, 162, 168, 194, 244, 270, 279, 300, 306 Receptors, Serotonin, 300, 305 Recombinant Fusion Proteins, 21, 300 Recombinant Proteins, 23, 90, 161, 301 Recombination, 248, 301 Reconstitution, 38, 301 Rectal, 132, 301 Rectum, 233, 239, 261, 263, 272, 277, 298, 301, 309 Red blood cells, 20, 21, 23, 258, 268, 296, 301, 303 Red Nucleus, 235, 301
Reductase, 11, 14, 22, 38, 41, 52, 53, 187, 301, 311 Refer, 1, 171, 240, 247, 260, 262, 268, 278, 287, 300, 301 Reference Values, 197, 301 Refraction, 301, 307 Regeneration, 154, 301 Regimen, 21, 135, 255, 291, 301 Rehydration, 32, 51, 301 Relapse, 46, 301 Reliability, 25, 301 Renal Artery, 166, 301 Renal failure, 28, 199, 301 Renal Osteodystrophy, 143, 301 Reperfusion, 165, 301, 302 Reperfusion Injury, 301, 302 Repopulation, 26, 302 Repressor, 63, 64, 67, 101, 195, 289, 302 Reproductive system, 12, 302 Resorption, 130, 239, 302 Respiration, 241, 244, 283, 302 Respiratory syncytial virus, 64, 75, 302 Response rate, 47, 302 Restoration, 112, 301, 302, 316 Retina, 245, 248, 277, 302, 303 Retinal, 50, 302 Retinal pigment epithelium, 50, 302 Retinoblastoma, 212, 302 Retinoid, 12, 302 Retinol, 50, 200, 302 Retrovirus, 134, 302 Reversion, 303, 314 Rhinitis, 303, 305 Riboflavin, 105, 150, 151, 159, 167, 180, 181, 182, 197, 198, 200, 303 Ribose, 164, 165, 228, 288, 303 Ribosome, 164, 303, 313 Rickets, 143, 303, 316 Rigidity, 294, 303 Risk factor, 166, 303 Rod, 6, 235, 236, 245, 299, 303, 307 Rodenticides, 292, 303 Ryanodine, 50, 303 S Saliva, 146, 303 Salivary, 88, 290, 303, 308 Salivary glands, 303 Saponins, 303, 307 Sarcoidosis, 143, 303 Sarcoplasmic Reticulum, 50, 303 Saturate, 172, 303 Saturated fat, 111, 303
334
Biotin
Scleroproteins, 276, 304 Sclerosis, 10, 27, 39, 212, 234, 284, 304 Screening, 7, 19, 42, 81, 83, 91, 94, 130, 160, 162, 184, 246, 304 Secondary tumor, 282, 304 Secretion, 101, 150, 188, 257, 269, 274, 284, 304 Secretory, 29, 66, 304, 309 Segmental, 264, 304 Seizures, 241, 291, 304 Selenium, 137, 149, 151, 157, 159, 167, 181, 200, 304 Semen, 298, 304 Semisynthetic, 240, 272, 304 Senile, 33, 123, 289, 304 Senile Plaques, 33, 304 Senility, 166, 304 Sensor, 7, 48, 131, 142, 304 Septicaemia, 304, 305 Sequence Analysis, 189, 304 Sequencing, 27, 29, 38, 42, 64, 66, 70, 73, 130, 162, 189, 295, 304 Serial Passage, 8, 304 Serine, 39, 159, 256, 305 Serologic, 60, 68, 73, 271, 305 Serologic Tests, 60, 305 Serotonin, 33, 237, 283, 300, 305, 313 Serotypes, 147, 251, 305 Serum Albumin, 300, 305 Sex Determination, 213, 305 Sharpness, 182, 305 Shock, 30, 165, 232, 305, 313 Side effect, 39, 136, 140, 151, 173, 182, 228, 237, 305, 312 Signal Transduction, 14, 97, 273, 305 Signs and Symptoms, 286, 301, 305 Silicon, 12, 153, 179, 183, 305, 306 Silicon Dioxide, 183, 305, 306 Silver Staining, 8, 111, 120, 306 Sindbis Virus, 230, 306 Skeletal, 18, 50, 143, 157, 245, 266, 284, 285, 303, 306, 313 Skeleton, 227, 239, 276, 297, 306 Skull, 249, 306, 310 Small intestine, 245, 254, 269, 274, 306 Smooth muscle, 45, 230, 231, 240, 248, 269, 306, 308 Social Problems, 171, 306 Sodium, 4, 32, 35, 149, 150, 159, 160, 266, 306, 315 Sodium Channels, 306, 315 Soft tissue, 239, 306
Solid tumor, 31, 232, 306 Solvent, 169, 258, 265, 289, 306 Somatic, 242, 256, 269, 281, 283, 292, 306 Somatic cells, 242, 281, 283, 306 Soybean Oil, 295, 306 Specialist, 217, 306 Specificity, 18, 29, 31, 44, 57, 63, 75, 101, 145, 147, 155, 163, 170, 173, 191, 229, 256, 307 Spectrin, 255, 307 Spectrometer, 22, 307 Spectrum, 14, 120, 174, 193, 199, 307 Sperm, 45, 245, 307, 313 Sphincters, 260, 307 Sphingomonas, 139, 307 Spike, 39, 307 Spinal cord, 234, 243, 244, 256, 262, 281, 286, 292, 307 Spinous, 258, 276, 307 Spirochete, 190, 307 Spleen, 279, 303, 307 Sporadic, 286, 296, 302, 307 Steel, 245, 307, 314 Stem Cells, 157, 258, 266, 307 Steroid, 93, 143, 237, 249, 296, 303, 307 Stimulant, 151, 231, 240, 269, 307 Stimulus, 16, 49, 255, 259, 275, 307, 311 Stomach, 227, 263, 265, 269, 285, 292, 306, 307, 308 Stomatitis, 168, 308 Stool, 3, 272, 275, 277, 308 Strand, 22, 108, 138, 165, 186, 295, 308 Streptomyces, 139, 158, 251, 290, 308, 310 Stress, 48, 135, 141, 168, 199, 242, 249, 262, 263, 275, 285, 290, 308 Stroke, 43, 165, 208, 241, 308 Stromal, 239, 256, 308 Stromal Cells, 239, 308 Structure-Activity Relationship, 300, 308 Subacute, 273, 308 Subarachnoid, 267, 308 Subclinical, 273, 304, 308 Subiculum, 268, 308 Submaxillary, 257, 308 Subspecies, 306, 308 Substance P, 281, 301, 304, 308 Substrate Specificity, 41, 172, 308 Suction, 260, 309 Sulfur, 11, 14, 22, 38, 40, 106, 159, 160, 259, 282, 309 Suppositories, 263, 309 Suppression, 186, 193, 252, 263, 309
Index 335
Surface Plasmon Resonance, 7, 88, 131, 309 Surfactant, 131, 309 Survival Rate, 47, 309 Sympathomimetic, 231, 254, 258, 287, 309, 314 Symphysis, 298, 309 Synapses, 34, 286, 307, 309, 310 Synapsis, 309 Synaptic, 34, 114, 305, 309 Synaptic Vesicles, 309 Synaptophysin, 34, 310 Synergistic, 22, 310 Synovial, 5, 276, 310 Synovial Fluid, 310 Synovial Membrane, 5, 276, 310 Systemic, 41, 232, 233, 238, 240, 258, 273, 275, 300, 303, 308, 310, 313, 316 Systolic, 271, 310 T Tacrolimus, 272, 310 Telangiectasia, 213, 310 Temporal, 13, 267, 268, 310 Teratogen, 186, 310 Teratogenesis, 25, 310 Teratogenic, 9, 90, 116, 253, 310 Testosterone, 301, 310 Tetravalent, 46, 310 Thalamic, 235, 310 Thalamic Diseases, 235, 310 Therapeutics, 44, 55, 153, 283, 310 Thermal, 153, 253, 287, 295, 310 Thiamine, 41, 69, 150, 159, 167, 180, 182, 200, 311 Thioredoxin, 11, 14, 22, 59, 311 Threonine, 305, 311 Threshold, 271, 311 Thrombin, 185, 260, 294, 298, 311 Thrombocytes, 294, 311 Thrombocytopenia, 49, 311 Thrombomodulin, 298, 311 Thrombosis, 78, 298, 308, 311 Thromboxanes, 234, 250, 255, 311 Thrombus, 249, 273, 285, 294, 311 Thylakoids, 244, 311 Thymidine, 29, 239, 311 Thymus, 271, 279, 311 Thyroid, 4, 271, 275, 291, 311, 312, 314 Thyroid Gland, 271, 291, 311, 312 Thyroid Hormones, 311, 314 Thyrotropin, 88, 311 Thyroxine, 229, 293, 311, 312
Ticks, 190, 273, 312 Tin, 156, 295, 312 Tissue, 5, 8, 18, 42, 43, 54, 63, 65, 102, 107, 111, 113, 115, 157, 161, 164, 173, 181, 182, 191, 228, 229, 232, 233, 235, 236, 238, 239, 240, 244, 246, 248, 254, 255, 256, 259, 260, 261, 262, 263, 265, 266, 269, 271, 273, 274, 277, 278, 279, 280, 281, 284, 285, 286, 288, 289, 291, 292, 294, 295, 301, 302, 304, 305, 306, 307, 308, 309, 312, 313, 316 Tissue Culture, 65, 312 Tissue Transplantation, 157, 312 Tolerance, 141, 227, 264, 312 Tomography, 191, 312 Tooth Preparation, 228, 312 Topical, 5, 125, 258, 270, 290, 291, 292, 312 Toxic, iv, 130, 162, 171, 181, 248, 251, 256, 257, 259, 266, 271, 272, 304, 312 Toxicity, 6, 46, 147, 153, 155, 171, 181, 254, 256, 281, 312 Toxicology, 48, 86, 210, 312 Toxins, 15, 18, 145, 150, 162, 176, 193, 233, 238, 256, 265, 272, 273, 283, 300, 312 Trace element, 199, 200, 245, 246, 287, 305, 312 Tracer, 24, 93, 103, 108, 156, 269, 312 Trachea, 311, 312 Traction, 245, 312 Transcriptase, 178, 186, 302, 312 Transcription Factors, 26, 66, 165, 312 Transduction, 16, 305, 312 Transfection, 54, 238, 312 Transfer Factor, 271, 313 Transferases, 265, 313 Transfusion, 23, 83, 313 Translation, 29, 47, 61, 300, 313 Translational, 161, 263, 313 Translocating, 184, 313 Translocation, 39, 69, 167, 184, 313 Transmitter, 227, 235, 254, 275, 280, 287, 309, 313, 314 Transplantation, 157, 245, 271, 276, 280, 313 Trauma, 285, 313 Triglyceride, 166, 271, 313 Trisomy, 167, 313 Trophic, 39, 313 Tropomyosin, 284, 313 Troponin, 284, 313 Tryptophan, 68, 73, 247, 305, 313 Tuberculosis, 69, 170, 171, 248, 313
336
Biotin
Tuberous Sclerosis, 213, 313 Tubulin, 118, 313 Tumor Necrosis Factor, 5, 82, 84, 314 Tumor suppressor gene, 167, 314 Tumorigenic, 34, 314 Tungsten, 53, 242, 314 Typhimurium, 132, 314 Tyramine, 78, 95, 97, 101, 144, 237, 283, 314 Tyrosine, 55, 254, 314 U Ubiquitin, 81, 314 Umbilical Arteries, 314 Umbilical Cord, 83, 314 Unconscious, 251, 271, 314 Univalent, 270, 290, 314 Urea, 55, 140, 182, 276, 314 Uremia, 4, 276, 301, 314 Ureters, 301, 314 Urethra, 292, 297, 314 Urinary, 121, 182, 264, 272, 289, 314 Urine, 76, 193, 194, 233, 238, 253, 257, 268, 272, 276, 289, 298, 303, 314 Uterus, 243, 249, 256, 259, 271, 281, 290, 297, 302, 314, 315 V Vaccine, 7, 15, 23, 132, 228, 298, 314 Vacuole, 77, 315 Vagina, 240, 243, 252, 281, 302, 315 Vaginitis, 240, 315 Valproic Acid, 90, 125, 315 Varicella, 64, 315 Vascular, 45, 56, 135, 158, 230, 232, 244, 257, 267, 273, 287, 294, 311, 315 Vasodilator, 239, 254, 269, 315 Vector, 31, 56, 58, 72, 134, 312, 315 Vegetative, 295, 315 Vein, 287, 291, 293, 314, 315 Venereal, 286, 315 Venous, 298, 315 Ventricle, 268, 299, 310, 315
Venules, 238, 240, 315 Vertebral, 104, 315 Veterinary Medicine, 209, 260, 315 Vinblastine, 313, 315 Vincristine, 313, 315 Viral, 7, 9, 39, 60, 132, 134, 162, 240, 256, 264, 273, 289, 302, 312, 314, 315, 316 Viral vector, 134, 315 Virion, 133, 236, 315 Virulence, 235, 305, 312, 315 Vital Statistics, 166, 316 Vitamin A, 149, 159, 181, 273, 302, 316 Vitamin D, 143, 159, 181, 199, 303, 316 Vitiligo, 299, 316 Vitro, 9, 11, 13, 15, 16, 20, 21, 23, 29, 32, 39, 44, 45, 48, 52, 54, 57, 58, 68, 128, 134, 157, 175, 180, 190, 242, 268, 272, 295, 304, 310, 312, 316 Volition, 275, 316 Voltage-gated, 50, 316 W Warts, 269, 316 Weight Gain, 182, 316 White blood cell, 227, 232, 245, 272, 277, 279, 283, 294, 316 Windpipe, 311, 316 Womb, 302, 314, 316 Wound Healing, 123, 280, 316 X Xenograft, 46, 47, 232, 316 X-ray, 22, 54, 55, 118, 158, 191, 242, 261, 262, 275, 287, 300, 316 X-ray therapy, 275, 316 Y Yeasts, 148, 240, 262, 293, 316 Yttrium, 92, 93, 118, 316 Z Zoster, 64, 317 Zygote, 248, 317 Zymogen, 257, 297, 298, 317
Index 337
338
Biotin
Index 339
340
Biotin
