ALBUMIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Albumin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00039-3 1. Albumin-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on albumin. 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 ALBUMIN .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Albumin ...................................................................................... 15 E-Journals: PubMed Central ....................................................................................................... 73 The National Library of Medicine: PubMed ................................................................................ 89 CHAPTER 2. NUTRITION AND ALBUMIN....................................................................................... 137 Overview.................................................................................................................................... 137 Finding Nutrition Studies on Albumin..................................................................................... 137 Federal Resources on Nutrition ................................................................................................. 143 Additional Web Resources ......................................................................................................... 144 CHAPTER 3. ALTERNATIVE MEDICINE AND ALBUMIN ................................................................ 145 Overview.................................................................................................................................... 145 National Center for Complementary and Alternative Medicine................................................ 145 Additional Web Resources ......................................................................................................... 153 General References ..................................................................................................................... 155 CHAPTER 4. DISSERTATIONS ON ALBUMIN .................................................................................. 157 Overview.................................................................................................................................... 157 Dissertations on Albumin.......................................................................................................... 157 Keeping Current ........................................................................................................................ 158 CHAPTER 5. PATENTS ON ALBUMIN ............................................................................................. 159 Overview.................................................................................................................................... 159 Patents on Albumin ................................................................................................................... 159 Patent Applications on Albumin ............................................................................................... 189 Keeping Current ........................................................................................................................ 222 CHAPTER 6. BOOKS ON ALBUMIN ................................................................................................. 223 Overview.................................................................................................................................... 223 Book Summaries: Federal Agencies............................................................................................ 223 Chapters on Albumin................................................................................................................. 224 CHAPTER 7. PERIODICALS AND NEWS ON ALBUMIN ................................................................... 227 Overview.................................................................................................................................... 227 News Services and Press Releases.............................................................................................. 227 Newsletter Articles .................................................................................................................... 231 Academic Periodicals covering Albumin ................................................................................... 232 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 235 Overview.................................................................................................................................... 235 U.S. Pharmacopeia..................................................................................................................... 235 Commercial Databases ............................................................................................................... 236 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 239 Overview.................................................................................................................................... 239 NIH Guidelines.......................................................................................................................... 239 NIH Databases........................................................................................................................... 241 Other Commercial Databases..................................................................................................... 243 The Genome Project and Albumin ............................................................................................. 243 APPENDIX B. PATIENT RESOURCES ............................................................................................... 247 Overview.................................................................................................................................... 247 Patient Guideline Sources.......................................................................................................... 247 Finding Associations.................................................................................................................. 249 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 251 Overview.................................................................................................................................... 251
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Preparation................................................................................................................................. 251 Finding a Local Medical Library................................................................................................ 251 Medical Libraries in the U.S. and Canada ................................................................................. 251 ONLINE GLOSSARIES................................................................................................................ 257 Online Dictionary Directories ................................................................................................... 258 ALBUMIN DICTIONARY ........................................................................................................... 261 INDEX .............................................................................................................................................. 373
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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 albumin is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about albumin, 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 albumin, 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 albumin. 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 albumin, 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 albumin. 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 ALBUMIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on albumin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and albumin, 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 “albumin” (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: •
Impact of Burn Size and Initial Serum Albumin Level on Acute Renal Failure Occurring in Major Burn Source: American Journal of Nephrology. 23: 55-60. January-February 2003. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479. Website: www.karger.com. Summary: Acute renal (kidney) failure (ARF) is not a rare occurrence in severe burns and is an important complication leading to an increase in mortality (death). The severity of the burn is largely determined by the burn size, and severe burns are likely to cause enough loss of extracellular fluid and albumin from plasma volume to produce shock and hypoalbuminemia (low levels of the protein albumin in the blood). This article reports on a study in which the authors hypothesized that initial serum albumin
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level may be useful as an indicator of prognosis and severity of injury in burned patients. The authors retrospectively analyzed the clinical characteristics of 147 adult patients with second-and third-degree burns covering 30 percent or more of their body surface area. Of the 147 patients, 27 (19 percent) experienced ARF, defined as a serum creatinine greater than 2 milligrams per deciliter, during the admission. The patients with ARF had larger burn size and lower serum albumin concentration at admission, compared with those without ARF. All patients with ARF expired, whereas 29.4 percent (35 of 119 patients) of the patients without ARF died. The burn size greater than 65 percent was associated with a risk of ARF that was 9.9 times and with a risk of death that was 14.2 times as high as that for burn size less than 65 percent. The authors conclude that when major burns are complicated by ARF, the mortality rate increases significantly. Burn size is an independent predictor of ARF occurring in major burns. Initially depressed serum albumin level is associated with an increase in mortality in the major burn patients. 3 figures. 4 tables. 21 references. •
Albumin in the Treatment of Liver Diseases: New Features of a Classical Treatment Source: Alimentary Pharmacology and Therapeutics. 16 (Suppl 5): 1-5. December 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email:
[email protected]. Website: www.blackwell-science.com. Summary: Albumin was introduced initially in the treatment of patients with cirrhosis (liver scarring) and ascites (fluid accumulation) to increase serum albumin concentration due to its oncotic (expansion) effect. Although its administration declined some years later, at present it constitutes an essential treatment in clinical hepatology (treatment of liver diseases). Several studies have clearly demonstrated its effectiveness in the prevention and treatment of circulatory dysfunction and hepatorenal (liver and kidney) syndrome in patients with cirrhosis. These effects can be due not only to its properties as a plasma expander but also to its capacity to bind numerous substances such as bile acids, nitric oxide, and cytokines. Based on this capacity, an albumin dialysis system (MARS, the Molecular Adsorbents Recirculating System) has recently been developed. This article considers the usefulness of this system in the management of patients with acute and chronic liver failure. 43 references.
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Albumin Testing Methods Differ: Implications for the Dialysis Patient Source: Dialysis and Transplantation. 23(6): 282-283, 286. June 1994. Summary: Albumin, which has long been used as an indicator of nutritional status in renal failure, is one portion of the criteria screens used by end-stage renal disease (ESRD) networks when performing medical case review in dialysis facilities. In this article, the authors discuss the implications for the dialysis patient of different albumin testing methods. The authors report on a study in which 216 serum albumin values from 72 randomly selected patients were analyzed. The two methods used for albumin analysis were bromcresol green (BCG) and bromcresol purple (BCP). In both methods, a dye chemically attaches to the albumin molecule, thereby changing the absorbance of the dye in proportion to the amount of albumin present. The authors conclude that knowing which test each laboratory uses can assist nephrology teams in accurately assessing patients' nutritional status and determining appropriate intervention. 3 tables. 11 references.
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Clinical Evaluation of a Test for Immediate and Quantitative Determination of Urinary Albumin-to-Creatinine Ratio: A Brief Report Source: Diabetes Care. 21(1): 97-98. January 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: Diabetic nephropathy (kidney disease related to diabetes mellitus) constitutes the most common single cause of end-stage renal failure in both the United States and Europe. Improved glycemic control and antihypertensive treatment (to keep blood pressure under control) can postpone and possibly prevent development of nephropathy in patients with diabetes who demonstrate microalbuminuria (microscopic protein in the urine). However, to have the maximum preventive effects, these interventions must be instituted very early in the development of diabetic nephropathy. This article offers a clinical evaluation of a new test for immediate and quantitative determination of the urinary albumin-to-creatinine ratio. Because screening needs to be a continuous process, development of methods that are both reliable and suitable for patients is important. Reagent strips (dip stick strips) have the advantage of providing an immediate result, but they provide only semiquantative results and are subject to possible errors from alterations in urine concentration. The spot urinary albumin to creatinine ratio performed using quantitative chemical methodology has been convenient for the patient and superior to reagent strips because the creatinine correction accounts for possible errors in urine concentration. The authors conclude that the DCA 2000 microalbumin to creatinine assay provides an immediate, quantitative, and accurate tool for the detection of microalbuminuria. It complements the DCA 2000 HbA1c (glycosylated hemoglobin) assay in the care of diabetes. 1 figure. 1 table. 5 references.
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High-Normal Blood Pressure and Microalbuminuria Source: American Journal of Kidney Diseases. 41(3): 588-595. March 2003. Summary: High-normal blood pressure (BP) is associated with increased cardiovascular risk compared with optimal BP, but no study has specifically examined the association between high-normal BP and microalbuminuria (microscopic protein in the urine), an established predictor of future cardiovascular events. This article reports on a crosssectional study of normotensive individuals without diabetes with no hypertension history enrolled in the Third National Health and Nutrition Examination Survey (NHANES). BP was categorized as high normal, normal, and optimal. Results showed that compared with optimal BP, high-normal BP was significantly associated with increased odds of microalbuminuria. 6 tables. 28 references.
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Microalbuminuria in Hypertensive Nonproteinuric Renal Transplant Recipients: Influence of Previous Acute Rejection Episodes and Sodium Intake Source: Transplantation Proceedings. 34(3): 801-802. May 2002. Contact: Available from Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010. (212) 633-3730. Website: www.elsevier.com. Summary: In recent years, microalbuminuria (microscopic protein in the urine) has been proposed as a marker of cardiovascular risk in the general population. Kidney (renal) transplant recipients constitute a population with a high risk of cardiovascular complications and deterioration of renal function. The use of an early marker of cardiovascular and renal risk would be extremely valuable in this population, because it
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would allow optimal protection with intensive therapeutic measures. Microalbuminuria could represent this marker. However, causes of abnormal urinary albumin excretion are numerous, including urinary tract infection, chronic rejection, cyclosporine nephrotoxicity (kidney damage), and recurrence of original renal disease. In this article, the authors report on a study that assessed the determinants of microalbuminuria in nonproteinuric renal transplant recipients. In the study, renal transplant recipients with microalbuminuria were younger, had higher arterial pressure and higher incidence of natriuresis (sodium in the urine), and a more frequent history of acute rejection episodes than those with normoalbuminuria. However, they had similar body weight, renal function, cyclosporine trough level, lipids, and fasting glucose. Many determinants of microalbuminuria in renal transplant patients are thus different from those in the general population. Therefore, microalbuminuria in the kidney transplant recipient is probably not a good marker of cardiovascular risk. 9 references. •
Blood Glucose Control and Albuminuria in Type 1 Diabetes Mellitus Source: Journal of Pediatrics. 119(2): 178-182. August 1991. Summary: In this article, the authors report on a study in which the relationship between long-term blood glucose control and albuminuria in insulin-dependent diabetes mellitus (IDDM) was investigated in 42 male and 58 female patients who had had diabetes for more than 7 years. For periods of observation ranging from 1 to 6 years, hemoglobin A1C was measured two to six times yearly. Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The results of this research support the contention that maintenance of hemoglobin A1C levels at no more than 9 percent (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop.
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Microalbuminuria in the U.S. Population: Third National Health and Nutrition Examination Survey Source: American Journal of Kidney Diseases. 39(3): 445-459. March 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Microalbuminuria (MA, microscopic protein in the urine) is associated with adverse health outcomes in adults with diabetes and hypertension (high blood pressure). The prevalence and clinical significance of MA in nondiabetic populations is less clear. This article reports on a study undertaken to generate national estimates of the prevalence of MA in the U.S. population. Untimed urinary albumin concentrations (UACs) and creatinine (a measure of kidney function) concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria was similar for males and females. However, the prevalence of MA was significantly lower in males compared with females. MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar aged non Hispanic whites. MA prevalence was 28.8 percent in persons with previously diagnosed diabetes, 16 percent in those with hypertension, and 5.1 percent in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40 years and older, after excluding persons with clinical proteinuria, albuminuria was
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independently associated with older age, non Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. The authors conclude that MA is common, even among persons without diabetes or hypertension. Age, sex, race or ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates. 5 figures. 3 tables. 68 references. •
Increase in Nocturnal Blood Pressure and Progression To Microalbuminuria in Type 1 Diabetes Source: New England Journal of Medicine. 347(11): 797-805. September 12, 2002. Contact: Available from New England Journal of Medicine. 860 Winter Street, Waltham, MA 02451-1413. (781) 893-3800. Website: www.nejm.org. Summary: Patients with type 1 diabetes mellitus and microalbuminuria (microscopic protein in the urine) often have elevated blood pressure while they are asleep, but it is not known whether the elevation develops concomitantly with microalbuminuria or precedes it. This article reports on a study of 75 adolescents and young adults with type 1 diabetes with normal urinary albumin excretion and blood pressure for more than five years. Ambulatory blood pressure monitoring was used to assess blood pressure at the initial evaluation and about two years later, at which time all subjects had normal urinary albumin excretion. Subsequently, subjects were monitored for the development of microalbuminuria. Microalbuminuria developed in 14 subjects, whereas the other 61 continued to have normal urinary albumin excretion. The mean systolic pressure during sleep increased significantly in the subjects who ultimately had microalbuminuria, but not in the subjects with normal albumin excretion. The authors conclude that in persons with type 1 diabetes, an increase in systolic blood pressure during sleep precedes the development of microalbuminuria. In those whose blood pressure during sleep decreases normally, the progression from normal albumin excretion to microalbuminuria appears to be less likely. 4 figures. 2 tables. 37 references.
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Association Between Serum Albumin and Root Caries in Community-Dwelling Older Adults Source: Journal of Dental Research. 82(3): 218-222. 2003. Summary: Recently, associations between dental diseases and general health have been reported. This article reports on a study undertaken to evaluate, by serum albumin (protein in the blood) concentrations, the relationship between the general health condition and root caries (cavities in the tooth root). The authors randomly selected 763 individuals (600 70-year-olds and 163 80-year-olds) living in Niigata City, Japan. The variables of body composition, blood measurements, daily nutrient intakes, and root caries were measured. The relationship between root caries and serum albumin concentration was evaluated. The findings indicate that a relationship between root caries and serum albumin concentration in these elderly subjects is highly possible. 1 figure. 3 tables. 23 references.
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Simplified Screening for Microalbuminuria Source: Annals of Internal Medicine. 127(9): 817-819. November 1, 1997. Summary: Screening for microalbuminuria is increasingly advocated as a way to diagnose early renal involvement in diabetes and other diseases. It usually entails the use of a radioimmunoassay that is expensive and not always readily available. This article reports on a study undertaken to assess the efficacy of three simple and
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inexpensive tests for ruling out microalbuminuria. The cross-sectional study consisted of 221 patients from primary care clinics and a diabetes clinic. Random urine specimens were tested for albumin using Micral-Test immunoassay strips and for protein by using sulfosalicylic acid testing and impregnated dipsticks. Radioimmunoassay for albumin was used for all specimens as a standard for comparison. When less than 20 mg per liter was considered the upper limit of normal for albumin concentration, Micral-Test, sulfosalicylic acid testing, and Chemstrips had negative predictive values of 99 percent, 95 percent, and 96 percent, respectively. Seventy-four specimens tested negative on both sulfosalicylic acid and Chemstrips; the negative predictive value of these two tests combined was 99 percent. The authors conclude that this combination was as good as and less expensive than Micral-Test in ruling out microalbuminuria. However, all three screening tests yielded high rates of false-positive results on a single testing. This indicates the need to repeatedly test specimens that have positive results and proceed to radioimmunoassay if necessary. 1 table. 19 references. (AA-M). •
Is Microalbuminuria a Predictor of Cardiovascular and Renal Disease in Patients with Essential Hypertension? (editorial) Source: Current Opinion in Nephrology and Hypertension. 9(2): 143-147. March 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: The term microalbuminuria refers to urinary albumin excretion (UAE, protein in the urine) that is below amounts detectable by semiquantitative methods (such as a urine dipstick). The use of microalbuminuria to predict the development of kidney failure in patients with diabetes has been well documented, and recently published research suggests that the predictive value of microalbuminuria may extend to patients with essential hypertension. The authors discuss the incidence of microalbuminuria in patients with essential hypertension, its relationship with blood pressure levels and other cardiovascular risk factors, and the evidence supporting its role in predicting cardiovascular as well as renal complications. The authors review related research in these areas, conducted over the past year. The authors conclude that there are no sufficient data to support the notion that microalbuminuria can predict the risk of progressive renal disease in patients with essential hypertension. Larger prospective studies are necessary to determine this role. 83 references.
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Prevalence of Microalbuminuria in Diabetic Children and Adolescents and Its Relation to Puberty: Summary and Comment Source: Diabetes Spectrum. 2(4): 254-255. July-August 1989. Summary: This article comments on a study conducted by Dahlquist and Rudberg [Acta Paediatric Scandinavica 76: 795-800, 1987] into microalbuminuria as an indicator for subsequent development of diabetic nephropathy. The study showed a 20 percent prevalence of microalbuminuria in children with insulin dependent diabetes mellitus and a strong correlation between microalbuminuria and age of the patient as well as between microalbuminuria and arterial blood pressure. It is recommended that microalbuminuria be screened and blood pressure be measured systematically in children over 12 years of age who have diabetes, but that no special therapeutic measures be instituted until two or three urine collections demonstrate the presence of microalbuminuria. Also recommended are two or three short daytime urine collections to determine the albumin/creatinine ratios. 4 references.
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Use of Enalapril to Attenuate Decline in Renal Function in Normotensive, Normoalbuminuric Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial Source: Annals of Internal Medicine. 128(12, Part 1): 982-988. June 15, 1998. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: This article describes a randomized, double-blind, placebo controlled trial of the effect of angiotensin-converting enzyme (ACE) inhibition on renal function and albuminuria in patients with type 2 diabetes. A total of 156 patients with type 2 diabetes from 8 outpatient clinics in the greater Tel Aviv area completed the study. These patients were diagnosed after age 40, and they had a baseline mean blood pressure of less than 107 mm Hg and albuminuria. After a 2-month observation period, patients were randomly assigned in a double-blind manner to receive enalapril or placebo. Results indicate that enalapril therapy decreased albumin excretion from a mean plus or minus SD of 11.6 plus or minus 7 mg/24 hours to 9.7 plus or minus 6 mg/24 hours at 2 years. This was followed by a gradual increase to 15.8 plus or minus 8 mg/24 hours at 6 years. In the placebo group, albumin excretion increased from 10.8 plus or minus 8 mg/24 hours to 26.5 plus or minus 10 mg/24 hours at 6 years. Transition to microalbuminuria occurred in 15 of 79 placebo recipients and 5 of 77 enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5 percent for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 plus or minus 0.13 mL/s to 1.63 plus or minus 0.12 mL/s in enalapril recipients and from 1.81 plus or minus 0.15 mL/s to 1.57 plus or minus 0.17 mL/s in placebo recipients. Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal in all patients. The article concludes that enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy. 2 figures. 2 tables. 33 references. (AA-M).
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Reduction of ACE Activity Is Insufficient to Decrease Microalbuminuria in Normotensive Patients with Type 1 Diabetes Source: Diabetes Care. 24(5): 919-924. May 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that determined whether the reduction of urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes is dependent on changes of blood pressure or if interference with the renin-angiotensin system is sufficient to explain the effects of angiotensin converting enzyme (ACE) inhibition on UAER. The study was conducted in six centers in Sweden. Ramipril was administered double blind at a dose of 1.25 mg to 19 patients and a dose of 5.0 mg to 18 patients and compared with placebo in 18 patients after a single blind placebo period of 1 to 4 weeks. The 55 patients were followed for 2 years. ACE activity and plasma renin activity (PRA) were measured to document an effect on the renin-angiotensin system. In addition, 24 hour ambulatory blood pressure was recorded at baseline and repeated after 1 and 2 years using an ambulatory blood pressure recording device. The study found that both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo. However, neither ambulatory nor clinic
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blood pressure was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 or year 2, after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. The article concludes that treatment with ramipril did not affect microalbuminuria or clinic or ambulatory blood pressure. On the basis of the present study, researchers question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in blood pressure is not demonstrated. 1 figure. 3 tables. 32 references. (AA-M). •
Screening and Management of Microalbuminuria in Patients With Diabetes Mellitus: Recommendations to the Scientific Advisory Board of the National Kidney Foundation from an Ad Hoc Committee of the Council Source: American Journal of Kidney Diseases. 25(1): 107-112. January 1995. Contact: Available from W.B. Saunders Company. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This article presents recommendations for the screening and management of microalbuminuria in patients with diabetes mellitus. The authors stress that all individuals with diabetes mellitus should be screened yearly with a spot urine albumin to creatinine ratio to identify those who are at increased risk for the development of complications of diabetes mellitus, including nephropathy, retinopathy, and cardiovascular disease. Once these high-risk individuals are appropriately identified, the authors recommend that therapy with an angiotensin-converting enzyme (ACE) inhibitor be initiated. In addition, cardiovascular risk factors should be investigated, and when, appropriate, therapeutic interventions should be initiated according to existing recommendations. The authors discuss the need for evaluation of the effects of the described microalbuminuria screening and intervention, as well as the health economic impact of such testing. 2 figures. 7 references. (AA-M).
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Risk Factors for Microalbuminuria in Black Americans with Newly Diagnosed Type 2 Diabetes Source: American Journal of Kidney Diseases. 36(5): 903-913. November 2000. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This article reports on a cross sectional analysis performed to describe the prevalence of and risk factors for microalbuminuria (microscopic protein in the urine) among blacks with newly diagnosed type 2 diabetes mellitus. Black adults with diagnosed type 2 diabetes mellitus of 2 years' duration or less, who presented for care to the Grady Diabetes Clinic (Atlanta, GA) between January 1994 and December 1996 were eligible (n = 1,167). Information obtained at the initial visit included age; sex; body mass index (BMI); serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, C peptide, serum creatinine, and hemoglobin A1c levels; and seated systolic and diastolic blood pressures. Of 1,044 patients studied, macroalbuminuria was present in 3.8 percent and microalbuminuria in 23.4 percent. The relationship between HbA1c level and microalbuminuria was stronger in patients with lower BMIs. The authors conclude that microalbuminuria prevalence was high in this population of urban blacks with newly diagnosed type 2 diabetes. Risk factors associated with increased albumin creatinine levels in the urine included male gender,
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poor glycemic control, endogenous hyperinsulinemia (high levels of insulin in the blood), high blood pressure (hypertension), elevated triglyceride levels, and obesity. The authors encourage physicians to screen patients with newly diagnosed diabetes with the albumin creatinine ratio from a random urine sample to identify those patients with the earliest signs of kidney damage; in this way, intervention can be initiated in this high risk group. 2 figures. 6 tables. 55 references. •
Microalbuminuria in Type I Diabetic Patients: Prevalence and Clinical Characteristics Source: Diabetes Care. 15(4): 495-501. April 1992. Summary: This article reports on a study designed to estimate the prevalence of microalbuminuria, overnight urinary albumin excretion rate (AER) in a large sequential sample of nonhypertensive patients with insulin-dependent diabetes (IDDM) attending hospital diabetes clinics. The authors also hoped to identify micro-and normoalbuminuric patients in this sample for subsequent intervention and natural history follow-up studies and to compare the clinical characteristics of the patients identified. A patient population of 1,888 was screened. Results showed that microalbuminuria in IDDM, which appears to represent an earlier phase in the development of clinical nephropathy, is associated with elevated blood pressure and a longer duration of diabetes. 1 figure. 2 tables. 32 references. (AA-M).
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Glycosylated Hemoglobin and the Risk of Microalbuminuria in Patients with Insulin-Dependent Diabetes Mellitus Source: New England Journal of Medicine. 332(19): 1251-1255. May 11, 1995. Summary: This article reports on a study in which researchers measured urinary albumin excretion in three random urine samples, obtained at least one month apart, from 1,613 patients with insulin-dependent diabetes mellitus (IDDM). The researchers wanted to determine the relation between the degree of hyperglycemia and urinary albumin excretion. Measurements of glycosylated hemoglobin obtained up to four years before the urine testing were used as an index of hyperglycemia. The prevalence of microalbuminuria was 18 percent in patients with IDDM. The risk of microalbuminuria in patients with IDDM increases abruptly above a hemoglobin A1 value of 10.1 percent (equivalent to a hemoglobin A1C value of 8.1 percent), suggesting that efforts to reduce the frequency of diabetic nephropathy should be focused on reducing hemoglobin A1 values that are above this threshold. 1 figure. 2 tables. 32 references.
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Association of Dietary Protein Intake and Microalbuminuria in Healthy Adults: Third National Health and Nutrition Examination Survey Source: American Journal of Kidney Diseases. 41(3): 580-587. March 2003. Summary: This article reports on a study that investigated whether dietary protein intake (DPI) was associated with urinary albumin (protein) level in a population sample of persons with normal kidney function. The authors used the population of adults aged 20 to 80 years from the Third National Health and Nutrition Examination Survey (NHANES, n = 12,422). In analyses adjusted for sociodemographic characteristics and coronary heart disease risk factors, DPI was not associated with microalbuminuria (MA, protein in the urine) in normotensive or nondiabetic persons. Persons in the highest quintile of DPI who had both hypertension and diabetes (n = 634) had a significantly elevated odds ratio for MA compared with those in the lowest quintile. The authors conclude that DPI is not associated with MA in healthy persons or those with isolated hypertension or diabetes. However, in persons with both conditions, high DPI is
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associated with increased prevalence of MA. These findings suggest the need for further research on weight-loss strategies for high-risk persons. 1 figure. 3 tables. 30 references. •
Diabetes in Urban African-Americans. II.: High Prevalence of Microalbuminuria and Nephropathy in African-Americans with Diabetes Source: Diabetes Care. 18(7): 955-961. July 1995. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study to evaluate the prevalence of and risk factors for renal disease in an African-American population with diabetes. The authors measured urine albumin excretion in 578 consecutive patients; subjects provided 24hour and/or about 3-hour urine collections for measurement of albumin and creatinine. Among African Americans with NIDDM (n=466), the estimated prevalence of microalbuminuria was 24 percent and that of nephropathy was 12 percent; prevalence remained high among 219 patients with less than 1-year known duration of diabetes. In this study, clinically significant albuminuria occurred in 36 percent of persons at first presentation. The authors conclude with a call for screening for albuminuria and aggressive treatment of hypertension in urban populations of African Americans with diabetes. 2 figures. 2 tables. 37 references. (AA-M).
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Animal Versus Plant Protein Meals in Individuals with Type 2 Diabetes and Microalbuminuria: Effects on Renal, Glycemic, and Lipid Parameters Source: Diabetes Care. 25(8): 1277-1282. August 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to determine, for individuals with type 2 diabetes and microalbuminuria (microscopic protein in the urine), the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP, 60 percent animal, 40 percent plant) on kidney (renal) function and secondarily on glycemia, lipid levels, and blood pressure. In the randomized crossover trial, the authors compared the 6 weeks of meals in 17 subjects with type 2 diabetes and microalbuminuria who were treated with diet and or oral antidiabetes agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6 week period, subjects were studied for 36 hours on a metabolic unit. There were no significant differences between diets for glomerular filtration rate (GFR, a measure of kidney function), renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA1c (glycosylated hemoglobin, a measure of blood glucose over time), blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower, HbA1c had significantly improved, and diastolic blood pressure was significantly lower. The authors conclude that there is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, health diet, regardless of protein source. 3 tables. 36 references.
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On the Trail of a Diabetes Cure: Research on IDDM Leads from Bovine Milk Albumin to Bioengineered Islet Cells Source: Medical World News. 33(8): 16-17. September 1992. Summary: This article reviews recent research advances in the search for a cure for diabetes mellitus. The author notes that dozens of different approaches to primary, secondary, and tertiary prevention of insulin-dependent diabetes mellitus (IDDM) are now being pursued around the world. Topics include genetics and genetically susceptible persons; the use of insulin prophylactically; the role of nicotinamide, a B vitamin, in the immune system's attack against beta cells in humans; immune system suppressors, including the use of azathioprine; islet-cell transplants and various adaptations therein; and the introduction of a gene that permits glucose-mediated insulin secretion in a clonal cell line. 1 figure. 1 table.
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Predictors of Renal and Cardiovascular Mortality in Patients with Non-InsulinDependent Diabetes: A Brief Overview of Microalbuminuria and Insulin Resistance Source: Journal of Diabetes and Its Complications. 11(6): 352-357. November-December 1997. Contact: Available from Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010. Summary: This article reviews the incidence of microalbuminuria (protein in the urine) and insulin resistance and their role as predictors of renal and cardiovascular mortality in patients with type 2 diabetes. Both microalbuminuria and insulin resistance are present at some stage in the natural history of type 2 diabetes. Microalbuminuria predicts both progression to end-stage renal disease (ESRD) and an increase in cardiovascular mortality compared to diabetic patients without microalbuminuria. Conversely, microalbuminuria is not a strong predictor of either renal or cardiovascular mortality in hypertensive nondiabetic subjects. The difference in risk may relate to the presence of glycated albumin in patients with diabetes. Glycation of albumin occurs because of persistent hyperglycemia. Glycated albumin is directly toxic to both renal and vascular tissue through stimulation of reactive oxygen species by both renal and immune protective cells. Blunting the rise in microalbuminuria with either aggressive blood glucose control or ACE inhibition, early in the course of the disease, markedly reduces renal mortality. In contrast to microalbuminuria, which is a reflection of renal injury, insulin resistance is a genetically determined problem that directly relates to peripheral glucose utilization. In most cases, insulin resistance is phenotypically expressed as diabetes as a result of environmental factors such as obesity. Insulin resistance is associated with an increased risk for development of both hypertension and type 2 diabetes as well as atherosclerosis. Diabetic or hypertensive subjects with insulin resistance have an increased risk of cardiovascular but not renal mortality. Sustained weight loss is the best way to reduce insulin resistance and arterial pressure. Additionally, alpha blockers, more than other antihypertensive agents, reduce insulin resistance. This class of drugs, however, has not been shown to reduce either microalbuminuria or overall cardiorenal mortality. 2 figures. 1 table. 42 references. (AAM).
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Nature of Microalbuminuria, Proteinuria, and Progressive Renal Disease (Introduction to Symposium on Protein-Urea and Progressive Renal Disease) Source: Journal of Diabetes and Its Complications. 9(1): 2-6. January-March 1995.
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Contact: Available from Elsevier Science, Inc. 655 Avenue of the Americas, New York, NY 10010. Summary: This article serves as a brief summary of the second symposium on proteinuria and progressive renal disease, a symposium convened to consider general strategies for the prevention of end-stage renal disease (ESRD). In this article, the author focuses on the nature of microalbuminura, proteinuria, and progressive renal disease. Topics covered include the prevalence of ESRD worldwide; the focus on single nephron hyperfiltration as a means of identifying early pathogenesis; albumin excretion rates; the natural history of hypertension as related to microalbuminuria; microalbuminuria in diabetes mellitus; the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in the patient with microalbuminuria; the prevention of progression in diabetic renal disease with antihypertensive treatment and ACE inhibitors; and the role of strict blood pressure control in nondiabetic renal disease. The author concludes that screening and effective early antihypertensive treatment are the fundamentals in the prevention of progression of renal disease. 90 references. •
Prevention of Diabetic Renal Disease with Special Reference to Microalbuminuria Source: Lancet. 346(8982): 1080-1084. October 21, 1995. Summary: This review article considers the prevention of diabetic renal disease. The authors focus on microalbuminuria because this is the first clinically identifiable sign of risk of diabetic nephropathy and other vascular complications; in addition, the authors feel that prevention is best achieved at this early stage. The authors describe the recommended screening and confirmatory procedures. All recommendations propose careful blood pressure (BP) screening because BP is often raised in patients with microalbuminuria; minimum levels for intervention are 140 over 90 mm Hg (for patients younger than age 60), and 160 over 90 mm Hg (patients aged 60 years and older). The authors propose that treatment aimed at renal disease should begin when microalbuminuria is detected, irrespective of BP, especially in young individuals with diabetes. Early antihypertensive treatment, especially with angiotensin-converting enzyme (ACE) inhibitors will reduce or stabilize microalbuminuria and preserve glomerular filtration rate (GFR, a measure of kidney function). The authors recommend starting an ACE inhibitor at a low dose, gradually titrating the dose to achieve the desired reduction in BP and urine albumin excretion without adversely affecting serum potassium or creatinine. During treatment, BP and microalbuminuria must be monitored, every 1 to 3 months at first. The authors stress that this program is very cost effective, mainly because treatment for end-stage renal disease (ESRD) is so expensive. 1 figure. 3 tables. 49 references. (AA-M).
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Determinants of Progression of Microalbuminuria in Patients With NIDDM: A Prospective Study Source: Diabetes Care. 20(6): 999-1005. June 1997. Summary: This study identifies the determinants of progression of microalbuminuria (MA) in noninsulin-dependent diabetes (NIDDM, or Type II) patients. It is generally acknowledged that MA is not a static condition. It develops in patients who at one time must have had normal albumin excretion rates, and it progresses further to macroalbuminuria in a number of patients. The researchers attempt to provide insight into the characteristics and the degree of variability of MA's progression. In addition, they examine the factors that are related to the rate of progression of MA. They determine that dyslipidemia and the use of ACE inhibitors are two such factors. Other
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factors, such as smoking, glycemic control, serum creatinine, and cholesterol levels, do not predict its progression. The researchers conclude that NIDDM patients with MA and controlled blood pressure are not a uniform group. While some patients have relatively stable MA, others show rapid progression towards overt proteinuria. 4 figures. 3 tables. 36 references. (AA-M). •
Association of the Insulin Resistance Syndrome and Microalbuminuria Among Nondiabetic Native Americans. The Inter-Tribal Heart Project Source: JASN. Journal of the American Society of Nephrology. 13(6): 1626-1634. June 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: This study investigated the association between microalbuminuria (the presence of microscopic protein in the urine) and the insulin resistance syndrome (IRS) among nondiabetic Native Americans. In a cross-sectional survey, age-stratified random samples were drawn from the Indian Health Service clinic lists for one Menominee and two Chippewa reservations. Information was collected from physical examinations, personal interviews, and blood and urine samples. the urinary albumin to creatinine ratio (ACR) was measured using a random spot urine sample. The IRS was defined by the number of composite traits: hypertension (high blood pressure), impaired fasting glucose (IFG), high fasting insulin, low HDL cholesterol, and hypertriglyceridemia (high levels of blood fats). Among the 934 eligible non-diabetic participants, 15.2 percent exhibited microalbuminuria. The prevalence of one, two, and three or more traits was 17.0 percent, 16.6 percent and 7.4 percent, respectively. Of the individual IRS traits, only hypertension and IFG were associated with microalbuminuria. Among these nondiabetic Native Americans, the IRS was associated with a twofold increased prevalence of microalbuminuria. The authors conclude that health promotion efforts should focus on lowering the prevalence of hypertension, as well as glucose intolerance and obesity, in this population at high risk for renal and cardiovascular disease. 1 figure. 4 tables. 47 references.
Federally Funded Research on Albumin The U.S. Government supports a variety of research studies relating to albumin. 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 albumin. 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 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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animals or simulated models to explore albumin. The following is typical of the type of information found when searching the CRISP database for albumin: •
Project Title: A MOUSE MODEL OF GAUCHER DISEASE Principal Investigator & Institution: Beutler, Ernest N.; Chairman; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-JAN-2006 Summary: (provided by applicant): An animal model of Gaucher disease could be of great value in studying treatment strategies and some features of the pathogenesis of the disease. However, attempts to create such a model have been unsuccessful. The knockout mouse proved to be lethal at about the time of birth. We have now created a murine model of Gaucher disease by creating a chimeric mouse, transplanting wildtype mice with liver-derived hematopoietic stem cells from knockout fetuses. The peripheral blood and spleen from these animals is deficient in glucocerebrosidase activity and the amount of glucocerebroside in the liver and spleen is increased. Moreover, intravenous loading of the animals with glucocerebroside/albumin given intravenously increases the glucocerebroside levels further. We propose to further exploit this model by studying the natural history of glucocerebroside accumulation and by attempting to load these animals in a more convenient and possibly more physiologic manner. Such loading techniques might consist of intraperitoneal injection of glucocerebroside or the increase of blood cell turnover by the administration of G-CSF or phenylhydrazine. A "readout" that is more facile than chemical determination of glucocerebroside by HPLC will also be explored. In particular, electron microscopy and light microscopy will be used to attempt to demonstrate the development of Gaucher cells in the chimeric mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A NOVEL REGULATOR OF PI-3-KINASE IN HUMAN LIVER CANCER Principal Investigator & Institution: Defrances, Marie C.; Assistant Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 05-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The phosphatidylinositol-3-kinase (PI3K) pathway is upregulated in a variety of human cancers, such as hepatocellular carcinoma (HCC), and is thought to promote proliferation, motility and survival of tumor cells. Class la PI3Ks are lipid kinases consisting of two subunits: a p85 regulatory subunit and a p110 catalytic subunit. The molecular mechanisms responsible for down regulation of active p110 are not known. Recently, we discovered a novel kringle containing transmembrane protein we call zPA that harbors a p85-1ike domain in its C-terminal, intracellular portion. Our preliminary experiments show that zPA associates with the p110 subunit of PI3K possibly through its p85-1ike domain and that it inhibits the enzymatic activity of p110. We demonstrate that induced zPA overexpression downregulates cell growth and cell survival in liver and other tumor cells in vitro and in vivo. In human liver tumor tissues (i.e. hepatocellular carcinoma [HCC] and hepatoblastoma [HB]), zPA protein levels are altered as compared to adjacent or non-malignant liver in western blot analysis. The molecular mechanisms underlying primary human liver cancer, such as HCC and HB, are ill-defined, but aberrant tyrosine kinase and PI3K signaling may be involved. Based on these and other preliminary data, we hypothesize that zPA binds to the p110 subunit of PI3K to downregulate its enzymatic activity, and accordingly, functions as a negative growth regulator. To test this hypothesis in liver growth and
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neoplasia, we propose three specific aims: Aim 1--to determine the molecular mechanism(s) through which zPA exerts its effect on liver cell growth regulation. We will characterize the molecular interaction of zPA with the pl 10 subunit of PI3K in liver cells, analyze the proteolytic processing of zPA protein, and identify proteins other than p110 that interact with zPA. Aim 2--to determine the expression and association patterns of zPA and p110 as well as the mutational profiles of the zPA gene in normal, diseased and malignant human liver tissues. Aim 3--to examine the in vivo function of zPA in liver growth, regeneration and tumorigenesis through gain-of-function and loss-offunction animal models. We have generated transgenic mice to overexpress zPA in the liver under the transcriptional regulation of the albumin promoter/enhancer. We propose to produce a liver specific knock out mouse model of zPA. Together, these studies should provide clues about the role of zPA and the PI3K pathway in normal and aberrant liver growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A RODENT MODEL TO STUDY TOXICOLOGY AND HUMAN VIRUSES Principal Investigator & Institution: Hall, Cornell-Bell; Hepaticus, Inc. 5 Science Park, Ste 7 New Haven, Ct 06511 Timing: Fiscal Year 2003; Project Start 16-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): A study of human hepatocytes is hindered by hepatocyte loss of liver-specific functions as de-differentiation occurs during cell culture. Hepaticus Inc has liscenced the technology to fill this need from Drs. George and Catherine Wu of University of CT Health Center. Injection of human hepatocytes into the peritoneum of embryonic rats results in a new born "tolerized" rat that does not mount an immune reaction to later transplantion with human hepatocytes. This unique system provides an inexpensive environment to study pathogenesis, immunology, natural history, and viral replication of Hepatitis B and C and other human liver diseases with immunologic component(s) including other forms of hepatitis, and autoimmune diseases. The Hepaticus system augments rodent cell studies with data from human cells that maintain human-specific functions. This is one step closer to testing a drug candidate in human patients without the risk. Multiple compounds can be studied at one time, helping to identify potential metabolic interactions. We will use several methods to show that human hepatocytes transplanted into the rat maintain human specific functions over time. We will show that Cytochrome P450 levels are preserved in the human hepatocytes using a Vivid Cytochrome P450 kit with specific substrates for human enzymes. The majority of drug-drug interactions are metabolismbased where two or more drugs compete for the same enzymes, usually members of the Cytochrome P450 family. We will also show that normal human hepatocytes continue to produce human albumin protein. The purpose of this proposal is to confirm that human hepatocytes harvested from a single transplant donor will propagate and maintain human-specific liver enzyme functions when transplanted into a tolerized rat. We will pre-label normal human hepatocytes prior to transplantation with a fluorescent dye, CFSE. Using enzymes the tissue will be dissocated and the isolated cells will be FACS sorted using flow cytometry methods to separate the human hepatocytes from rat cells. Molecular biological methods will be used to show human hepatocytes produce message for human albumin as well as humain albumin protein, thus further corroborating that hepatocytes maintain human-specific characteristics when grown in a liver from a tolerized rat. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIRWAY PERFUSION ASSISTED LIQUID VENTILATOR Principal Investigator & Institution: Parker, James C.; Professor; Mallard Medical Co., Inc. 20268 Skypark Dr Redding, Ca 96002 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-JUL-2004 Summary: (provided by applicant): We have developed and patented (U.S. Pat No. 5,706,830) a new type of closed circuit perfluorocarbon (PFC) liquid ventilator with enhanced capabilities for gas exchange and exudates clearance from the lungs. This system has potential application to rescue of patients in acute respiratory failure and treatment of cystic fibrosis. The system employs a continuous isovolumetric perfusion (bias flow) of oxygenated PFC through one lumen of a double lumen endotracheal catheter that is superimposed on tidal liquid ventilation (liv). Phase I studies in newborn piglets indicate that bias flow significantly improved blood gases and increased the clearance of a five percent albumin solution from the lung by over 3-fold. During Phase II we propose to finalize the prototype design and control system software for ventilatory parameters and a feedback control of lung liquid volume based on measurements of end-expiratory stop-flow pressures. High performance pulseless pumps, an oxygenator and vapor recovery system will be included as well as protective algorithms and relief valves to limit airway pressure excursions. Phase II experimental studies in piglets and rabbits will examine novel applications of TLV with bias flow for sustaining arterial blood gases during oleic acid lung injury, increasing the clearance rate of five percent albumin solution and mucus-like gels from the lung, and enhancing the homogeneity of gene expression for a reporter gene introduced during TLV. We will also apply for an Investigational Device Exemption (IDE) from the Food and Drug Administration during Phase II to distribute ventilator prototypes to research institutions. PROPOSED COMMERCIAL APPLICATION: This liquid ventilator will be used in infant and adult intensive care units to treat end-stage respiratory failure as a lower cost alternative to extracorporeal oxygenation. Other applications include continuous intrapulmonary administration of drugs and anesthetics and clearance of material from the lungs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALBUMINURIA GENES IN MEXICAN AMERICANS WITH DIABETES Principal Investigator & Institution: Abboud, Hanna E.; Professor & Director; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The pathogenesis of diabetic nephropathy (DN) is not well understood but circumstantial evidence indicates a genetic basis. Microalbuminuria and macroalbuminuria/proteinuria are important markers of DN and predict renal progression and risk of cardiovascular morbidity and mortality. Urinary albumin excretion, measured as albumin to creatinine ratio (ACR), has been shown to be heritable in our preliminary analysis of urine data on 405 participants of San Antonio Family Diabetes Study (SAFADS), initially recruited on the basis of type 2 diabetic proband. Preliminary multipoint linkage analysis for albuminuria involving 335 genotyped individuals using urine albumin to urine creatinine ratio equal to or >.03 as a discrete trait showed strong evidence of linkage to a genetic location near marker GABRB3 on chromosome 15 (LOD = 3.3). The gene for tight junction protein-1 (TJP-1) has been mapped to a chromosomal region very close to the linkage signal identified. TJP-1 is a peripheral membrane-associated protein that is believed to play a central role
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in organizing the highly modified tight junction known as slit diaphragm of the glomerular epithelial cells. We have phenotyped approximately a total of 700 individuals from the 39 families enrolled in SAFADS. We will extend genotyping and analysis to all participants whose phenotypic data for DN are now available but who have not yet been genotyped (300 individuals), in order to confirm susceptibility loci for albuminuria by increasing the power of the linkage analysis. We will investigate positional candidate genes(s) influencing susceptibility to albuminuria, by identifying DNA sequence variants that are responsible for the linkage signal. We will focus on our selected candidate gene, TJP-1, by first identifying variants (single nucleotide polymorphisms - SNPs) within the upstream promoter region, 5' and 3' untranslated regions (UTR), exons, and splice sites of the TJP-1 gene that are present in our MexicanAmerican SAFADS population by direct sequencing. For each variant identified, we will genotype all 700 individuals. We will conduct a conditional linkage/linkage disequilibrium analysis to determine whether one or more SNPs are responsible for the linkage signal. Variants of this gene that impair its proper function could, hence, lead to increased glomerular capillary permeability and albuminuria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMADORI-MODIFIED ALBUMIN IN DIABETIC NEPHROPATHY Principal Investigator & Institution: Ziyadeh, Fuad N.; Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2004 Summary: The mechanisms mediating kidney damage in diabetes mellitus undoubtedly stem from chronic hyperglycemia, but the intermediary steps are not completely understood. Evidence is accumulating that increased nonenzymatic glycation of proteins represents a mechanistic link between hyperglycemia and renal pathobiology. Glucose-derived modifications of proteins alter their functional and structural properties. In vivo, circulating glycated proteins principally exist as Amadori products (as opposed to advanced glycation products), and their concentration is significantly increased in diabetes with exposure to a hyperglycemic milieu. Recent focus on pathophysiologic events induced by advanced glycation has shifted attention from the possible role of Amadori- modified proteins in the development of diabetic complications. However, our published data with mesangial cells in culture and in the db/db diabetic mice have show that: Amadori-modified glucose adducts in albumin (GA) induce significant alterations in glomerular cell biology that resemble those of transforming growth factor-beta (TGF-b), a multi- functional cytokine with potent antiproliferative and pro-fibrogenic activity; increased GA in diabetes is linked to increased bioactivity of the TGF-b/TGF-b receptor system; and neutralization of biologically active epitopes in GA ameliorates the structural and functional abnormalities characteristic of diabetic renal disease in db/db mice. The general plan of this project is to further investigate the role of GA and its molecular mediators in the increased accumulation of extracellular matrix (ECM) and the decrement in renal function characteristic of diabetic nephropathy. The Specific Aims are 1) to establish that increased expression of TGF-b1 is required for GA- stimulated ECM production; 2) to investigate that mechanism(s) underlying the increased expression of the TGF-b signaling receptors in mesangial cells grown with GA; 3) to examine the nature of the intracellular signal that mediates the stimulatory effect of GA on the production of TGFb1; and 4) to establish that GA mediates up-regulation of the TGF-b1/TGF-b receptor system in the kidney and promotes long-term renal pathobiology in diabetic mice. A major component of these studies will be interventional arms in which we will
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administer neutralizing anti-GA and anti-TGF-b murine monoclonal antibodies to diabetic mice to prove that mesangial ECM expansion is caused by up-regulation of the renal TGF-b system. Understanding the mechanisms underlying up- regulation of the renal TGF-b system resulting from increased concentrations of GA may lead to the conceptual design of novel therapeutic interventions that could prevent the deleterious effects of diabetes on the kidney. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMYLOID BETA PEPTIDE AND THEIR BINDING PROTEINS Principal Investigator & Institution: Wisniewski, Thomas M.; Associate Professor; Neurology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract): The defining neuropathological lesions of AD are the deposition of amyloid beta (Abeta) in the form of amyloid fibrils in congophilic angiopathy and senile plaques, as well as the presence of neurofibrillary tangles. The Abeta in neuritic plaques is predominantly 1-42, while in vessels it is mainly Abeta1-40. Preamyloid lesions, the earliest types of Abeta deposits, are mainly Abeta17-42. Abeta peptides are also found in all biological fluids, with a main sequence of Abeta1-40. The latter is called soluble Abeta (sAbeta). Since Abeta peptides are produced throughout the body and can cross the blood brain barrier (BBB) in both directions, it remains unknown why amyloid deposition in AD occurs only in the brain. In this grant we will test the hypothesis that the clearance of brain sAbeta and its deposition is significantly affected by its binding proteins, such as apolipoprotein (apo)E. In the plasma sabeta is thought to be bound to apoJ, albumin or transthyretin. On the other hand, we have preliminary evidence that brain sAbeta in AD patients is partially bound to apoE, a protein that does not cross the BBB. Previously we have reported that in neuritic plaques amyoid Abeta is partially complexed to a carboxyl fragment of presenilin-1, a protein which is linked to the majority of early onset familial AD. In this grant we will determine how apoE and other Abeta peptide binding proteins interact with Abeta1-42, 1-40 and 17-42, to influence their passage across the BBB from the brain, as well as their conformation, aggregation state, toxicity in tissue culture and their ability to bind to senile plaques in vivo. We plan to: 1) Determine how much sAbeta from brain tissue is complexed to apoE and other proteins in normal controls versus AD and DS patients of differing ages and apoE isotopes. This will ascertain the importance of brain sAbeta-apoE complexes in AD pathogenesis. 2) Determine the influence of apoE and other sAbeta binding proteins on the conformation of Abeta1-42, 1-40 and 17-42 using FT-IR, circular dichromism and other methods. The influence of these binding proteins in tissue culture will be determined. 3) Determine if labeled Abeta1-40, 1-42 and 17-42 alone and with different binding proteins can cross the BBB either from ventricular or systemic injections in a transgenic model of AD, as well as in aged monkeys, with vessel amyloid and parenchymal Abeta deposits. We will also identify if any of these labeled peptides are deposited on the Abeta lesions, in vivo. The latter could be used to develop a diagnostic test for AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASSESSING FUNCTIONAL OUTCOMES IN ADOLESCENT WITH ESRD Principal Investigator & Institution: Furth, Susan L.; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218
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Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAR-2004 Summary: provided by applicant): Dr. Furth is seeking the Small Grant Award to expand the study of clinical outcomes for children with end stage renal disease (ESRD) initiated under her KO8 Award DK 02586-01A1. With the support of the KO8 funding, Dr. Furth has completed her PhD in Clinical Investigation and has begun the transition to an independent research career. She has published a number of manuscripts using her training in epidemiology and clinical investigation: examining how clinical and socio-economic factors affect access to different treatment regimens for children with kidney failure, and how clinical experience with ESRD care for children affects treatment decisions. She has examined how poor growth, a crucial pediatric issue, affects mortality, hospitalization rates and educational achievement. She has also initiated a multi-center, cross-sectional study comparing functional outcomes/ health related quality of life (HRQL) for pediatric patients with chronic renal failure or ESRD treated with hemodialysis, peritoneal dialysis or transplant. Resources provided by the RO3 award will allow Dr. Furth to expand the multi-center study of health related quality of life in adolescents with ESRD to a prospective study. A prospective study will allow Dr. Furth to determine whether specific measures of health related quality of life are sensitive to clinical changes, as patients proceed from dialysis to transplantation. The supplementary funding of the R03, additionally will allow Dr. Furth to examine the link between clinical measures such as hematocrit, serum albumin, and dialysis adequacy (Kt/V) and functional outcome/HRQL. Furthermore, the prospective study will assess whether high risk behavior characterized by patterns of response on an adolescent health status questionnaire can predict non-compliance with therapy, increased hospitalization rates, acute rejection or transplant failure. The measures of functional outcome studied will include the Child Health and Illness Profile-Adolescent Edition, and the Child Health Questionnaire (Parent report). This research will provide an indepth analysis of a measure of functional outcome in children with ESRD, and will provide valuable information regarding optimal treatment choices for children with kidney disease. If assessments of high risk behavior predict increased rates of hospitalization, rejection or transplant failure, results of this study will allow identification of a high risk population of adolescents with ESRD, who can be targeted for early intervention and close follow-up to improve long term outcomes of care. The proposal addresses several priority areas for Clinical Research highlighted in the NIH Task Force publication, Research Needs in Pediatric Kidney Disease: 2000 and beyond. During this project, Dr. Furth will gain new skills in organizing and coordinating a prospective multi-center clinical research study. This experience will give Dr. Furth the tools she needs to develop into an independent clinical investigator in a nurturing academic environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: B CELL REPERTOIRE AND B CELL NEOPLASMS IN OLD MICE Principal Investigator & Institution: Weksler, Marc E.; Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The long-term goal of this project is to explore the mechanisms underlying the progression of transient to persistent B Lineage Clonal Expansions (BLCE) in middle-aged mice and the progression of persistent BLCE to latelife B cell neoplasms. We hypothesize that an ordered progression of genetic alterations underlies this age-associated progression. Our first aim is to isolate antigen-specific BLCE prior to the appearance of antigen-specific serum monoclonal immunoglobulin
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(mlg) and antigen-specific clonal BM plasma cells after the appearance of antigenspecific mlg or diffuse large cell lymphoma (DLCL) from DNP-human serum albumin (DNP-HSA)- or hen egg lysozyme (HEL)-immunized C57/BL/6 mice. The transient or stable antigen-specific BLCE will be isolated from cryopreserved, spleen cells obtained by partial splenectomy of 4-6- and 14-18-month-old mice. BM plasma cells secreting antigen-specific mIg will be isolated from bone marrow obtained from mice sacrificed at 19-months of age with antigen-specific mIg. The antigen-specific cells will be stained with fluorescent-labeled antigen. Results obtained in immunized mice will be confirmed by isolating spontaneous, stable BLCE, bone marrow plasma cell-secreting mIg, or DLCL. Spontaneous BLCE will be isolated from cryopreserved spleen cells obtained prior to the development of mIg or DLCL by their surface or intracellular binding of fluorescent-labeled anti-clonotypic antibody. The link between antigen-induced or spontaneous BLCE and neoplastic B cells will be established by identifying signature IgH/IgL CDR3 sequences of the neoplastic cells and their stable BLCE precursors by single-cell RT-PCR. Our second aim is to develop a genetic roadmap defining the progression of BLCE into late-life B-cell neoplasms. We shall define the genetic abnormalities that accumulate during the transformation of transient to stable BLCE and stable BLCE to mIg-secreting bone marrow plasma cells and/or to DLCL. BLCE isolated from mice prior to the development of B cell neoplasms will be analyzed for the presence somatic hypermutation of proto-oncogenes by single cell RT-PCR, for chromosomal translocations and aneuploidy by FISH and for proto-oncogene expression by quantitative RT-PCR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BENZO[I]PHENANTHRIDINES: TOP1-TARGETING ANTITUMOR AGENTS Principal Investigator & Institution: Lavoie, Edmond J.; Professor/Chair; Pharmaceutical Chemistry; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): Topoisomerase I (TOP1) is an enzyme that alters the topology of DNA by transiently breaking one DNA strand. TOP1-targeting anticancer agents exert their cytotoxic activity by trapping an abortive enzyme-DNA cleavable complex, converting TOP1 into a cellular poison. Camptothecin (CPT) was the first TOP1 poison identified. The poor solubility of this alkaloid, the metabolic instability of its lactone moiety and the high binding affinity to human serum albumin of its hydrolysis product are among the obstacles that hampered clinical development of this first generation of TOP1-targeting anticancer agents. Despite these shortcomings, there are two derivatives of CPT (Irinotecan, and Topotecan) in clinical use. The focus of this proposal is to advance the development of benzo[i]phenanthridines and related compounds as a novel class TOP1-targeting anticancer agents. It is our hypothesis that within this class of noncamptothecin TOP1-targeting agents, there are compounds that 1) have enhanced chemical and metabolic stability and 2) are able to overcome known mechanisms of resistance that do affect the cytotoxic activity of CPT analogues. Such attributes within a second generation of TOP1-targeting anticancer agents may provide the basis for broader clinical utility as well as improved efficacy. The specific aims of this proposal are 1) Evaluate select benzo[i]phenanthridines, azabenzo[i]phenanthridines, and azadibenzo[c,h]cinnolines as novel TOP1-targeting agents capable of overcoming multidrug resistance associated with efflux transporters such as BCRP, as well as MDR1 (P-glycoprotein), MRP1, and LRP; 2) to assess in vivo
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efficacy using various human tumor cell lines, including those that express MDR1 and BCRP and 3) characterize the metabolism and bioavailability of ARC-111 (azabenzo[i]phenanthridine analogue) and ARC-31 (an azadibenzo[c,h]cinnoline). While ARC-111 and ARC-31 possess potent TOP1-targeting activity and cytotoxicity, these compounds differ in regard to their relative efficacy in vivo. Our laboratory has identified several compounds structurally-related to benzo[i]phenanthridines with similar potency to CPT in TOP1-targeting activity and cytotoxicity. The exceptional in vitro and in vivo biological activities of benzo[i]phenanthridines, azabenzo[i]phenanthridines and azadibenzo[c,h]cinnolines observed in our laboratory form the basis for the studies proposed to advance our understanding of these potentially clinically-useful agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXCRETION
BILIRUBIN
AND
PHOTOBILIRUBIN/METABOLISM
AND
Principal Investigator & Institution: Mcdonagh, Antony F.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-1980; Project End 31-MAR-2003 Summary: Long-term objectives of this proposal are to elucidate the molecular mechanisms responsible for the therapeutic effects of phototherapy of neonatal jaundice; to improve the effectiveness and safety of phototherapy; and to define, at the molecular level, structural features that control the transport, metabolism and excretion of bilirubin and related compounds by the liver. Specific aims are: To determine by 13Cnuclear magnetic resonance, circular dichroism and other spectroscopic methods, dissociation constants and three- dimensional structures of bilirubin, its glucuronides and its photoisomers in biologically relevant environments. To clarify the interdependent roles of vinyl substitution, intramolecular hydrogen bonding, acidity, and lipophilicity on the photobiology and biochemistry of bilirubin. To elucidate the mechanisms involved in photoisomerization reactions of bilirubin-albumin complexes and define factors that influence their stereoselectivities and quantum yields. To investigate the importance in phototherapy of a newly discovered photoisomer of bilirubin. To evaluate the contribution of the canalicular anion transporter c- MOAT to the biliary excretion of bilirubin photoisomers and other tetrapyrrolic carboxylate anions and glucuronides. To define the topography and substrate requirements of the active site of bilirubin glucuronyl transferase by studying the glucuronidation of chemically engineered bilirubins of defined three dimensional structure. To synthesize bilirubin glucuronides and novel bilirubins with potential research and clinical applications and test new chemotherapeutic strategies for inhibiting bilirubin production. These aims will be achieved by measuring the chemical and biological properties of bilirubin and related compounds in vitro and by studying the transport and metabolism of phototherapy intermediates and bilirubin model compounds in normal rats and in mutant rats with congenital defects in bilirubin metabolism. The project is directly related to the prevention of bilirubin-induced brain damage in babies and in patients with the CriglerNajjar syndrome, to the diagnosis and understanding the hepatobiliary disease and jaundice, and to the therapeutic and biological effects of light on humans. The work will lead to safer and more effective methods for the treatment of familial hyperbilirubinemia and jaundice in the newborn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOCOMPATIBLE PEG-FUNCTIONALIZED METHACRYLATES Principal Investigator & Institution: Collins, William E.; Associate Professor; Chemical Engineering; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Applicant's Abstract) This project investigates the potential of functionalizing poly methyl methcrylate (PMMA) with poly (ethylene glycol) (PEG) to inhibit epithelial cell in growth and inflammatory reactions to the prospective intraocular lens. PMMA displays strong posterior attachment, but some in-growth. Trace functionalization with PEG will further inhibit undesired biological responses without disturbing the strong posterior attachment of PMMA. A suitable in vitro experimental model will measure these responses at low cost to determine if in vivo pursuit is worthwhile. This model uses the human corneal epithelial cell line HCE- I as an epithelial cell model. HCE-1 cells will be cultured, passaged and placed onto the different biomaterials. Adherent cells will be visualized and counted using inverted microscopy and computerized image analysis. Adhesion will be based on the spread area/cell and fraction of biomaterial surface occupied by adherent cells. HCE-1 cells will be incubated on bare and protein-preadsorbed PEG-functionalized PMMA to reveal the role of proteins in promoting cell adhesion. The proteins selected are human fibronectin, an adhesive RGD protein, and serum albumin, a nonadhesive protein. Human fibronectin will be isolated from citrated whole human blood and characterized, including its biological activity. Protein adsorption will be quantified radiolabelling proteins with 125, using the chloramine-T method. This project will synthesize and characterize PMMA pendantly functionalized with poly(ethylene glycol), including ESCA and contact angle goniometry. Goniometry of protein-preadsorbed polymers will be endeavored. Macrophage adhesion will be quantified to appraise possible inflammatory reactions that these biomaterials can elicit. Macrophages will isolated from whole human blood by centrifugation on a Ficoll-Hypaque gradient. Macrophage chemotaxis and phagocytosis will be assessed. The morphology of adherent macrophages and HCE- I cells will also be examined with scanning electron microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOTHREAT DETECTION WITH IMPROVED BACKGROUND REJECTION Principal Investigator & Institution: Kebabian, Paul L.; Aerodyne Research, Inc. Billerica, Ma 01821 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The Quartz Crystal Microbalance (QCM) is a wellestablished technology for quantifying small changes in mass. The long-term objective of this program is to improve the QCM so that it is suitable for use as a field test for the common, foodborne bacteria. To do this, we will modify the standard quartz crystal (QC) used in the QCM so as to increase its background rejection capabilities. This will involve innovations to the design of the QC used as the detector to the electronics. We will utilize standard technology to deposit a uniform coating of antibody directed against E. coli onto the surface of the QC. We will use utilize commercially available preparations of E. coli and Pseudomonas to demonstrate that the innovations introduced to the QC design and the electronics of the QCM allow a single QC to serve as both the experimental and the reference detectors. Thus, the modified QCM can discriminate between specific and non-specific binding of mass to the QC. We will use a second antibody, labeled with horseradish peroxidase to generate an insoluble reaction
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product to further amplify the mass of bacteria attached to the QC. Furthermore, we will utilize glutaraldehyde to non-selectively bind bovine serum albumin to antibody on the surface of both the conventional and modified QCs. Only the modified QC will be able to discriminate between specific binding of E. coli to the antibody and the non-specific cross-linking of BSA to antibody. We believe that our innovations will be of particular value in field tests in which there will be relatively small amounts of pathogenic agent and relatively large amounts of nonhazardous materials. In Phase II of the project, we will apply the technology developed in Phase I to the detection of other common foodborne bacterial contaminants. We will also extend our working relationship with academic laboratories to further test the device. We will work with diagnostics companies to determine their willingness to commercialize this technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD VOLUME AND VENOUS RETURN IN THERMAL STRAIN Principal Investigator & Institution: Mack, Gary W.; John B. Pierce Laboratory, Inc. 290 Congress Ave New Haven, Ct 06519 Timing: Fiscal Year 2002; Project Start 01-DEC-1977; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract): The overall aim of this renewal proposal is to uncover the mechanisms that underlie plasma volume expansion. They have developed two models to study these mechanisms. The human model, involving 32 min of intense exercise, produces a 10 percent plasma volume and albumin expansion within 24 hours. Their animal model, involving plasmapheresis, produces a complete recovery of both volume and albumin within 24 hours. The human and animal models differ from each other in certain respects but the two are sufficiently analogous to permit them to generate and test hypotheses in humans and then perform more invasive experiments to uncover mechanisms in rats. Using the human model they will test the following hypotheses related to the role of albumin synthetic rate, lymphatic protein transport and renal sodium handling in the process of plasma volume expansion: i) Sodium and water retention following saline loading is enhanced 24 hours following intense exercise. ii) Increased sodium retention following intense exercise occurs within both the proximal and distal tubules. iii) Enhanced sodium and water retention following intense exercise is mediated by changes in renal hemodynamics. iv) The elevation in plasma albumin content within the first two hours following intense exercise is mediated by increased lymphatic flow and thus modulated by changes in lymphatic outflow pressure. v) Albumin synthetic rate following intense exercise is modulated by posture dependent changes in circulating stress hormones. Using the animal model, they will test the following hypothesis: i) Increased hepatic albumin mRNA following chronic plasmapheresis is mediated by increased expression of hepatic nuclear transcription factor 1. ii) The primary mechanism for increased albumin content following plasmapheresis is lymphatic delivery of albumin to the vascular space. These studies characterizing the mechanisms underlying increased albumin synthesis and increased renal sodium reabsorption following exercise in humans and plasmapheresis in in vivo animal models will provide insight into the mechanisms underlying volume restoration. Such knowledge will lead to the development of methods to volume-expand compromised individuals more effectively without transfusion. Employment of both human and animal models enables the testing of hypotheses that are both relevant and mechanistic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIOVASCULAR DISEASE IN THE PIMA INDIANS Principal Investigator & Institution: Howard, Barbara V.; President; Medstar Research Institute Hyattsville, Md 20783 Timing: Fiscal Year 2002; Project Start 30-SEP-1988; Project End 31-MAY-2005 Summary: MedStar (formerly Medlantic) Research Institute proposes to continue its participation in the Strong Heart Study to manage the Arizona field center and the core laboratory. For the field center, this proposal describes methodology for 1) morbidity and mortality surveillance of the original Strong Heart Study cohort (1099 surviving out of 1500 original men and women ages 45-74 years in Phase I); 2) recruitment and examination of 30 families of at least 30 members, each 15 years and older; and 3) reexamination of the 900 family members from the Phase Ill pilot study. The Arizona field center comprises three American Indian communities: Gila River, Salt River, and Ak Chin. The Arizona center had a 71% recruitment rate in Phase I and 90%+ completion rates in Phases II and III. Morbidity and mortality surveillance obtained data on 99% of the participants. The core laboratory will provide accurate, reliable, stable, and comparable phenotypic measures of coronary heart disease risk factors in blood and urine samples. Measurements to be made for the family cohort include lipoprotein profile, glucose, HbA1c, insulin, LDL size, fibrinogen, PAI-1, apoE phenotype, apoB, apoA1, chemistry profile, and urinary albumin and creatinine. In addition, some exciting new markers of evolving importance in the etiology of atherosclerosis will be evaluated on stored baseline samples using a case-cohort design. sVCAM and endothelin-1 will be measured in approximately 400 definite cardiovascular disease cases and suitable controls. TSH also will be measured in these samples to allow evaluation of its role in cardiovascular disease in American Indians. The core laboratory will store blood, urine, and DNA in a safe and organized manner for effective inventory so that the resources will be retrievable for other scientists and the American Indian communities. Laboratory performance during the previous exams has been excellent, with high completion rates and precision and accuracy exceeding those of most core laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CASA PIA STUDY OF DENTAL AMALGAMS IN CHILDREN Principal Investigator & Institution: Derouen, Timothy A.; Professor and Chairman; Dental Public Health Sciences; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: This proposed project is a competing renewal to the Casa Pia Study of the Health Effects of Dental Amalgams in Children, a cooperative agreement funded by the National Institute of Dental and Craniofacial Research as one component of the Children's Amalgam Trial. The University of Washington is the applicant organization with a subcontract to the University of Lisbon, Portugal, as the clinical site. The Study is a randomized clinical trial in which 507 children of ages 8 to 10 at entry with substantial dental treatment needs and who are students of Casa Pia Schools in Lisbon, have been randomized to the use or non-use of mercury amalgams in their dental treatment. The project is currently in the second year of follow-up, with 95% retention thus far in the study. Mercury exposure is measured from urine samples at baseline and follow-up exams at one-year intervals. Four primary endpoints are monitored from baseline at one-year intervals: three neurobehavioral (combined assessments from neurobehavioral tests for attention, memory, and motor/visual motor domains) and one neurological
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(nerve conduction velocities). Secondary endpoints include two renal (two Glutathione Transferase isozymes specific to renal tubular damage), a clinical neurological exam, porphyrin profiles, urinary albumin levels and the occurrence of sentinel health events. Comparison between the two groups of children for the four primary endpoints are made annually using a combination of Hotelling's T2 test and an extension of the O'Brien test for multiple endpoints adapted for longitudinal data and multiple tests over time. If significant adverse health effects of exposure to dental amalgams (or to the alternative dental material, composites) are detected during the course of the study, the children treated with the harmful material will be re-treated with the other. The purpose of this renewal application is to extend the funding period to cover the seven years of follow-up proposed in the original grant. We intend to continue collecting data in the study po2ulation for the same four endpoints currently in use, with the same methodology as during the initial 3 follow-up years, utilizing the same personnel currently employed. in obtaining the data, with only some minor revisions in the neurobehavioral tests to account for the maturation of the test, population. The introduction of some new secondary endpoints is proposed. This international collaboration has resulted in a study team that has demonstrated its expertise in all relevant areas and its capability to successfully complete this important study and settle the controversy over whether amalgam has even any subtle health effects associated with its use in the most susceptible population, children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL AND PROTEIN REACTIONS WITH FOREIGN MATERIALS Principal Investigator & Institution: Horbett, Thomas A.; Professor; Chemical Engineering; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-JUN-1976; Project End 31-MAR-2005 Summary: The lack of knowledge of the mechanisms underlying the reactions of blood with polymeric biomaterials continues to be an obstacle to the design of better materials for use in contact with blood. Our hypothesis about these mechanisms can be stated generally as follows: a specific materials variable causes changes in the adsorbed protein layer that are responsible for changes in platelet adhesion and/or activation. For certain polyurethanes (PEUs), important specific materials variables are thought to be the alkyl chain length and density and the degree of surface enrichment of the fluorocarbon (FC) groups in FC PEUs. A systematic study of the effect of these materials variables on protein and platelet interactions will contribute to better understanding of blood reactivity with polymers. The specific aims are as follows: 1. The role of the adsorbed adhesion proteins fibrinogen, von Willebrand factor, fibronectin, and vitronectin in causing platelet activation will be determined using plasmas selectively deficient in the protein and a series of PEUs interacting with platelets under flow. Platelet activation will be characterized by measuring the ability of the adherent platelets to participate in platelet-platelet aggregate formation, the conversion of the platelets to the procoagulant state, and in situ measurement of intracellular calcium mobilization in platelets adhering under flow conditions. Dose-response studies of the effect of restoration of the deficient factors will also be done. 2. To test the hypothesis that the platelet activation by biomaterials is a function of both the amount and the state of adsorbed fibrinogen on each type of substrate, the activation of platelets deposited from flowing suspensions will be compared to the total amount and platelet recognizable fraction of fibrinogen on a series of polyurethanes. The platelet recognizability of the adsorbed fibrinogen will be characterized using monoclonal antibodies that bind to each of the putative platelet binding domains of fibrinogen. 3. A series of specially made polyurethanes (PEUs) with
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variations in chemical composition that should affect the adsorption and the biologic activity of the adhesion proteins and albumin will be used to test our mechanistic material hypotheses. PEUs with differences in side chain length, chain density, and chain type (CH2 or CF2) will be used. PEUs exhibiting low platelet adhesion despite the presence of relatively high amounts of adsorbed fibrinogen will be studied in greater depth, since we believe understanding of the mechanisms by which fibrinogen's biological activity is altered by these materials can contribute to the intelligent design of improved biomaterials. Reference materials will be Biospan and NIH PE and PDMS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL OBESITY AND ALBUMIN EXCRETION IN TYPE 1 DIABETES Principal Investigator & Institution: Sibley, Shalamar D.; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (adapted from the application) In subjects with diabetes, microalbuminuria predicts end-stage renal disease (ESRD) and cardiovascular disease (CVD). Despite gains, many patients still progress to ESRD and diabetic nephropathy (DN) is the leading cause of ESRD. CVD is the leading cause of death and risk begins to accelerate with microalbuminuria. Central obesity syndrome, which appears to be present in some subjects with type 1 diabetes and many subjects with type 2, increases risk of CVD and elevated albumin excretion rate (AER). This proposal will define the roles of intraabdominal fat (IAF) and the renin-angiotensin system (RAS) in the development of elevated AER and dyslipidemia in subjects with diabetes through an observational cross-sectional study of a subpopulation (three Minnesota cohorts and the Seattle cohort) of the Epidemiology Interventions and Complications Study and an independently-recruited interventional weight loss study of overweight subjects with type 1 diabetes. Additionally, population studies will examine frequencies of the G-6A angiotensinogen variants in subjects with and without hypertension (HTN) and elevated AER. The specific aims of the project are: (1) to characterize the RAS and its relationship to elevated AER, gender, and IAF (as measured by abdominal CT) in subjects with type 1 diabetes; (2) to define the relationship between IAF, central obesityrelated dyslipidemia, RAS, and AER in subjects with type 1 diabetes; (3) to determine the frequency of the G-6A haplotype subdivisions in subjects with type 1 diabetes and determine the associations of those haplotypes with HTN and AER; and (4) to compare frequencies of the G-6A AGT genotype in the highest and lowest quartiles of diastolic blood pressures among subjects in the top quartile of weight gain on intensive therapy during the Diabetes Control and Complications Trial. These studies will define mechanisms underlying the relationship between central obesity and the earliest stages of DN, providing insights applicable to some subjects with type 2 diabetes and HTN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMOPREVENTION OF GREEN TEA POLYPHENOL ON LIVER CANCER Principal Investigator & Institution: Wang, Jia-Sheng; None; Texas Tech University Box 42013 Lubbock, Tx 79409 Timing: Fiscal Year 2003; Project Start 16-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The long-term goal of this revised application is to design effective prevention strategies for reducing the incidence of liver cancer in high-
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risk populations. Primary liver cancer, mainly hepatocellular carcinoma (HCC), is one of the most common cancers in Asia and Africa. The poor prognosis of this malignancy results in it being the third most common cause of cancer deaths in the world. Chronic infection with hepatitis B viruses (HBV) and dietary aflatoxin exposure are two major etiologic risk factors for HCC in high-risk areas. The great challenge in cancer prevention and control is how to manage those who have already been exposed to carcinogens, such as individuals who are HBsAg carriers and have long-term aflatoxin exposure. Chemoprevention has been proposed as the good tool to target these high-risk populations. Among various identified chemopreventive agents, green tea polyphenols (GTP) have been shown to be safe and high effective in inhibition of carcinogen-induced mutagenesis and tumorigenesis in bioassays and animal models for different target organ sites, including aflatoxin-induced liver tumors. The specific aims for this study are (1) to incorporate molecular biomarkers analysis for aflatoxin exposure, HBV infection, and oxidative DNA damage into an on-going randomized, double blinded, and placebocontrolled intervention trial of GTP in 1,800 residents who are double seropositive of HBsAg and aflatoxin-albumin adduct in Fusui County, Guangxi Zhuang Autonomous Region, People's Republic of China; efficacy of the chemopreventive trial will be determined by monitoring changes of levels of risk-factor specific molecular biomarkers and the actual incidence of HCC in the studied population. (2) to examine and assess the efficacy of GTP in reducing aflatoxin biomarkers by measuring aflatoxin-albumin adducts in serum and various aflatoxin biomarkers in urine collected from 300 participants in different time of the study. Difference in metabolic phenotypes/genotypes as they related to aflatoxin biomarker levels will be determined. (3) to evaluate the inhibitory effect of GTP on HBV-associated markers including HBVDNA replication and HBV-induced immunologic changes in serum samples. (4) to determine antioxidative role of GTP in inhibition of the level of 8-hydroxy-2'deoxyguanosine in urine samples collected from the study participants and (5) to determine and assess long-term bioavailability and biotransformation of GTP and the long-term toxicological effect of GTP on study participants. The results of this study would help to evaluate the chemoprotective effect of GTP against human HCC and to understand the molecular mechanisms of GTP in chemoprevention of human HCC caused by well-defined major risk factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC RENAL INSUFFICIENCY IN NAPRTCS PATIENTS Principal Investigator & Institution: Warady, Bradley; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This application, a joint effort of 26 centers of the NAPRTCS, is entitled "Chronic Renal Insufficiency (CRI) in NAPRTCS Patients. We will enroll 300 children (1-16 years) with measured glomerular filtration rates (GFR) of 25-75 mL/min/1.73m2. Follow-up with annual GFR and 6 month physical examinations and determinations of hemoglobin, electrolytes, serum, albumin, serum calcium, serum phosphorus, parathyroid hormone and urinary indices will test the 1st hypothesis that this cohort will most accurately define the rate of and the risk factors for progression of CRI, and that this progression will be correlated with proteinuria, albumin, blood pressure, nutritional status, growth and hyperparathyroidism. To test the 2nd hypothesis that cardiovascular disease develops in children with mild CRI and that its prevalence and severity increase in association with the progression of CRI, we will perform baseline and annual 24-hour ambulatory blood pressure monitoring,
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echocardiographic assessments to determine left-ventricular mass and LV function, and B-mode ultrasound of the carotid artery to determine the IMT and carotid artery compliance. To test the 3rd hypothesis that the neurocognitive outcome of children with CRI is influenced by the progression of renal insufficiency, a battery of validated neurocognitive tests will be conducted at study entry and at 6, 12 and 24 months to assess many cortical and subcortical areas of brain function. To test the 4th hypothesis that chronic inflammation contributes to cachexia, growth hormone resistance and growth retardation, we will examine the impact of circulating cytokine and neuropeptide concentrations on dietary intake, nutritional and growth parameters as well as growth hormone axis pertubations and responsiveness to growth hormone therapy. Finally, to test the 5th hypothesis that a correlation exist between bone histology, serum concentration of PTH and measured GFR, we will measure and characterize the biochemical and histologic features of renal osteodystrophy and determine the serum concentrations of PTH that are associated with normal rates of bone formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COAT-PLATELETS Principal Investigator & Institution: Dale, George L.; Associate Professor; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: Platelets co-stimulated with collagen and thrombin display a number of unusual features. As initially described, these dual activated platelets, referred to a COAT-platelets (collagen and thrombin stimulated-platelets), express high levels of surface-bound factor V. This sub-population of platelets represents approximately 30 percent of the total and is most prominent among young platelets. COAT-platelets are also observed upon activation with thrombin plus convulxin, an agonist for glycoprotein VI; however, no single agonist examined was able to produce COATplatelets. The functional significance of FV on COAT-platelets was shown by demonstrating high factor V activity, preferential binding of factor Xa and significant prothrombinase activity. In addition, COAT-platelets were found to have several other alpha-granule proteins including von Willebrand factor, fibrinogen, fibronectin, thrombospondin and alpha2-antiplasmin, bound at high levels. Unexpectedly, COATplatelet formation is prevented by transglutaminase inhibitors including dansyl cadaverine, putrescine, and acetyl-casein, and a synthetic peptide substrate for transglutaminases is incorporated in COAT- platelets. The platelet component serving as the acyl acceptor for the transglutaminase reaction was found to be serotonin, and multi-valent serotonin-adducts of albumin were effective inhibitors of COAT-platelet formation. Fibrinogen isolated from COAT-platelets was also found to have conjugated serotonin. This proposal will further characterize COAT-platelets by identifying serotonin-adducts of other alpha-granule proteins found on COAT- platelets, by characterizing the serotonin binding sites present on COAT-platelets, and by evaluating the physiological manipulation of COAT-platelets in experimental animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COPPER/ALBUMIN REDOX-CYCLING IN PREECLAMPSIA Principal Investigator & Institution: Kagan, Valerian E.; Professor; Environ & Occupational Health; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
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Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): The central hypothesis is that during preeclampsia increased free fatty acids bound by albumin and/or modification of Cys34 impair normal albumin/copper interactions in such a way that 'loosely-bound" copper is capable of catalyzing redox cycling resulting in the generation of reactive oxygen species. The first goal is to establish that changes in copper/albumin interactions can trigger copper-dependent redox cycling and oxidative stress in preeclampsia. Using plasma obtained from preeclamptic and normal pregnant women, the investigator will 1) establish that preeclamptic plasma contains enhanced potential for generating copperdependent oxidative stress and 2) determine the role for free fatty acids and thiol oxidation/nitrosylation of albumin in mediating this enhancement. The second goal is to use a simple model system utilizing purified human serum albumin to define the molecular mechanisms for free fatty acid and Cys34 modification of copper/albumin interactions and redox cycling. The third goal is to determine whether enhanced redox cycling of copper/albumin can alter the vascular behavior by: 1) demonstrating the potential of preeclamptic plasma to alter vascular function in mesenteric arteries from pregnant mice, and 2) establishing that free fatty acid and Cys34, modification of albumin can result in copper-dependent alterations in vascular reactivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--TISSUE /BIOPHYSICAL Principal Investigator & Institution: Hassoun, Paul M.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 07-FEB-2003; Project End 31-JAN-2008 Summary: The tissue culture/biophysical Core in this program project serves three key roles in this PPG and is a key mechanism for integrated collaboration between the projects. First, the Core will provide a centralized resource facility for eight lung endothelial cell cultures used in each of five projects. Specifically, the cell culture core will continue provide freshly isolated and cultured murine lung endothelial EC, cell lines of human and bovine pulmonary artery EC, human and bovine pulmonary microvascular EC, human dermal microvascular EC, native cell lines and cell lines overexpressing wild type or tyrosine-deficient mutant of protein tyrosine phosphatase mu, and rat fat pad microvascular cells over-expressing protein kinase C-delta. Second, this Core will utilize sophisticated state of the art technologies to carefully expose lung pulmonary endothelium in mechanically active settings relevant to physiological and pathophysiological in vivo conditions. Important tools for this work include culturing EC under conditions of controlled cyclic stretch and controlled laminar shear stress. Finally, the Core will quantitate the physiological significance of each of the studies proposed in the Program Project: (1) measurements of albumin clearance across confluent EC, (2) measurements of trans-monolayer electrical resistance of static cultures and cyclic stretch-preconditioned EC monolayers using endothelial cell-substrate impedance sensing system (ECIS); (3) real time simultaneous measurements of EC transendothelial electrical resistance under shear stress; and (4) EC wound assay with real time monitoring of EC wound healing using ECIS lectroporation/wounding module. The extensive experience of the biophysical and tissue culture core personnel continue to function as a tissue culture core (previous Program Project Grant HL-58064) assuring the continuous supply of high quality cells, culturing cells under precisely characterized conditions of shear stress or cyclic stretch and expert assistance in quantitation of EC monolayer barrier function. The close proximity of the tissue culture and biophysical facilities will provide reproducibility and consistency of results obtained in the Program
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Projects, and ensure the most economical use of the Core to adequately supply all the investigators of the Program Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETECTION ATHEROSCLEROTIC P
AND
MODULATION
OF
VULNERABLE
Principal Investigator & Institution: Ganz, Peter; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Episodes of instability caused by plaque disruption frequently punctuate the course of stable coronary atherosclerosis. Pathological studies have identified critical features of lesions vulnerable to rupture (large lipid pool, prominent inflammatory component and thin fibrous cap) but routine testing including diagnostic angiography fails to identify these important structural features of vulnerable plaques. We aim to develop and validate in atherosclerotic rabbits and in humans, high resolution intravascular magnetic resonance imaging to identify the tissue characteristics of atherosclerotic plaques. The inflammatory component of the plaques will be delineated by the use of contrast agents that are selectively taken up by macrophages (particles of ultrasmall superparamagnetic iron oxide) or contrast agents that localize to sites of increased vascular permeability (gadolinium-labeled albumin)-classical characteristics of atheroma formation. We will use high resolution intravascular magnetic resonance imaging to characterize changes in plaque features and their time course using cholesterol lowering as a well-established intervention. We will test the hypothesis in humans, with parallel validation in rabbits, that intensive cholesterollowering can rapidly improve the high risk morphometric characteristics and the inflammatory component of plaques, thereby leading to rapid stabilization. Future extensions of this work might use the technologies validated now to test similar hypotheses with novel therapeutic agents that have a putative direct effect on atherosclerotic lesions. These projects are considered the necessary cornerstone for examining the effects in humans of new therapeutic strategies. These studies provide novel approaches to detection and characterization of vulnerable atherosclerotic lesions in patients. This much needed information cannot be obtained with conventional angiography or with other current clinical means of testing. This work should provide new mechanistic insights and promote development and evaluation of therapeutic strategies for further protection from plaque rupture, thrombosis and fatal coronary events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT AND EVALUATION OF EXPOSURE BIOMARKERS PAHS, PHIP AND AROMATIC AMINES Principal Investigator & Institution: Tannenbaum, Steven R.; Professor/ Director; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 07-APR-1993; Project End 31-MAY-2007 Summary: (provided by applicant): The long-term objective of this Project is to develop molecular biomarker strategies that are based on DNA and protein adducts and reveal exposure to carcinogens and their biologically effective dose in people. The hypothesis driving the research in this Project is that levels of specific biomarkers define exposure and biologically effective dose in susceptible individuals. The strategies will employ laser-induced fluorescence (LIF) for high performance liquid chromatography (HPLC)
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detection, with and without derivatization labeling, and mass spectrometric technologies, including electrospray HPLC-tandem mass spectroscopy (HPLC-MS-MS). Accelerator mass spectrometry (AMS) will be an important new technology introduced into the Program Project to facilitate the early-stage tracer experiments necessary for adduct identification and structure elucidation. This Project is designed to develop the advanced exposure assessment methods needed to discern hazards for human populations where ambient exposure levels are low, but the toxicologic hazards of these exposures remain high. The classes of agents under investigation include PAHs, heterocyclic aromatic amines (HAAs) associated with cooked foods, and aromatic amines. Serum albumin adducts of benzo[a]pyrene, B[a]P, one of the hydrocarbons, will be determined in human population studies using advanced HPLC-LIF methods to assess its role in human cancer. The structure of albumin adducts of PhIP, a prominent cooked-food carcinogen, will be determined and the adducts will be validated as exposure biomarkers. HPLC-LIF and MS methods for PhIP and aromatic amine DNA adducts will be developed and validated. Biomarker investigations of specific alkylanilines associated epidemiologically with bladder cancer will be undertaken to confirm their biological role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TECHNIQUE
DEVELOPMENT
OF
A
NOVEL
GAS
EMBOLOTHERAPY
Principal Investigator & Institution: Bull, Joseph L.; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): The delivery of emboli to arterial blood flow with the goal of flow occlusion, or embolotherapy, is a potential means to treat a variety of cancers, such as heptatocellular carcinoma (HCC) and renal carcinoma. HCC, the most common form of liver cancer, occurs in 2-30 per 100,000 males each year, resulting in approximately 1,250,000 deaths worldwide annually. The accompanying liver cirrhosis makes the treatment of HCC by traditional methods difficult. Systemic chemotherapy has no appreciable impact on survival rates. In addition to these types of cancer, many other types could potentially be treated using embototherapy. Previous attempts at embolotherapy have used solid emboli, such as blood clot, gelatin sponge, particulates, balloons and streamers. A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor, i.e. minimizing ischemia of healthy tissue, without extremely invasive procedures. Here, we propose an acoustically activated gas embolotherapy. While gas bubbles have been used as ultrasonic contrast agents, they have not previously been used to occlude flow to tumors. Moreover, this novel approach involves introducing liquid droplets, which are small enough to pass through capillaries, into the vascular flow. The droplets could be tracked using ultrasound and vaporized via high intensity ultrasound near the tumor allowing gas bubbles, which are considerably larger than the liquid drops from which they originated, to occlude flow in the tumor. This minimally invasive technique would allow selective delivery of gas emboli to the tumor, and is well suited to repeated doses and long term use. The proposed research uses computational and experimental (animal and bench top) studies to provide proof of concept of this technique. This work will investigate the physical phenomena of vessel occlusion by gas emboli and vessel deformation due to the vaporization of liquid droplets. The proposed research is a collaboration of engineers, physicists, and clinicians with expertise in expertise in fluid dynamics, gas transport, and diagnostic and
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therapeutic ultrasound. The proposed research is an essential first step in developing this potentially revolutionary technique. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMICS OF FLOW-DEPENDENT ARTERIAL PERMEABILITY Principal Investigator & Institution: Friedman, Morton H.; Professor; Biomedical Engineering; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-MAR-2004 Summary: The overall objective of this research is to understand the factors affecting the transendothelial entry of macromolecules into the arterial wall, and particularly the mediation of this process by local hemodynamics. The interest in macromolecular transport is prompted by its importance in the genesis and development of artherosclerosis. The mediation of arterial uptake by hemodynamic factors is of particular interest because the distribution of atherosclerotic lesions suggests that hemodynamic factors may be involved in the localization of the disease; furthermore, there is evidence that hemodynamic stress can influence endothelial permeability. A primary hypothesis of this research is that an important fraction of the transendothelial flux occurs during increases in permeability prompted by changes in flow; accordingly, particular emphasis is placed on the dynamic response of the barrier function of the endothelial lining to changes in the hemodynamic environment. The research objectives are addressed through a unique combination of animal experiments, computer simulation and cell and molecular biology. The spatial variation of the albumin permeability in the eternal iliac arteries of swine, either at baseline or subsequent to interventions that alter flow, will be obtained using photographic densitometry of Evans Blue dye to measure albumin uptake. The alterations in flow will be produced by reversible, adjustable femoral arteriovenous shunts. The distribution of wall shear stress, and of the changes in stress caused by manipulating the shunt, in the iliac vessels will be obtained from validated fluid dynamic computations in regions derived from injection casts of the arteries and the proximal vasculature; the dependence of albumin uptake on hemodynamic stress, and alterations in stress, will be assessed and modeled. In a separate set of animals, casting material will not be injected, and tissue from the region of interested will be fixed or explanted and cultured, and a variety of techniques will be used to relate the variations in permeability to cellular properties. Of particular interest are properties that mediate the redox state of the cell, the integrity of the cytoskeleton, and its junctions with neighboring cells and adhesion to the substratum. The effects of hypercholesterolemia on vascular permeability and its dynamic response to changes in flow will be examined as well, to determine whether high lipid levels potential the effects of flow changes on vascular uptake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCED PRIMARY REPAIR OF LIGAMENT INJURIES Principal Investigator & Institution: Murray, Martha M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Over 100,000 people rupture the anterior cruciate ligament (ACL) of the knee each year. The current best treatment, replacement of the ligament with a graft of tendon, does not replace the complex architecture and biomechanics of the original ligament, and as many as 50% of patients will have signs of arthritis at only 7 years after surgery. Because of the clinical importance of this injury
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and the lack of an optimal treatment method, I have become increasingly interested in developing new approaches to ACL injuries, and have spent the last five years working to combine a career conducting basic investigations in ligament healing with clinical practice as an orthopaedic surgeon. During that time, I have published seven firstauthor peer reviewed publications, served as the principal investigator on three grants, won three national awards for ligament research, spoken at national conferences and served as a reviewer and book section editor. The specific aims of this career award are to gain independence in several specific cellular and molecular assays, scaffold manufacture, the use of in vivo animal models and statistical analysis through coursework, seminar attendance and training in well-established laboratories. The acquisition of these skills will enhance my ability to serve as an independent scientist by lessening my current dependence on collaborators in these areas. This research proposal focuses on developing a new method of treatment for ACL rupture: enhanced primary repair. This technique makes use of a provisional scaffold to supplement a primary ligament repair and encourage healing in the gap between the ends of the ruptured ACL. This procedure could potentially restore the architecture and biomechanics of the knee, while maintaining the proprioceptive function of the ACL, thus potentially decreasing the risk of post-operative instability and osteoarthritis. The first specific aim is to define the cell and tissue events in the ACL after injury and the changes in these events after placement of a bioadhesive scaffold in the ACL defect. In the second aim, in vitro assays will be conducted to define the composition of a provisional scaffold which best stimulates ACL cells to mimic the MCL healing process. In the third aim, the optimized scaffolds will be tested in an in vivo canine ACL non-union model. Information gained in each of these aims will serve to improve our understanding of mechanisms of ligament healing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF HEPATOCELLULAR HEPATITIS B VIRUS IN 3 POPULATIONS
CARCINOMA
&
Principal Investigator & Institution: London, W. Thomas.; Senior Member; Fox Chase Cancer Center Philadelphia, Pa 191112434 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Applicant's Description) Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa revealed a 14-fold greater death rate from hepatocellular carcinoma (HCC) among the Haimen (168 per 100,000) than the Senegalese cohort (12 per 100,000). Even though chronic infection with hepatitis B virus (HBV) is the major risk factor for HCC in both populations, the age-adjusted prevalence of chronic infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, is also similar or greater in the Senegalese population. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life, however, is much higher among the Chinese than the Senegalese population. Nevertheless, within the Chinese cohort, viremia at study entry is not a risk factor for HCC after four years of follow-up. The aims of this project focus on factors that may account for variation in HCC risk in the Chinese and Senegalese cohorts and a cohort of Asian-American HBV carriers living in the Philadelphia area. Continued tracking of these three cohorts will test the hypothesis that with longer duration of follow-up, H B V v iremia and liver damage at study entry are associated with person-specific risks of HCC and that aflatoxin-B1 (AFB1)-albumin adducts are a s s ociated with development of HCC among viremic individuals and/or genotypically determined poor detoxifiers of AFB1 (in collaboration with Project 2). In close cooperation with the studies of WHV in
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woodchucks (Project 3), an intensive longitudinal study of 1000 male and female HBV carriers in these three populations will be conducted to: a) examine whether perturbations of the stability of HBV serum markers are associated with acute illnesses, aflatoxin exposure, and/or outgrowth of viral mutants; b) assay hepatocyte turnover and immune responses in liver biopsies; c) correlate these measures with viral load; d) examine the relationship of sex differences in changes in HBV serum markers over time to the lower HCC risk of female HBV carriers. Because present studies show that an episode of acute hepatitis in adulthood approximately doubles HCC risk among both HBV carriers and non-carriers, the causes and outcomes of 200 cases of acute hepatitis in Haimen City will be characterized. This research will lead to a new level of understanding of the factors that lead to HCC and to new strategies for the prevention of this lethal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDIDYMAL MATURATION OF SPERM SIGNALING PATHWAYS Principal Investigator & Institution: Gerton, George L.; Research Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: The long-term goals of the Principal Investigator and the Foreign Collaborator are to understand the molecular basis of sperm fertilization competence. The PI has focused in his research on the signal transduction mechanisms underlying sperm capacitation, which requires a maturation process that occurs during their transit through the epididymis. The foreign investigator has studied the biochemistry and cell biology of epididymal maturation. Together, these investigators have demonstrated an apparent maturation of the signal transduction mechanisms in parallel with epididymal maturation. The aims of this proposal are to 1) determine whether sperm epididymal transit is associated with alteration of cholesterol efflux in response to serum albumin and beta cyclodextrins, agents that bind cholesterol in vitro, 2) determine the mechanisms by which epididymal maturation regulates the response of the sperm to dbcAMP leading to protein tyrosine phosphorylation, and 3) determine whether the oxidation state of the epididymal environment can influence the maturation of the signal transduction machinery that regulates sperm capacitation. The results of these experiments may aid in the understanding of epididymal maturation and its role in fertilization competence, which may relevant to both male infertility and contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ETHANOL EFFECTS ON LIVER IN SELF-ADMINISTERING PRIMATES Principal Investigator & Institution: Cunningham, Carol C.; Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Most protocols that employ animal models for studying the development of alcoholic liver disease utilize the rat that is being administered ethanol as part of the diet. These models have provided much of the information we presently have on the mechanisms that contribute to development of liver damage associated with alcohol abuse. To date there are no animal models where voluntary ethanol consumption has led to irreversible liver damage; i.e., damage past the fatty liver stage. The studies proposed in this application are designed to determine if non-human primates that are self-administering ethanol will demonstrate liver
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pathology predictive of the development of alcoholic hepatitis and fibrosis. Eleven Macaca fascicularis monkeys will be given free access to ethanol in drinking water for 1 year. These animals have been previously trained to drink ethanol voluntarily and some have consumed up to 4g/kg/day, which is equivalent to 16 drinks a day by a human. The heavier drinkers averaged blood ethanol concentrations of 170 mg/dl in a previous protocol. In the proposed studies, light, moderate and heavy drinkers will be included, which are comprised of 6 females and 5 males. Evidence for liver damage will be sought by analyses of blood samples, which will include measurements of yglutamyltransferase, aspartate and alanine transaminases, bilirubin, albumin, globulin and other blood components. Urinary concentrations of isoprostanes will be measured to screen for ethanol-related oxidative stress. Liver needle biopsy samples, taken every 3 months, will be examined by light and electron microscopy for indices of liver damage, such as hepatocyte ballooning, Mallory body formation, inflammation and fibrosis. lmmunohistochemical analyses will be implemented to measure levels of inflammation, apoptosis and stellate cell activation. The objectives of this study are 1) to determine if the self-administering M. fascicularis will develop liver pathology past the fatty liver stage and 2) to evaluate the efficacy of using blood and urine samples to follow development of alcoholic liver disease in an animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FATTY PRODUCTION
ACID
REGULATION
OF
LIVER
LIPOPROTEIN
Principal Investigator & Institution: Ginsberg, Henry N.; Professor; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Lipotoxicity involves the excess delivery of fatty acids (FA) to sites other than adipose tissue. In vivo, fatty acids (FA) can arrive at the liver bound to albumin or as components of TG (TG)-enriched remnant lipoproteins (chylomicron and VLDL). In the latter instances, FA can be liberated from remnants by the action of hepatic lipase bound to capillaries in the hepatic vascular bed or released from lysosomes after receptor-mediated internalization of remnant lipoproteins. In addition to exogenously derived FA, increased availability of FA may result form their synthesis in the liver from acetylCoA via lipogenesis. The latter pathway has been linked recently to insulin resistance and hyperinsulinemia. The liver is unique in that it is able to "unload" excess FA in bulk form by assembling and secreting apoBlipoproteins. There are few data, however, concerning the effects of FA from each of the sources described above on the two-step process of apoB-lipoprotein assembly: the first step involves the targeting of nascent apoB across the ER membrane and assembly of a lipid-poor primordial lipoprotein, while the second step involves the bulk addition of core lipid to the primordial particle and the formation of the mature TG-rich apoBlipoprotein. Importantly, it is not known if each of the pathways involved in providing increased FA within the hepatocyte impacts equally on FA synthesis and oxidation, genes involved in TG synthesis, or genes involved in the assembly and secretion of apoB-lipoproteins. The link between insulin resistance/hyperinsulinemia and increased VLDL secretion is also incompletely defined. In particular, the relative importance of hepatic lipogenesis versus plasma FA uptake by the liver in the increased apoBlipoprotein secretion observed in insulin resistant animal models and humans has not been studied. The experiments proposed in this project are directed at unanswered questions related to FA regulation of apoB-lipoprotein assembly and secretion, including: (1) the effects of plasma albumin-delivered FA on each of the steps in apoB-
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lipoprotein assembly and the expression of genes involved in maintaining hepatic lipid homeostasis; (2) the effects TG-rich remnant-like particle-delivered FA on apoBlipoprotein assembly and gene expression; and (3) the relative importance of insulin resistance/hyperinsulinemia versus increased plasma FA availability in the reaulation of apoB-lipoprotein assemblv and secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALSIS OF CELL TYPE SPECIFIC FUNCTIONS Principal Investigator & Institution: Fournier, Raymond E.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-MAR-2003 Summary: The long-term goal of this research is to understand the regulation of tissuespecific gene expression in mammalian cells. Using cultured hepatoma cells, hepatoma hybrids, and somatic variants as genetic tools, mechanisms that control expression of specific liver genes in hepatic and non-hepatic cells will be defined. Three main areas of research will be pursued. First, genetic experiments will be performed to dissect the extinction phenotypes of intertypic hepatoma hybrids. Hepatoma x fibroblast hybrids and microcell hybrids will be used to define genetic factors involved in the extinction process, and both monogenic and polygenic extinction phenotypes will be explored. In other experiments, the role of transactivator repression in extinction of specific target genes will be assessed by analyzing the phenotypes of hybrids that coexpress one or more cell-specific genes. Hepatoma variants with defects in expression of specific liver genes will also be isolated and characterized, and their phenotypes will be studied by complementation and transfection. Second, mechanisms of transgene extinction will be analyzed, and DNA elements involved in extinction will be defined. Hepatoma transfectants containing stably integrated, position-independent transgenes will be isolated and characterized, and expression of transgene sequences will be monitored in transfectant x fibroblast hybrids. These experiments will identify regulatory elements involved in both position- independent expression and extinction, and they should clarify the connection between chromatin structure and the extinction process. Third, the regulation of chromosomal alleles that have been specifically modified by homologous recombination will be studied. Efficient homologous modification of the human apolipoprotein B and alpha1-antitrypsin genes will be accomplished using novel, recombinationproficient chicken/human microcell hybrids, and the functions of the altered alleles will be assessed after transfer of the modified human chromosomes to expressing and non-expressing mammalian cells. These studies should help define mechanisms of eukaryotic gene control, and they may provide insights into perturbations of those controls that occur in abnormal development and neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC EPIDEMIOLOGY OF HYPERTENSION IN AFRICAN AMERICAN Principal Investigator & Institution: Rotimi, Charles N.; Associate Professor and Director; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-JUL-2006 Summary: The goal of this project in genomic research is to contribute to the growing attempts to fill a major void in resources available to the research community for dissecting the pathophysiology of hypertension (HTN) and related complications in African Americans. It is well documented that A experience one of the highest incidence
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of HTN in the world. Epidemiologic studies have demonstrated the important role of environmental factors including diet (e.g., high salt intake), lifestyle (e.g., lack of physical activity) and psycho-socio stressors (e.g., employment difficulty) in the etiology of HTN. However, a proportion of the total variance remains unexplained. Because of the importance of family history and observed differential susceptibility to HTN, it is now widely accepted that the etiology of HTN is the result of complex interplay of genetics and the environment. Based on an on-going family study, we propose to recruit a population of 350 AA families with 5 or more members (n> 1,750 persons) in Washington, DC. During a clinical exam, we will collect demographic data, measure BP, height, weight, fat mass, fat free mass, waist and hip circumference. Blood will be drawn for assays of physiologic intermediates including components of the renin-angiotensin aldosterone system (RAAS-Angiotensinogen-AGT, angiotensin-converting enzyme aldosterone system (RAAS-Angiotensinogen-AGT, angiotensin-converting enzyme-ACE and aldosterone), endothelin 1, C-reactive protein (CRP), sodium potassium, calcium, albumin, creatinine, glucose, insulin and leptin. Genomic DNA will be extracted. We propose to evaluate the association and linkage between BP, HTN and genes of the RAAS (ACE, AGT and angiotensin II receptor type 1), epithelial sodium channel beta subunit, endothelial nitric oxide synthase, CRP, endothelin 1, and beta2-adrenergic receptor. We will evaluate single nucleotide polymorphisms (SNP) variations in candidate genes and determine if variation in each SNP and in constructed haplotype, explain variations in BP and HTN risk. In addition, DNA will be stored for future application to conduct genome-wide scan with the goal of identifying novel genomic regions in linkage and association with BP and HTN in AA. Identified novel genomic regions may inform our understanding of the etiology of HTN in other human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC REGULATION OF 03-INDUCED INFLAMMATION Principal Investigator & Institution: Foster, W Michael.; Research Professor; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Laboratory studies have demonstrated that short-term single exposure of adult humans to ambient levels of O3 leads to inflammation of the airway. Lung inflammation is observable 3-18 hr after exposure, and is not correlated to the functional changes that arise during exposures or slowly dissipate during recovery, 1-2 hr postexposure. The inflammation is characterized by an influx of polymorphonuclear leukocytes and increases in total protein, albumin, pro-inflammatory cytokines, and granulocyte-macrophage colony-stimulating factor in bronchoalveolar lavage fluid. Significant inter-individual variation in the inflammatory response is found among otherwise homogeneous subjects suggesting that intrinsic host factors contribute to the magnitude of beta3-induced lung injury. Further, although ambient exposure to beta3 is frequently intermittent, whether the severity of inflammation increases upon reexposure remains controversial. Thus, basic questions remain: 1) is the inter-individual nature of the inflammatory response to O3 explained by host factors, i.e., genetic background, and 2) do inflammatory airway responses in sensitive subjects adapt upon re-exposure to O3? Understanding the mechanisms intrinsic to O3-induced airway inflammation is essential for predicting host susceptibility and risk of lung and epithelial injury from exposure to O3. Our HYPOTHESIS is that specific gene polymorphisms/mutations contribute to differential susceptibility to O3-induced lung injury in healthy subjects and are host factors that regulate risk of exposure to O3. We
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will use a multi-disciplinary approach that applies physiologic and genetic techniques to a controlled human exposure system. Specific aims will determine: 1) the range in susceptibility of humans to develop airway inflammation and hyperpermeability after a single exposure to O3, and 2) if subjects differentially susceptible to ozone maintain their sensitivity during intermittent exposure to O3, and 3) the association of selected genetic markers with O3-induced lung injury and airway inflammatory responses. These investigations will help to establish genetic background as a host factor in the susceptibility of humans to O3 exposure and utility of genetic factors as biomarkers of lung injury induced by inhalable oxidants and environmental pollutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF KIDNEY DISEASE IN ZUNI INDIANS Principal Investigator & Institution: Zager, Philip G.; Professor; Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The Zuni Pueblo, in NM, is home to a small, geographically isolated, tribe, which has been relatively endogamous for hundreds of years. The Zuni Pueblo is currently experiencing a major epidemic of renal disease. This epidemic, unlike those in other American Indian communities, is attributable to high rates of diabetic and non-diabetic renal disease. Mesangiopathic nephropathy, most commonly IgA nephropathy (IgAN), comprises the majority of non-diabetic renal disease. Almost everyone at Zuni has a relative with renal disease, leading to strong community support for collaborative research. This has created a unique opportunity to identify genetic and environmental factors that modulate the susceptibility to renal disease and intermediate phenotypes. To maximize this opportunity, we established the, NIDDK funded, Zuni Kidney Project (ZKP). We have conducted a population-based survey of Zuni residents 5 years of age. We have ascertained family structure, quantified glycemic control, proteinuria, and renal function, and isolated DNA in over 1,650 participants. The ZKP is participating in FIND, a NIDDK funded sib pair-based consortium charged with identifying diabetic nephropathy susceptibility genes. However, the study design and ascertainment criteria in FIND do not take advantage of the unique population structure of Zuni. This has limited the ZKP's involvement in FIND and led to under-utilization of this unique resource. The present application requests support to conduct a study of extended families to identify genomic segments that modulate susceptibility to diabetic and non-diabetic renal disease and intermediate phenotypes. We will identify risk factors that show the strongest evidence for single gene effects and map those genes to specific chromosomal regions. Our investigative team includes the Zuni Pueblo, University of New Mexico Health Sciences Center (UNMHSC), and Southwest Foundation for Biomedical Research, and Strong Heart Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS OF NEPHROPATHY IN HUMAN TYPE 2 DIABETES Principal Investigator & Institution: Elbein, Steven C.; Professor; Internal Medicine; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2004 Summary: Fewer than 30 percent of diabetic patients get irreversible nephropathy. For diabetic relatives of patients with nephropathy the risk is 3.5 to 10-fold higher than the general population. Thus, genetic susceptibility appears to distinguish those diabetic
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patients destined to develop nephropathy. We propose to map diabetes susceptibility genes using an approach that combines nonparametric sib pair analysis of concordant and discordant sibs, allelic association, and quantitative trait analysis in families with multiple diabetic siblings. Linkage will be tested in 150 sib pairs concordant for diabetes and 75 discordant for diabetes. Linkage and association will first be tested for known genes and proposed loci that influence risk of Type 2 diabetes, hypertension, nephropathy in other populations or animal models, and glycemic effects including aldose reductase. A 10 cM genome scan will be conducted to map novel genes. Potential nephropathy loci will be tested for association in 200 unrelated patients with nephropathy, and tested in an additional 100 concordant and 50 discordant sib pairs. Additional studies will map the quantitative trait locus controlling albumin excretion in diabetic patients using a variance component approach to linkage. Finally, transformed lymphocytes from diabetic and nondiabetic members of familial diabetes pedigrees will be studied under euglycemic and hyperglycemic conditions to search for preclinical markers of nephropathy. These studies will be conducted in families for which a genome search for diabetes susceptibility is in progress. Sorbitol accumulation and aldose reductase expression will be examined and tested for linkage to the aldose reductase locus. Sodium hydrogen exchange will be measured and tested for correlation with sodium hydrogen exchanger 1 message. A genome scan will be undertaken to map the quantitative trait locus controlling sodium hydrogen exchange, and to determine whether this locus leads to nephropathy. These studies will identify genes and chromosomal regions containing genes that predispose to nephropathy, and will lead to an improved understanding better management of diabetic nephropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEALTH EFFECTS OF DENTAL AMALGAMS IN CHILDREN Principal Investigator & Institution: Mckinlay, Sonja M.; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: The safety of silver amalgam as a dental restorative material has been controversial since its introduction 150 years ago, but-until recently it has been generally assumed that the exposure to mercury from dental amalgam is limited to the acute placement phase. Some recent studies (mostly observational and primarily of adults) have demonstrated chronic release of mercury vapor from amalgam fillings during chewing and brushing, raising new safety concerns. The randomized trial, Children's Amalgam Trial (CAT) is designed as a comprehensive assessment of the relative safety of silver amalgam, compared to the alternate, mercury-free materials, demonstrating equivalence of cognitive and renal outcomes. Children aged 6-10 at last birthday with no prior dental restoration (to minimize prior mercury exposure) and mixed (primary and permanent) dentition were recruited from two New England communities (rural Main and inner city Boston/Cambridge, Massachusetts) to represent, to the extent feasible, the likely effects in children in the US. Children were chosen for this trial as they are most likely to be amalgam-free at randomization and, given their smaller body mass and developmental stage, more likely to demonstrate adverse effects (if any) of increased body mercury burden. This 5-year competing continuation will enable completion of 6 years of observation of the trial subjects/randomized from August 1997 to September 1999). Current funding, through July 2001, will include two years of observation only. Given the obvious public health significance of the potential long range impact of mercury on cognitive function, the primary endpoint measure is the full scale IQ score of the Wechsler Intelligence Scale for Children: Third Edition (WISC III)
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Albumin
and the primary outcome is the estimated change in the score between Baseline and 6 years post randomization, adjusted for the baseline IQ score. Secondary outcomes include more immediately measured safety endpoints that will be monitored annually, including: urine mercury levels; a dip-stick screening test for urinary protein (confirmed by albumin level); and gamma-glutamyl transpeptidase (gamma-GTP). Other endpoints include other aspects of cognitive function from an extensive neuropsychological test battery, while key covariates include a measure of dietary mercury (hair levels) and the dose of amalgam summarized in "surface-years" of exposure. To date, 534 subjects have been randomized (107%) and follow-up through the 12 month visit, although not yet complete, indicates that the initial (12 month) response rate should be at least 92%. Subsequent losses are expected to be negligible (about 2% per year). A non- orthogonal analysis of covariance will test for equivalence on IQ scores between treatments arms similar modeling will be used to address secondary aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HGF IN LIVER DEVELOPMENT,REGENERATION AND NEOPLASIA Principal Investigator & Institution: Michalopoulos, George K.; Professor and Chairman; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-JUL-1983; Project End 31-DEC-2007 Summary: (provided by applicant) The main goal of the proposal is to understand the role of Hepatocyte Growth Factor (HGF), its receptor (cMet) and the hepatic biomatrix as determinants of hepatic growth, regeneration, tissue differentiation and neoplasia. Converging studies from our lab and others have identified HGF and matrix as key parameters in all these processes. Based on previous work, we have identified different roles and sources for HGF for the first 3 hours after partial hepatectomy (PHx), primarily from pre-existing matrix stores, and following 3 hours after PHx, primarily from newly synthesized HGF. Animal (rat and mouse) models, including conditional homozygous deletion of hepatic HGF gene, are to be employed to study the functions of HGF in liver regeneration. The same models will also be employed to understand the role of hepatic HGF during development of hepatic neoplasia. New HGF at 3 hours post PHx is synthesized not only in liver but also in remote sites. Since we found that norepinephrine stimulates synthesis of new HGF and also rises in the plasma after PHx, will pursue studies to explore the role of norepinephrine as the messenger for HGF synthesis throughout the body after PHx. In studies from the previous period we found that beta-catenin is subjected to tyrosine phosphorylation by cMet. We also now have evidence that beta-catenin is a key regulator of the early stages after PHx and it is subjected to tyrosine phosphorylation by cMet. Studies are proposed to understand the interaction between cMet and beta-catenin, including transgenic mice in which betacatenin is expressed under the albumin promoter. Since beta-catenin mutations are important in liver cancer in humans, the proposed studies will provide information on the function of beta-catenin and its interaction with cMet as regulators of hepatic neoplasia. We have designed organoid cultures in which HGF, EGF and corticosteroids interact in a complex medium (HGM) to allow growth of hepatocytes and nonparenchymal cells, so that they form reproducible and recognizable structures of hepatic histology in a completely defined environment. We have found that corticosteroids and HGF are essential for hepatocyte maturation. HGF and EGF are essential for formation of the complex connective tissue and the fully mature biliary epithelium seen in these cultures. This system allows development biology studies impossible in mouse genetic systems. Proposed studies aim to use this "in vitro embryology" system and provide
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answers on the role of HGF and matrix in hepatic tissue development and differentiation. Finally, we have succeeded in isolating relatively pure material on a key transcription factor (HNFx, for the purposes of the grant) that appears to regulate matrix- and HGF-induced hepatocyte differentiation in culture. Preliminary studies suggest that HNFx is related or identical to Ear2 transcription factor. Studies are described to determine the nature of HNFx and its regulation by growth factors and matrix during hepatocyte differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOMEOSTATIC CONTROL OF AMNIOTIC FLUID VOLUME Principal Investigator & Institution: Davis, Lowell E.; Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Adapted from the Investigator's Abstract) Experiments will be performed on fetal sheep of known gestational ages. Indwelling fetal catheters, flow sensors and amniotic and allantoic fluid catheters will be placed during sterile surgeries under general anesthesia. Hypotheses to be tested include: (l) Urine production, although variable, detracts from, rather than contributes to the control of amniotic fluid volume. (2) Neither lung fluid production, nor drinking of amniotic fluid are necessary for an adequate homeostatic response to abnormal production of amniotic fluid. (3) Fetal swallowing may contribute to amniotic fluid volume regulation even if not necessary in sheep. (4) Reabsorption of amniotic fluid is largely insensitive to electrolyte load. (5) Neither the crystalloid osmotic gradient nor the oncotic gradient between amniotic fluid and fetal plasma are involved in volume regulation. (6) The quantity that is being regulated is amniotic fluid volume, rather than intrauterine volume. (7) The absorptive mechanism permits passage of large quantities of macromolecules, such as plasma albumin, even in the absence of drinking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN ALBUMIN THERAPY OF ACUTE ISCHEMIC STROKE Principal Investigator & Institution: Ginsberg, Myron D.; Professor; Neurology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: In this revised NINDS Pilot Clinical Trial Grant for Neurological Disease, we propose to conduct a phase I investigation of intravenous human serum albumin therapy (HSAlb) for the treatment of acute ischemic stroke. The study is structured as an open-label, non-randomized dose-finding trial that will be conducted at two clinical sites - the University of Miami/Jackson Memorial Hospital and the University of Calgary/Foothills Medical Centre, Canada. Both sites are major University-affiliated teaching hospitals with active Stroke Services and state-of-the-art facilities. The Department of Biometry and Epidemiology at the Medical University of South Carolina, Charleston, will provide data management and statistical analysis. The study's primary objective is to employ a multiple-tier dose-escalation design to discern the safely tolerated maximum dose and administration of intravenous HSAlb in patients with acute ischemic cerebral infarction of 8 hours' duration or less; and to implement standardized procedures for monitoring cardiovascular function and assessing neurological outcome. Our secondary objective is to evaluate neurological and functional outcome at 1 and 3 months after hospital discharge in order to obtain pilot experience for future randomized, multicenter phase II-III trials of this agent. Two
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patient subgroups will be separately and independently studied: those admitted with 3 h who also receive tissue plasminogen activator therapy, and those not receiving tPA. The study's hypothesis is that patients with acute ischemic stroke will tolerate moderate doses of HSAlb without suffering cardiovascular complications or other adverse events. Eligibility criteria include entry within 8 hours; initial NIH Stroke Scale of 6 or greater; and age =greater than 18 years. Major exclusion criteria include congestive heart failure, reduced cardiac ejection fraction by echocardiography, intracranial hemorrhage, severe hypertension, and serious systemic disease. In extensive preclinical studies, we have documented that human albumin therapy confers consistent, marked neuroprotection in animal models of both focal and global brain ischemia as well as in acute brain trauma. We have shown that the therapeutic window for neuroprotection with moderate- dose albumin (1.25 g/kg) extends to four hours after onset of MCA occlusion, and that this albumin dose, when given 2 hours after stroke onset, reduces infarct size even in permanent MCA occlusion. This proposed clinical trial is unique in permitting the opportunity to study this highly efficacious agent at a dose and administration that closely resemble the experimental settings in which its efficacy has already been proven. In our view, the multiple unique physiochemical properties of the albumin molecule are integral to its neuroprotective effect and render it uniquely suited as a therapeutic agent to combat ischemic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
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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: INVESTIGATION OF GLUTARIC ACIDEMIA TYPE I. Principal Investigator & Institution: Koeller, David M.; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Glutaric acidemia type I (GA-I) is an inherited disorder of amino acid metabolism, which in its usual form, causes a progressive extrapyramidal movement disorder and death during the first decade of life. We have recently generated a mouse model of GA-I via gene targeting in embryonic stem cells. The affected mice demonstrate many of the phenotypic features seen in GA-I patients. The goal of this proposal is to use this animal model to answer a fundamental question regarding the pathophysiology of GA-I. Specifically, is the neurologic damage the result of circulating levels of toxic metabolites, or due to the lack of glutaryl CoAdehydrogenase (GCDH) activity within individual neurons (i.e. is it a cell autonomous phenotype). The specific aim of this proposal is to test the hypothesis that expression of the GCDH cDNA in the liver of Gcdh 1" mice will normalize the circulating levels of toxic metabolites (glutaric and 3-OH glutaric acids), and prevent the development of the myelinopathy and motor deficits seen in these animals. The approach we will use is to express the Gcdh cDNA in the liver of Gcdh / animals using the albumin promoter. Current therapy of GA-I consists primarily of a protein-restricted diet, which is based on the assumption that minimizing the levels of glutaric and 3-OH glutaric acids is beneficial. The experiments in this proposal will directly test that assumption. If our hypothesis is correct, the subsequent development of therapies such as liver directed gene therapy and liver stem cell therapy could then begin. Alternatively, if it is determined that normalization of metabolite levels is insufficient to prevent neuropathology in GA-I, alternative approaches to therapy need to be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPID AND PROTEIN EFFECTS ON MONOLAYER STABILITY Principal Investigator & Institution: Zasadzinski, Joseph A.; Professor; Chemical Engineering; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 31-DEC-2004 Summary: Developing new surfactant substitutes requires (1) understanding the roles of the lipids and proteins in native lung surfactant; (2) developing easy to synthesize analogs of the native surfactant proteins; (3) optimizing lipid composition for low surface tension and rapid respreading and adsorption; (4) understanding surfactant inhibition by serum proteins and optimizing surfactant composition to minimize this inhibition. We will use modern biophysical techniques including Langmuir isotherms, fluorescence and Brewster angle optical microscopy, atomic force microscopy, viscometry, and x-ray diffraction to determine the phase behavior and morphology of lung surfactants. Specifically: (1) SP-B eliminates squeeze-out of unsaturated lipids and makes monolayer collapse more reversible. SP-C is more efficient at eliminating squeeze-out, and is less efficient at altering collapse. Is there an optimal ratio of SP-B to
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SP-C, or are the proteins interchangable? (2) Can we make a better SP-B and/or SP-C? Based on the known amino acid sequences of SP-B and SP-C, we will synthesize a family of homodimer peptides that mimic the characteristics of SP-B and SP-C. (3) Is there an optimal solid phase fraction in surfactant monolayers? Adding palmitic acid (PA) to DPPC influences the fluid to solid phase transitions and helps lower the surface tension. We plan to determine the composition of the solid phase in model surfactants and Survanta. (4) What leads to surfactant inhibition by serum proteins? Blood, plasma and serum proteins, lysolipids, and meconium may compete for interfacial area or might solubilize or degrade constituents of surfactant, thereby impairing monolayer function. We propose to investigate the interaction of model lung surfactant mixtures with human serum albumin to determine the molecular mechanisms of surfactant inhibition. (S) Can we relate monolayer viscosity to monolayer morphology and composition? We have built a magnetic needle viscometer to carry out systematic studies of LS monolayer shear viscoelasticity as a function of: i) protein content; ii) phase state of the monolayer. Concurrently, an existing double-barrier Langmuir trough will be adapted to do dilational viscoelasticity under the same conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MACROPHAGE TARGETED PHOTODYNAMIC THERAPY Principal Investigator & Institution: Hamblin, Michael R.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Photodynamic therapy (PDT) may be improved by enhancing the delivery of photosensitizers (PS) to selected lesions using targeted macromolecular conjugates. Recently it has become accepted that tumor-associated macrophages (TAMs) assist the tumor to grow and spread by several distinct mechanisms (paracrine growth factors, increased angiogenesis, and matrix-degrading enzymes) and they have been proposed to be a valid target for cancer therapy. This revised proposal investigates a new approach to killing TAMs by targeted delivery of modified albumin-chlorin (e6) conjugates that are recognized by the scavenger receptors present on TAMs, together with tumor-confined illumination. We have shown that this approach allows very specific photodestruction of mouse macrophages in vitro and leads to substantial inhibition of tumor growth in vivo in both macrophage and nonmacrophage tumors. This proposal will test the hypothesis that the combination of macrophage selectivity and directed illumination will kill TAMs without harming other distant macrophage populations, and hence produce beneficial tumor responses including growth delay, decreased angiogenesis and metastasis, increased survival, and development of tumor immunity. The interaction of the conjugates with macrophages is likely to depend on their cellular activation state and this will be investigated with gene expression arrays and quantitation of scavenger-receptor expression by RT-PCR. J774 cells form highly aggressive and metastatic s.c. tumors in BALB/c mice and the biodistribution and PDT response of these conjugates will be compared to free PS. Immunohistochemistry will allow microvessel density, macrophage content, and proliferative index to be determined in frozen sections from treated tumors. The PDT responses of a pair of s.c. mouse tumors differing in macrophage content and immunogenicity (EMT-6 and RIF- 1) will be determined with quantitative comparison of targeted and non-targeted PDT at roughly equal effective doses. The enhancement of PDT by an adjuvant (OK432) designed to increase the degree of tumor infiltration by TAMs and to increase their activation state will be explored. It is proposed that a PDT response which is inflammatory will encourage the induction of a specific anti-tumor
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immune response, which will be explored by rechallenging cured animals with the same and unrelated cell lines, and measurement of effector cell functions (cytotoxic T lymphocyte, natural killer cell and macrophage) from spleens and draining lymph nodes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPAIR
MAGNETIC
NANOPARTICLE-FACILITATED
SPINAL
CORD
Principal Investigator & Institution: Halpern, Alan A.; Orthopedic Development, Inc. 1400 Low Rd Kalamazoo, Mi 49008 Timing: Fiscal Year 2003; Project Start 19-FEB-2003; Project End 31-JAN-2004 Summary: (provided by applicant): An injured mammalian spinal cord will not spontaneously repair itself. The goal of this project is the development of a system for axonal growth and restoration of spinal cord function, in which polymer and anti-Li magnetic nanoparticles are attached to the growth cones of traumatized axons, which are then induced to grow distally along the magnetic flux lines from an external magnetic field. This would represent a unique and patented method that would involve (1) a new surgical technique, (2) an injectable device, and (3) a device to create a precise magnetic field. It has been shown that tension applied to CNS neurons does indeed stimulate directional growth. In previous studies, ODI has shown that BSA-coated particles are phagocytosed by CNS neurons and that the cells can be directed to grow magnetically. This Phase I study will seek to demonstrate the optimal particle characteristics to maximize uptake, using an organotypic technique and in vivo administration to an acutely traumatized rat spinal cord. A further experiment will seek to determine the volume of particles that must be incorporated to enable the axon/particle complex to be directed through a viscous column with a magnetic field gradient of 7000 Gauss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS NEUROTOXICITY
AND
PREVENTION
OF
HEMOGLOBIN
Principal Investigator & Institution: Panter, S Scott.; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-JUL-2004 Summary: (Adapted from investigator's abstract) The central hypothesis of this proposal is that hemoglobin is cytotoxic and will significantly worsen cellular injury produced by the original ischemic episode. This contribution of hemoglobin to neurological injury can be reduced by pretreatment with antioxidants, chelators, the hemoglobin binding protein haptoglobin, or agents that will plug the barrier, blocking the entry of hemoglobin. This proposal will focus on a rat model of focal ischemia and reperfusion that has been demonstrated to disrupt the blood-brain barrier. To attempt to model the clinical situation, stroma-free or purified human hemoglobin will be infused into the vasculature of rats at the start of reperfusion following focal ischemia. This procedure results in the direct deposition of hemoglobin into the ischemic area of the brain through the disrupted BBB. Increasing doses of hemoglobin will be administered to assess behavioral impairment and survivability. At different time intervals following stroke, the brains will be evaluated for infarct size, cerebral edema, and the degree of disruption of the blood-brain barrier. Neuronal degeneration will be assessed by conventional histology and fluorescence microscopy using fluoro-jade. Finally, animals will be
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pretreated with an antioxidant (polynitroxyl-albumin), an iron chelator (a starch deferoxamine conjugate), the normal hemoglobin-binding protein haptoglobin, or a subfraction of pentastarch that has been shown to physically plug the holes of a disrupted blood-brain barrier. These studies will delineate a hemoglobin-dependent contribution to neural injury following opening of the blood-brain barrier and will test several therapeutic candidates that could be used in the clinical setting of CABG surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF CAPILLARY PERMEABILITY Principal Investigator & Institution: Schnitzer, Jan E.; Scientific Director; Sidney Kimmel Cancer Center San Diego, Ca 921211181 Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-MAR-2005 Summary: (Adapted from the application): Blood vessels are lined with a thin layer of specialized cells called endothelium that forms a critical barrier controlling the exchange of circulating blood molecules, nutrients, cells and even drugs from the blood to the internal compartments and cells of the tissue. This exchange defines the molecular permeability of small blood vessels called microvessels or capillaries and is critical for the normal growth, maintenance and survival of all tissues of the body. Abnormal exchange contributes to organ dysfunction, tissue cell death, and the pathogenesis of many cardiovascular diseases such as atherosclerosis and complications of diabetes. The broad focus of this project is to define the molecular and cellular basis of the barriers and pathways that mediate capillary permeability. The ability of the endothelium to act both as a restrictive barrier to transvascular exchange and as a specific receptormediated translocator of molecules is dependent on cell surface population of distinct vesicles called caveolae which may play an important role in the transport of select macromolecules into and across the endothelial cell barrier. The molecular structure and function of caveolae will be investigated by using novel technologies and transport assays developed in the lab. Because albumin is the major protein in blood and acts as a carrier for many important nutrients, we will examine its interactions with the endothelium. Albumin can increase the restrictiveness of the endothelial cell barrier while conversely facilitating the transendothelial transport of select molecules such as fatty acids and even drugs. The mechanisms mediating these effects are uncertain. The investigator's work discovered that albumin interacts with endothelium and traverses it by binding to a specific receptor called albondin (gp60), which is concentrated in caveolae that can bud from the cell surface to form free transport vesicles. Specific albumin binding domains in albondin will be determined. Small molecules will be created to inhibit albumin binding and transport. The mechanisms by which caveolae transport their molecular cargo via the distinct steps of budding, docking and fusion will be examined at the molecular level. Because mutations in specific caveolar proteins inhibit transport, the investigators will study how these proteins function in caveolar transport. Their quest for basic knowledge at the molecular level about the function of caveolae and vascular endothelium in transport has elucidated novel targeting strategies that are potentially useful in achieving tissue-specific drug and gene delivery for the treatment of many diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR CRYSTALLIZATION
MODULATION
OF
CALCIUM
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OXALATE
Principal Investigator & Institution: De Yoreo, James J.; Senior Scientist; Materials Science & Technology; University of Calif-Lawrnc Lvrmr Nat Lab Lawrence Livermore National Lab Livermore, Ca 945509234 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Urinary tract stone disease (urolithiasis) is a common clinical disorder that frequently leads to hospitalization. The objective of this proposal is to advance the understanding of the pathogenesis of urolithiasis by determining the physical mechanisms through which important inhibitors that include small urinary molecules, such as magnesium and citrate that are currently used in the treatment of urinary tract stone disease and urinary macromolecules, such as osteopontin control the nucleation, growth, aggregation, and phase transformations of calcium oxalate (CaOx) precipitates. This objective will be accomplished by investigations focusing on 1). the mechanisms of modulation of CaOx nucleation and growth by small urinary molecules and urinary macromolecules, 2). the mechanisms by which urinary modulators affect the sequence of events during phase transformations of CaOx crystals and 3). the surface interactions and events underlying urinary protein modulation of CaOx aggregation. The proposed research will use in situ atomic force microscopy to follow the evolution of CaOx crystal surfaces and quantify the impact of growth modulators on the thermodynamic and kinetic factors controlling the dynamics of atomic steps on those surfaces. This work will lead to new insights that integrates an understanding of the specific stereochemical interactions on the crystal surface with the quantitative impact on kinetics and morphology. The atomic force microscopy measurements will be correlated with concurrently performed constant composition measurements of growth kinetics and contact angle measurements of interfacial energies. The knowledge derived from our studies will assist in the design of inhibitory molecules that are potentially useful in therapy of stone disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NATURAL HISTORY OF MICROALBUMINURIA IN TYPE 1 DIABETES Principal Investigator & Institution: Krolewski, Andrzej S.; Associate Professor; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 01-FEB-1990; Project End 31-MAR-2009 Summary: (provided by applicant): End stage renal disease (ESRD) is the major health problem for patients with type 1 diabetes (T1DM), afflicting about 25%. Unfortunately, during the last 20 years the risk of ESRD due to T1DM in the U.S. population has not declined despite widespread use of reno-protective drugs. Clearly, new knowledge of the causes of renal function decline in T1DM is urgently needed in order to design more effective interventions. From our recent findings it appears that only 30% of patients with T1DM and microalbuminuria (MA) develop clinically significant renal function decline, whereas the rest have stable renal function, as do those without MA. The most interesting aspect of this finding is that the decline for this subset of patients begins with the onset of MA, when renal function is at or above a normal level (average GFR 150 ml/min) and is unrelated to urinary albumin excretion rate within MA or ACE inhibitor treatment. Once initiated, it appears that renal function decline progresses unabated. The main goal of this application is to identify determinants of this early renal function decline and to consider their potential as diagnostic predictors of renal function loss in
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individuals with T1DM and MA while their renal function is still normal. This application aims to examine the following in the 2nd Joslin Study: 1) The frequency of early renal function decline in 954 patients with T1DM and MA already recruited into the 2nd Joslin Study and who will be followed at least for 4 years; 2) Independent and joint effects of various kidney risk factors on early renal function decline, including a) Intensity of glomerular filtration barrier damage as reflected in urinary excretion of albumin and IgG, b) Intensity of urinary excretion of pro-inflammatory cytokines (TNFalpha, IL-1beta, INF-gamma, and IL-6), c)Intensity of urinary excretion of chemokines (IL-8, MCP-1, IP-10, and RANTES) considered causes or markers of renal tubulointerstitial damage; 3) Independent and joint effects of systemic risk factors such as HbA1c, total serum cholesterol, serum triglycerides, cigarette smoking, blood pressure and ACE inhibitor treatment on the occurrence of early renal function decline; 4) Genetic determinants of early renal function decline. This will include the following candidate genes: genes previously shown to contribute to susceptibility to ESRD (eNOS, and ENPP1/PC-1), and genes encoding for selected chemokines (IL-8, MCP-1, IP-10, and RANTES) and their receptors (IL8RA, IL8RB, CCR2, CXCR3 and CCR5). If our research is successful, individuals at high risk of renal function loss can be identified and targeted for intervention 5-10 years earlier than currently achievable, possibly with protocols aimed at new therapeutic targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OBESITY AND NONALCOHOLIC FATTY LIVER DISEASE Principal Investigator & Institution: Klein, Samuel; Professor of Medicine and Director; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2004; Project Start 01-DEC-1986; Project End 31-MAR-2009 Summary: (provided by applicant): Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of liver diseases characterized histologically as steatosis, steatohepatitis, fibrosis and cirrhosis. NAFLD is a major health problem in the U.S. because of its high prevalence and causal relationship with serious liver abnormalities. However, the mechanism(s) responsible for developing NAFLD in obese persons and the effects of NAFLD itself on hepatic metabolic function are not known. This gap in knowledge has made it difficult to identify effective therapy. Although weight loss is generally recommended for obese patients with NAFLD, the available data suggest that rapid and marked weight loss increases inflammation, and even liver failure. The primary goal of this proposal is to provide a better understanding of: 1) the pathogenesis and pathophysiology of NAFLD in obese persons, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. We will test the following hypotheses: 1) obesity causes hepatic fat accumulation, because of excessive fatty acid release from adipose tissue and increased FFA availability, 2) increased hepatic fat content causes insulin-resistant glucose production by the liver and altered hepatic lipoprotein and protein synthesis, 3) increased hepatic fat content causes increases lipid peroxidation and hepatic oxidative stress, hepatic inflammation, necrosis and fibrosis, and 4) marked weight loss improves the histological and metabolic features of NAFLD once patients are weight stable. Two study protocols will be performed. In Protocol 1, 30 subjects with class I obesity (BMI 3034.9 kg/m 2) and NAFLD will be randomized to 6 weeks of a low-carbohydrate, highfat diet (to increase lipolysis and plasma FFA availability), niaspan therapy (to decrease lipolysis and plasma FFA availability), or observation (control). An additional 10 obese subjects with normal hepatic lipid content will also be treated with a low-carbohydrate, high-fat diet to determine whether excess FFA availability also increases hepatic fat in
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persons with normal liver. In Protocol 2, subjects with class II and III obesity (BMI 35-50 kg/m 2) will undergo gastric bypass surgery. The following metabolic evaluations will be performed before and after the interventions: 1) assessment of basal glucose and fatty acid kinetics, 2) assessment of liver, adipose tissue, muscle and insulin sensitivity during a hyperinsulinemic-euglycemic clamp procedure, 3) hepatic lipoprotein metabolism (VLDL-TG and VLDL-apolipoprotein B secretion), 4) hepatic protein (albumin, and fibrinogen) synthesis, 4) assessment of hepatic fat content by magnetic resonance spectroscopy (in Protocol 1 subjects only), and 5) liver lipid peroxidation and fibrogenesis by using immunohistochemistry. The results from these studies will lay the groundwork for the development of novel therapeutic interventions for NAFLD in obese patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONCOTIC PRESSURE AND EXTRAVASCULAR LUNG WATER IN ARDS Principal Investigator & Institution: Martin, Gregory S.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Applicant's Abstract This proposal is part of a career development plan integrating didactics in the form of a Master's Degree in Clinical Investigation with direct, mentored experience in the design and conduct of randomized clinical trials. Expertise in these areas will provide the necessary components for a successful career in patient-oriented critical care research. The Center for Lung Research at Vanderbilt University has focused substantial efforts toward the understanding of fluid and solute exchange in the injured lung, both in the pre-clinical arena and in prospective, randomized clinical trials. The mentors and consulting faculty in this environment are well recognized, established senior investigators in critical care research with vast preclinical and clinical experience. ARDS is defined by acute impairment of oxygenation and radiographic infiltrates compatible with pulmonary edema without increased hydrostatic pressures. It affects approximately 15,0000 people per year in the United States, with mortality approaching 50% and a financial burden estimated to exceed $5 billion. Fluid overload, weight gain, and hyperproteinemia are associated with increased mortality in patients with ARDS. Reduced oncotic pressure gradients related to hypoproteinemia may contribute to generation and maintenance of pulmonary edema in this condition. Previous trials have demonstrated clinical benefits associated with albumin and diuretic therapy in patients with ARDS, through the mechanisms by which these improvements occur is unclear. It is hypothesized that these benefits occur through increases in the oncotic pressure gradient and reductions in extravascular lung water, through the exact mechanism is unknown. The purpose of this project is to elucidate the pulmonary and hemodynamic effects of colloid and diuretic therapy in patients with ARDS using recently developed technology, which permits simple and accurate measurement of systemic hemodynamics and extravascular lung water in critically ill patients. This investigational proposes a critical trial randomizing hypoproteinemic ARDS patients to albumin and furosemide or dual placebo with targeted goals of diuresis and weight loss. Therapeutic effects on respiratory function, extravascular lung water, oncotic pressure, alveolar fluid clearance, and systemic hemodynamics will be characterized. This trial could advance our understanding of factors affecting fluid balance in patients with ARDS and has the potential to change clinical practice standards. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OVARY SELECTIVE GENES: CRITICAL OVARIAN REGULATORS Principal Investigator & Institution: Adashi, Eli Y.; Presidential Professor of Obstetrics And; Obstetrics-Gynecology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 07-JUN-1999; Project End 31-MAY-2004 Summary: Ovary-selective genes constitute a subset of genes characterized by preferential or exclusive ovarian expression. The critical importance of the ovaryselective genes c-mos, ZP-3, GDF-9, and alpha-inhibin to murine ovarian function was established with null mutants which displayed markedly aberrant ovarian phenotypes and consequent infertility. A loss of function mutation in women established the critical role of the FSH receptor in ovarian function. These observations underlie the hypothesis that ovary- selective genes constitute critical molecular determinants of ovarian function. Thus far, the isolation, identification, and characterization of such ovaryselective genes has proceeded on a case-by-case basis. In this application, we propose a systematic approach. In this context, we report preliminary studies on the use of Suppression Subtractive Hybridization to construct an ovary-selective cDNA library. Ongoing screening of 327 clones has yielded 35 putative novel cDNAs lacking homology to any sequence entry deposited in publicly-accessible databases. We also report preliminary studies on the utility of conditional Cre/LoxP technology with an eye to effect ovary-selective gene deletion. Using the igf-1 gene as a testing paradigm, we document its successful "floxing" and selective deletion in the liver following crossing with a Cre transgenic driven by the albumin promoter. Preliminary studies are reported as to the generation of a Cre transgenic driven by the alpha-inhibin promoter in the hope of effecting granulosa cell-selective deletion of any "floxed" gene of interest. To complete the identification and begin the characterization of novel ovary- selective cDNAs, this proposal outlines a series of complementary in vitro and in vivo experiments. Specifically, we propose to: I) complete the identification of ovary-selective cDNAs using high-throughput robotics and microarrayed DNA chip technology, II) isolate and sequence the full-length of novel ovary-selective cDNAs, III) study the hormonal dependence, (cycle) phase-specific expression, and cellular localization of novel ovary-selective genes and IV) assess the functional role of three novel ovaryselective genes by effecting conditional ovarian gene deletion. Insight derived from this investigation may contribute to novel strategies for the promotion of fertility or its control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AMYLOIDOSIS
PATHOGENESIS
OF
HEREDITARY
TRANSTHYRETIN
Principal Investigator & Institution: Benson, Merrill D.; Professor; Medical and Molecular Genetics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-MAR-2004 Summary: (from abstract): The overall objective of this proposal is to define the pathophysiology of the autosomal dominant transthyretin amyloidoses. These diseases, while considered rare, are actually being recognized in increased numbers of kindreds throughout the world and especially in the United States. Transthyretin amyloidosis is usually associated with peripheral neuropathy, nephropathy, and cardiomyopathy which present as late-onset (adult) disease with high degrees of morbidity and mortality. To date at least 72 variants of transthyretin (TTR) have been found to be associated with systemic amyloidosis which is inherited as an autosomal dominant
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disease. Of particular concern is the fact that: 1) it has recently been shown that there are elderly individuals who develop transthyretin amyloid cardiomyopathy (senile cardiac amyloldosis) in the absence of any detectible mutation in transthyretin; and, 2) there is a high prevalence of one particular transthyretin mutation (isoleucine 122) in the American Black population and this is manifest as amyloid cardiomyopathy. These two findings suggest that, as the population ages, amyloid heart disease will become of greater significance to the American population. Previous studies have centered on determining structural changes of transthyretin which are related to amyloid formation. Structures of amyloid forming variants methionine 30, serine 84, alanine 60, arginine 10, tyrosine 77 have been compared to structures of non amyloid forming threonine 109, serine 6, methionine 119 and normal transthyretin. No common structural change has been found to explain initiation of the fibril forming process but preliminary data suggest that solvent accessability to variant transthyretin dimers may allow a proteolysis event which could lead to the initiation of fibril formation. Metabolic studies using radiolabelled variant and normal transthyretins have suggested increased plasma clearance of variant proteins. The Specific Aims will test the hypothesis that single amino acid substitutions in transthyretin result in changes in tertiary structure of the transthyretin molecule which allow alterations in metabolism of the variant molecule and its associated normal monomers to lead to amyloid formation. Transthyretin proteins isolated from tissues of patients with amyloidosis will be studied to characterize proteolytic peptides and determine if partial proteolysis with generation of carboxyl terminal peptides is a factor in amyloid fibril formation. Fibril forming potential of these fragments will be tested by producing recombinant protein of residues 49 - 127 and testing fibril formation with and without full-length transthyretin in vitro. A new Specific Aim will test the hypothesis that the ratio of the various tetrameric forms of transthyretin affects the propensity to form amyloid fibrils. To accomplish this aim a dual expression system in baculovirus coexpressing normal TTR and variant TIR has been developed. These studies are directed at developing methods to prevent amyloid formation from variant TTR proteins and, thereby providing therapeutic options for a disease which at the present time has no specific therapy other than liver transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEPTIDES AND ALCOHOL INTERACT AT THE BLOOD-BRAIN BARRIER Principal Investigator & Institution: Kastin, Abba J.; Editor in Chief; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAR-2006 Summary: The blood-brain barrier (BBB) is no longer considered a static wall restricting circulating peptides from the brain. Many peptides have been shown to penetrate the BBB, some by diffusion and some by selective transport mechanisms. The interaction of alcohol at the BBB with certain peptides that can affect alcohol ingestion would provide a novel site of regulation. It is proposed that alcohol increases the entry of angiotensin II (AT), cholecystokinin-8 (CCK), leptin, and tumor necrosis factor-alpha (TNF) into brain from the circulation, thus inhibiting alcohol ingestion. The effects of alcohol ingestion on the rate and saturation (self-inhibition) of entry of peripherally injected AT, CCK, leptin, and TNF into the brains of mice will be determined by multiple-time regression analysis and also blood-free perfusion. HPLC will determine that the iv injected substance reaches the brain intact, capillary depletion with washout will show that it is not bound to the capillary endothelium or loosely associated with vascular elements, and
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measurement of efflux from brain will rule out possible confounding effects on influx. Simultaneous injection of albumin will control for leakage of blood and non-specific entry. Cross-inhibition, particularly of TNF on leptin transport, will determine whether TNF affects leptin at the BBB as it does at the adipocyte. Alcohol-induced transport of these four substances into brain is probably at least partially mediated by transporters different from their receptors. After the isolation and identification of these transport proteins, the effects of ethanol on their distribution in brain will be quantified by autoradiographic image analysis. These sensitive procedures will show that the BBB serves as a dynamic site for the interaction of alcohol and peptides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PH CONTROL OF PROTEIN SYNTHESIS Principal Investigator & Institution: Garlick, Peter J.; Professor and Director of Research; Surgery; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Patients with renal failure, diabetic ketosis, severe trauma or sepsis often become acidotic. Moreover, they are also susceptible to body protein wasting. Experimental acidosis has been shown to result in negative nitrogen balance, and body protein loss in acidotic patients can be alleviated by normalization of pH. Previous work has concentrated on the effects of pH on protein degradation and no systematic studies have been performed on pH and protein synthesis. However, measurements in animals and human volunteers have shown that both metabolic and respiratory acidosis are associated with depressed rates of synthesis of skeletal muscle protein and serum albumin. The purpose of the present proposal is therefore to characterize the relationship between protein synthesis rates in tissues, especially muscle and liver, of rats and humans in relation to changes in intra- and extracellular pH, to confirm the hypotheses: (i) that changes in blood pH, both by metabolic and respiratory means, modify rates of tissue protein synthesis and gene expression and contribute to the protein wasting of patients with acidosis, and (ii) that these effects of pH operate directly via the intracellular pH and do not involve extracellular mediators such as hormones. The studies will employ measurements of rates of protein synthesis in tissues of rats and human volunteers to characterize the responses to changes in intra- and extracellular pH induced by metabolic and respiratory means and to confirm that these effects are rapid, operate over the full range of pH from acidosis to alkalosis and are independent of oxygen supply. In the animals, the responses of gene expression in the liver will be investigated by determining the levels of mRNA for 3 liver proteins. In particular, the treatments studied will produce different changes in the infra- and extracellular pH. Measurements of intracellular pH will be made by nuclear magnetic resonance, to confirm the hypothesis that changes in protein synthesis are determined by the intracellular rather than extracellular pH. A separate set of studies will be performed in isolated tissues and cells, to determine whether responses to changes in pH are direct or act through circulating hormones. The cellular and molecular mechanisms through peptide chain initiation and initiation factors eIF-2 and eIF-4 will also be identified. Finally, the effect of changes in pH on tissue protein synthesis will be measured in human volunteers and hemodialysis patients, to identify the role of pH control of protein synthesis in health and in protein wasting conditions with abnormalities of pH control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--MICROCIRCULATORY NEPHROPATHY
RESPONSE
IN
55
DIABETIC
Principal Investigator & Institution: Pergola, Pablo E.; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Diabetic nephropathy is the leading cause of end-stage renal disease in the United States. Microalbuminuria (albumin excretion rate between 30-300 mg/day) is the earliest clinically recognizable stage of the disease. Currently, no reliable clinical markers are available that allow us to identify diabetic patients at risk to develop nephropathy. The renin angiotensin system (RAS) is implicated in its pathogenesis. Skin manifestations of diabetic microangiopathy are similar to those observed in the kidney. Hypothesis: Diabetic patients at risk of developing nephropathy can be identified prior to the development of microalbuminuria by their pattern of microcirculatory responses to activation and blockade of the renin-angiotensin system. We propose to identify differences in the skin blood flow responses to pharmacological manipulations of the cuatneous renin-angiotensin system between healthy subjects, patients with diabetes without microalbuminuria, and patients with diabetes with micro or macroalbuminuria. Methods: Drug delivery will be achieved by intradermal microdialysis combined with local skin blood flow measurements by laser-Doppler flowmetry. Healthy volunteers and subjects with diabetes (males and females) will be included in this study. Patients with diabetes and with normal urine albumin excretion rates or with microalbuminuria will have normal blood pressure (<130/80) and normal renal function (serum creatinine < 1.2 for women, <1.3 for men). We have already characterized the skin RAS in normal volunteers. This will allow us to compare the responses to manipulations of the RAS between healthy subjects and patients with diabetes with and without nephropathy. We anticipate finding changes in the skin microcirculation mediated by the RAS that precede the appearance of microalbuminuria that may allow us to predict which diabetic patients are at risk to develop nephropathy. Long-term studies will include the correlation of these phenotypic findings with known mutations in the angiotensin II type 1 receptor and angiotensin converting enzyme genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PKA IN REDUCTION OF ENDOTHELIAL PERMEABILITY Principal Investigator & Institution: Lum, Hazel; Associate Professor; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Evidence indicates that cAMP, and thus cAMPdependent protein kinase (PKA), is highly effective in prevention of increased vascular endothelial permeability induced by inflammatory mediators. Our preliminary findings indicate that regulation of permeability occurred at the level of cadherin/catenin linkage to actin and that cAMP inhibited RhoA activation, an important molecule in actin remodeling and barrier dysfunction. We showed that isoforms of PKI, the PKA inhibitor protein, are widely expressed by endothelial cells, suggesting an added level in permeability regulation and underscores the role of PKA. We propose to test the hypothesis that PKA prevents development of mediator-induced barrier dysfunction through stabilizing the linkage between the VE-cadherin/catenin protein complex with actin through signaling Rho GTPases. Since cAMP has PKA-independent actions, Aim 1 will first evaluate PKA-dependency of the cAMP signal in prevention of increases in permeability. PKA will be inhibited by use of adenoviruses containing PKI or
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pharmacologically and the permeability measured by transendothelial resistance and transvascular FITC-albumin leak in the cremaster muscle. Aim 2 will investigate whether PKA stabilizes associations of VE-cadherin and catenins to actin using methods of detergent fractionation, co-precipitation, and immunofluorescent localization. Aim 3 will investigate mechanisms by which PKA signal regulation of Rho, Rac, and Cdc42. The studies will determine whether PKA coordinates signaling intermediates (i.e., protein phosphatase 2B) to regulate Rho GTPase activation and GTP/GDP cycling. Rho GTPase activity will be assessed by affinity binding of activated proteins with GSTfusion target proteins and by subcellular translocation. Aim 4 will investigate whether Rho GTPases regulate endothelial permeability by regulating the VE-cadherin/catenin linkage to actin. The effects of altered Rho GTPase activity by use of bacterial toxins such as C3 and CNF1 and expression plasmids containing dominant-negative and active mutants of RhoA, Rac1, or Cdc42 will be determined. Aim 5 will test the hypothesis that the level of PKL expression regulates the extent of barrier restrictiveness. PKI expression or function will be altered by use of adenoviruses containing PKIgamma or PKIbeta isoforms to investigate regulation of the cadherin/catenin proteins, Rho GTPase activity, and barrier function assessed by in vitro and in vivo assays of permeability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRIMARY PREVENTION PROGRAM -DATA COORDINATING CENTER Principal Investigator & Institution: Fowler, Sarah E.; Research Professor; Statistics; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 20-AUG-1994; Project End 31-MAY-2003 Summary: (Directly incorporated from the application) The Biostatistics Center of The George Washington University proposes to work in cooperative agreement with the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) to serve as the Data Coordinating Center (DCC) for a proposed multi-center clinical trial of the primary prevention of non-insulin dependent diabetes mellitus (NIDDM). Adiposity and inactivity have been established as critical factors in the etiology of glucose intolerance and are strongly associated with increased risk of glucose intolerance. We propose to determine the safety and efficacy of an intensive lifestyle intervention or prophylactic use of an oral hypoglycemic agent on the incidence of NIDDM among high risk patients (obese, minority, family history of NIDDM, history of gestational diabetes mellitus) in a state of impaired glucose tolerance (IGT). The objective of the one year planning phase is to develop a protocol, operations manual and data collection forms to be implemented in a five year full-scale clinical trial. The trial will require large-scale screening and randomization of 4,000 high risk patients with a diagnosis of IGT over a one year period in 20 clinical centers. Eligible patients will be randomized to "conventional" dietary counseling or one of the comparison groups (intensive lifestyle intervention or an oral hypoglycemic agent). Randomized patients will be followed for a minimum of four years with quarterly follow-up visits. Conversion from a state of IGT to overt NIDDM will be determined by semi-annual 2-hour oral glucose tolerance tests (OGTTs) following a 75 g glucose load confirmed by a central laboratory. Covariates and secondary outcomes include carotid ultrasound imaging, electrocardiograms, serum lipids, albumin excretion rate, adiposity, insulin sensitivity, hemoglobin A1c, and fundus photographs. The specific aims of the DCC are to provide centralized support and biostatistical consultation in the development of the patient management protocols, operations manual, data collection forms and randomization procedures;
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implementation of a data processing system including data quality assessment; interim analysis of protocol performance, patient safety and treatment efficacy; and final analysis for publication of the results in collaboration with the clinical investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROMOTING INTERVENTIONS
ELDER
HEALTH
WITH
NUTRITIONAL
Principal Investigator & Institution: Crogan, Neva L.; Nursing; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): The purpose of this 18-month pilot study is to test the effect of a prevention-focused nutritional intervention for nursing home residents. The individualized Nutrition Rx protocol has the potential to improve residents' overall quality of life, and reduce health care utilization. The protocol is based upon Minimum Data Set that was collected and analyzed during a previous study. Nutrition related data were analyzed to identify predictors of protein-caloric malnutrition in nursing home residents. The significant predictors will be used to identify at risk residents who then will be invited to participate in the pilot, prevention-focused intervention. A twogroup pre-post design will be used in this pilot study. Residents (N=110) from three nursing homes will be invited to participate. One nursing home will be designated for the intervention group, the other two the care as usual group. Intervention group residents will receive the proactive treatment package that is a six component comprehensive assessment with individualized interventions. Both intermediate outcomes (BMI, serum albumin and prealbumin) and long-term outcomes (quality of life, morbidity, and health care utilization) will be measured. Repeated measures ANOVA will be used to compare the mean endpoints for the two groups. Study findings are anticipated to 1) provide preliminary data about the effectiveness of the intervention to prevent malnutrition in at-risk elders; and 2) provide pilot data for largescale intervention studies that will improve the nutritional health of at-risk elders living in nursing homes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PULMONARY INTERSTITIAL MECHANICS Principal Investigator & Institution: Lai-Fook, Stephen J.; Professor; Ctr for Biomedical Engineering; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: The pulmonary interstitium is a pathway that drains microvascular filtrate from the lung. Thus its properties are important to the understanding how normal fluid balance is maintained and the pathogenesis of pulmonary edema. The clearance of interstitial fluid depends on bulk flow caused by differences in hydrostatic pressure and osmotic flow caused by differences in protein concentration. In previous studies, the effects of hydration, protein concentration, fluid viscosity, electric charge, and hyaluronidase on interstitial conductivity were measured. The effects of albumin and hyaluronidase were opposite to those expected from steric exclusion in solutions of albumin and hyaluronan. Recent studies indicated interstitial sieving of albumin and a finite reflection coefficient that increased at low concentrations with normal hydration, in conjunction with free diffusion of albumin. Such a membrane-like property is opposite to the properties of solutions usually assigned to interstitium. A major goal is to describe the interstitium in terms of its membrane properties. The effect of
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hyaluronidase on interstitial sieving of albumin and the effect of hydration on the reduced diffusive response to hyaluronidase will be studied. The sieving behavior measured in interstitial segments during steady state flow will be supported by studies of the longitudinal gradient in albumin concentration during interstitial cuff growth in liquid-inflated.lungs. These studies will measure steric exclusion of albumin in interstitial cuffs of vessels ranging from arterioles to large vessels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REDUCING RENAL TGF-B IN DIABETIC GLOMERULOSCLEROSIS Principal Investigator & Institution: Cohen, Margo P.; Professor and Director; Exocell, Inc. 3508 Market St, Ste 420 Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2003 Summary: (provided by applicant): The objective of this project is to develop for clinical use a novel pharmacologic agent for the prevention/treatment of diabetic glomerulosclerosis. The rationale for this application derives from our work encompassing in vitro and in vivo studies that have elucidated the important role of nonenzymatically glycated albumin in the pathogenesis of diabetic nephropathy, delineated molecular messengers responsible for glycated albumin-induced stimulation of glomerular extracellular matrix production, and demonstrated that reducing the burden of glycated albumin with the small molecule designated 22CPPA attenuates all of the structural and functional changes of diabetic kidney disease in the db/db mouse. 22CPPA inhibits the condensation of glucose with reactive amino groups in albumin and significantly lowers serum concentrations of glycated albumin in hyperglycemic, diabetic animals, resulting in a reduction of the glomerular over-expression of TGFBeta1 and prevention of glomerulosclerosis and renal insufficiency even when hyperglycemia prevails. Based on these findings, we propose that targeting the overexpression of glomerular TGF-Beta1 through inhibiting the excess nonenzymatic glycation of album in diabetes is a viable therapeutic strategy for preventing the progression of diabetic nephropathy and that 22CPPA is a novel clinical candidate for treatment of this morbid complication of diabetes. The Phase I goals of this project are to delineate the dose-response profile of 22CPPA on the therapeutic targets, and to examine its acute lethality/toxicity. During Phase I we will work with a contract manufacturer for manufacture of GMP grade 22CPPA, which will be used for the formal animal toxicology and pharmacokinetics that will be performed in Phase II to support initial exposure of humans to the compound in clinical Phase I (safety) and Phase II (early efficacy) trials that also will be undertaken in the Phase II project. Animal toxicology will be conducted with the same lot of GMP grade 22CPPA that is used in clinical trials arid will be commensurate in duration and dosage with the clinical testing to be performed. The specific Aims of time Phase I project, which will constitute Milestones, are to: 1) Perform dose-response efficacy studies amid determine optimum dosing range for meaningful reduction of glomerular TGF B1 and plasma glycated albumin in diabetic rodents; 2) Conduct in vivo studies of acute toxicity/lethality of 22CPPA; and 3) Begin process development with a contract manufacturer for clinical grade (GMP manufactured) 22CPPA that meets requirements with respect to best yield/minimal side products, and concurrently plan for relevant analytical development amid testing, validation, purity, and stability so as to obtain drug substance that is suitable for formal animal toxicology to support use in human subjects, and for conduct of Phase I arid II clinical trials during the Phase II project. PROPOSED COMMERCIAL APPLICATIONS: This project seeks to develop for clinical use a novel pharmacologic
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agent for the prevention/treatment of diabetic glomerulosclerosis, and is expected to result in commercialization partnering. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATED POLYADENYLATION OF MESSENGER RNA Principal Investigator & Institution: Schoenberg, Daniel R.; Professor; Molecular & Cellular Biochemistry; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-DEC-2004 Summary: (Adapted from the applicant's abstract) This investigator previously showed that Xenopus albumin mRNA isolated from either the cytoplasmic or nuclear fractions has an unusually short and discrete 17 residue poly(A) tail. A similarly short poly(A) tail was subsequently identified on a number of other mRNAs that were posttranscriptionally regulated in a manner similar to the albumin mRNA and demonstrated that the short poly(A) tail was feature of unprocessed nuclear albumin pre-RNA. The short poly(A) tail results from the presence of a poly(A)-limiting element (PLE) in the terminal exon of the albumin gene. A data based search has identified hundreds of genes with PLE like elements and this investigator demonstrated the functionality of the PLE in the gene encoding the HIV-EP2/Schnurri 2, a zinc finger transcription factor that activates transcription of the integrated HIV-1 provirus. The overall results suggest that there are at least two categories of polyadenylated mRNAs; those that exit the nucleus with a 200+ poly(A) tail, and those that exit the nucleus with a discrete, <20 nt poly(A) tail. The overall goal of this proposal is to define the molecular mechanism responsible for regulating poly(A) tail length, and to define the functional consequences of this process on the metabolism and translation of mRNAs with short poly(A) tails. The specific aims of this project therefore seek to 1) identify and characterize the nuclear PLE binding protein (PLE-BP); 2) to determine the functional interactions of the PLE-BP in order to elucidate the mechanisms by which PLE and PLEBP regulate poly(A) tail length; and 3) to determine the functional consequences of limiting poly(A) to less than 20 nucleotides on export of mRNA from the nucleus, on the turnover of both stable and unstable mRNAs, as well as on translation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF DIFFERENTIATION IN HEPATOCYTES IN VITRO Principal Investigator & Institution: Isom, Harriet C.; Distinguished Professor; Microbiology and Immunology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 01-SEP-1978; Project End 31-JAN-2004 Summary: This grant has been continuously funded for more than nineteen years to study REGULATION OF DIFFERENTIATION IN HEPATOCYTES IN VITRO. The applicant has established two in vitro culture systems. (1) A long term culture system for primary hepatocytes in which the cells are maintained in a chemically-defined medium supplemented with dimethylsulfoxide (DMSO), and (2) A series of immortalized hepatocyte cell lines, transformed cell lines and tumor cell lines that retain the ability to express liver-specific functions, some at liver-like levels. During the current funding period, she has utilized both systems to make several important findings. She has demonstrated that hepatocytes in long-term DMSO culture: (1) Maintain the potential not only to undergo DNA synthesis but also to proliferate, (2) Can differentiate into bile duct-like cells, and (3) Can express specific oncogenes and growth factors in a similar pattern to what is observed in regenerating liver, when induced to synthesize
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DNA. Using immortalized hepatocyte cell lines and transformed and tumor cell lines derived from them, the applicant has made several contributions with regard to the effect of transformation on expression of differentiated functions, regulation of albumin and alpha 1 integrin expression, factors that suppress the transformed phenotype in transformed hepatocytes and differential responses of premalignant and malignant cells to TGF-beta. She has also made several important technical advances in gene delivery that will enable her to carry out both gain and loss of function studies in both culture systems. In the current application, the applicant proposes to pursue specific findings made during the past funding period and focus her studies on regulation of alpha 1 integrin expression in hepatocytes, the relationship between alpha 1 integrin expression and growth control in hepatocytes and TGF-beta 1 induced suppression of the transformed phenotype. She hypothesizes that transformation in hepatocytes is accompanied by loss of alpha 1 integrin expression which may be mediated by increased expression of ras, and that suppression of the transformed phenotype in hepatocytes induced by TGF-beta may be mediated, at least in part, by restoration of alpha 1 integrin expression. The specific aims are: (1) To examine regulation of expression of alpha 1 integrin in hepatocytes and hepatocyte cell lines; (2) To determine whether alpha 1 integrin expression plays an active role in growth control; (3) To elucidate key players in the signal transduction pathway used by TGF-beta to suppress the transformed phenotype; (4) To determine whether the type II/type I TGF-beta receptor ratio is related to the differential responses to TFG-beta observed in hepatocytes and hepatocyte cell lines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF MICROVASCULAR PERMEABILITY BY NITRIC OXIDE Principal Investigator & Institution: Rumbaut, Rolando E.; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): The overall goal of this research program is to understand physiologic regulation of microvascular permeability, an important determinant of nutrient delivery to tissues. Nitric oxide (NO) is a major regulator of local blood flow and pressure; recent studies support a role of NO in regulation of permeability. Determining how NO regulates permeability is complicated by recent data from this laboratory that challenge the traditional models of vascular transport pathways. The data reveal that while NO can modify flux of volume and of the serum protein, albumin, transport of albumin may occur through selective pathways that contribute little to movement of water and other solutes. A novel approach will be used to determine whether selective albumin transport occurs in vivo, basally and upon stimulation with NO and cyclic guanosine monophosphate (cGMP, a downstream signaling molecule for NO). The data also support that NO may interact with blood elements in regulation of permeability. Three aims will address unresolved questions of how NO regulates permeability: 1) Which vascular transport pathways are regulated by NO and cGMP? We hypothesize that NO and cGMP enhance volume and solute flux through convective pathways, without affecting selective albumin transport. 2) Which cell signaling mechanisms are responsible for regulation of solute transport pathways by NO? We hypothesize that NO enhances microvascular convective solute flux by acting through cGMP and cGMP-dependent protein kinase. 3) Which blood cells interact with NO in regulation of permeability? We hypothesize that neutrophils, and not platelets, mediate microvascular permeability responses to NO. Broader knowledge of
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physiologic regulation of microvascular permeability will help understand pathologic alterations in permeability in conditions such as sepsis, acute respiratory distress syndrome and ischemia-reperfusion injury. The long-term goal is to apply the knowledge gained from these studies to allow optimal management of patients with these important clinical entities and their associated microvascular alterations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE HEPATIC NEGATIVE ACUTE PHASE RESPONSE Principal Investigator & Institution: Denson, Lee A.; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-MAY-2000; Project End 31-MAR-2005 Summary: (adapted from the application) Dr. Denson will devote the majority of his time to clinically-oriented basic research. This award will provide for protected time for research, additional didactic training, and the purchase of reagents. It will support pursuit of the immediate research aims, as well as the establishment of an independent laboratory. The Department of Pediatrics has assured that 80% of Dr. Denson's time over the next five years will be dedicated to research activities. The hepatocyte's response to cytokines includes a reduction in the synthesis of key metabolic proteins; this constitutes the negative acute phase response (APR). Adverse clinical consequences include impairments of linear growth, hepatocyte transport, and glucose and drug metabolism, due to down-regulation of regulatory genes. The primary objective of this proposal will be to determine the cytoplasmic signaling mechanisms by which cytokines suppress expression of clinically important hepatic genes, including the growth hormone receptor and albumin. Our prior studies have demonstrated suppression of hepatocyte transporter and albumin promoter-driven luciferase activity by tumor necrosis factor alpha (TNF-a) or interleukin-1 Beta (IL-1B). Retinoid response elements have been shown to mediate coordinate reduction of hepatocyte transporter expression by IL-1B and ceramide. The goal of AIM I will be to identify cytokine response elements and associated transcription factors which regulate growth hormone receptor and albumin expression in HepG2 cells and primary rat hepatocytes. The goal of AIM 2 will be to characterize the cytoplasmic signal transduction mechanisms mediating cytokine suppression of these transactivators and associated target genes. Initial studies will define the role of ceramide signaling in acute phase down-regulation of these genes. The goal of AIM 3 will be to confirm the significance of cytokine signaling pathways identified in Aims I and 2 to in vivo acute phase gene regulation. Wild type and IL-1B and TNF-a receptor deficient mice will be treated with endotoxin and effects upon cytoplasmic signaling proteins and target regulatory transactivators and genes will be determined. Clarification of these molecular mechanisms will contribute to a broader understanding, of the regulatory links between several important hepatic metabolic pathways in both health and disease, and may ultimately lead to more specific treatments for cytokine-induced complications of inflammatory diseases such as linear growth failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RENAL DISEASE PROGRESSION IN AFRICAN AMERICANS Principal Investigator & Institution: Schelling, Jeffrey R.; Associate Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 03-SEP-2002; Project End 31-JUL-2006
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Summary: (provided by applicant): Diabetic nephropathy (DN) is the leading cause of chronic renal disease in the world. Though some modifiable risk factors have been identified, data from Caucasians and Pima Indians indicate that DN is genetically determined. The Wake Forest University (WFU) group has demonstrated that African Americans (AA) are at greater risk for DN compared to Caucasians. To identify DN susceptibility loci, the Case Western Reserve University (CWRU) and WFU groups are conducting NIH-funded projects and participating in the NIH-sponsored Family Investigation of Nephropathy and Diabetes (FIND) consortium. In contrast to these studies, which categorize subjects by discrete phenotypes, unraveling the genetic basis of complex diseases may be more easily accomplished through alternative strategies that include deconstructing phenotypes into continuous, quantitative traits. Building on our existing studies, we hypothesize hat the intermediate phenotypes, proteinuria and glomerular filtration rate (GFR) change, which respectively predict and measure progression of diabetic nephropathy to ESRD, are heritable. The hypothesis will be tested in a longitudinal study of AA and Caucasian families, which will permit the natural history of DN in AA to be defined for the first time. Data will be generated by quantitative trait locus (QTL) analysis, which offers advantages to the ongoing strategies, including enrollment and better definition of the clinical course of DN subjects with intermediate phenotypes (e.g. microalbuminuria), which have previously been excluded in our ongoing genetic analyses. Our specific aims are (1) AA and Caucasian families will be ascertained through index cases already enrolled in the FIND study with ESRD secondary to DN. Their diabetic siblings (n = 1200, about 60% AA) will be phenotyped and followed longitudinally. Dependent outcomes will include yearly urine albumin excretion and GFR measurements, (2) to assess association of genomic regions with the intermediate, quantitative phenotypes of proteinuria and GFR change, molecular and statistical methods will be used to examine regions suggestive of linkage with DN, which have been identified by the FIND genome scan. Cases and controls will be compared using both univariate and multivariate approaches. Environmental correlates will be included in the models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESISTANCE TRAINING DURING MAINTENANCE DIALYSIS Principal Investigator & Institution: Sceppa, Carmen C.; Nutrition Exercise Physiology Sarcopenla (Neps) Lab; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2005 Summary: (provided by applicant): There is a rising incidence of kidney failure in the US, with poor outcomes and high cost. End-stage renal disease (ESRD) affects almost 375,000 individuals in the US at a cost of more than $14 billion per year. Despite advances in dialysis and transplantation therapies, kidney failure leads to poor outcomes, poor prognosis and high health care costs. Malnutrition and the underlying systemic inflammatory response developed during the course of chronic kidney disease, worsen during ESRD, and leads to adverse outcomes, increased morbidity and mortality. Muscle wasting, impaired functional capacity and poor quality of life are the most important factors associated with malnutrition and inflammation in renal failure. We have shown in pre-dialysis patients with moderate chronic renal insufficiency that the anabolic effects of resistance exercise training result in significant improvements in protein utilization, nutritional status and functional capacity even in the context of anorexia and prescribed low protein diets. Thus, we propose to develop, test and implement a progressive resistance exercise routine for ESRD patients during the hemodialysis session. Our hypotheses are that the addition of 30-45 min of resistance
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exercise training during the dialysis session will counteract the burden of renal disease and will result in: 1) A feasible and safe exercise modality for ESRD patients (6-wk feasibility phase tested in 10 patients); 2) Net anabolism as evidenced by: improved nutritional status (i.e. increased protein catabolic rate, muscle mass and muscle strength); and reduced systemic inflammatory response (i.e. reduced C-reactive protein and interleukin-6, and increased serum albumin levels) compared to a randomly assigned control group on hemodilaysis but not exercise training (6-mo efficacy phase tested in 20 patients/group); and that 3) Improved self-reported physical function (i.e. increased SF-36 physical component scale) observed with resistance training will be associated with the improvements in nutritional status and inflammatory response. The long-term goal is to implement resistance exercise training routines during hemodialysis to overcome the underlying malnutrition and inflammation of ESRD and to improve disease outcome and prognosis. By implementing such intervention, we hope to offer a therapeutic strategy that can be incorporated to the standard of care of ESRD patients by working in conjunction with the dialysis unit staff. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE DEVELOPMENT
OF
WNT/BETA-CATENIN
SIGNALING
IN
LIVER
Principal Investigator & Institution: Monga, Satdarshan P.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Significant similarities exist in the mechanisms of development & cancer. Wnt/beta-Catenin & HGF/Met signaling pathways have been shown to play an important role in embryogenesis and carcinogenesis. We have previously demonstrated significance of beta-catenin in regulated liver growth during regeneration following two-third partial hepatectomy & in embryonic liver cultures. Aberrations in this pathway resulting in stabilization & redistribution of beta- catenin protein, due to mutations in beta-catenin, axin, GSKbeta & other unidentified reasons, have been demonstrated in unregulated liver growth in hepatocellular cancers & hepatoblastomas. We have also reported a cross talk between the Wnt & HGF pathways in liver owing to a novel association between beta-catenin & Met, a tyrosine kinase HGF receptor. HGF induced tyrosine phosphorylation dependent nuclear translocation of beta-catenin by triggering the dissociation of Met-beta-catenin complex at the hepatocyte membrane. Our hypothesis is that understandinq the regulation of these 2 pathways in liver development & reqeneration will be imperative to comprehend their roles in liver cancer with possible proqnostic, diaqnostic or therapeutic implications. We plan to examine these pathways using several existing models. An ontogenic analysis of beta-catenin & antisense studies in ex vivo embryonic liver cultures has revealed its important role during early liver development. This analysis has also demonstrated a tight temporal regulation of beta-catenin during liver development & it is lost in the liver after E16 stage. We will examine Met-beta-catenin & tyrosine phosphorylation dependent regulation of beta-catenin during liver development, regeneration & in primary hepatocyte cultures (with & without matrigel). Secondly, we have generated transgenic mice overexpressing non-mutant beta-catenin in liver, utilizing an albumin promoter. Characterization of these animals will enable us to examine the impact of beta-catenin deregulation on proliferation, apoptosis, stem cell compartment & lineage specification during liver development. These animals will be also utilized to perform partial hepatectomy studies to examine the effect of elevated beta-catenin protein on liver growth. Microarray analysis on transgenic livers will be useful to determine liver-
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specific target genes of this pathway. Thirdly, we have acquired beta-catenin floxed & albumin-cre mice that are now being used to generate beta-catenin conditional knockout mice. These will be characterized for understanding the in vivo role of beta-catenin in liver development by a thorough analysis. The ex vivo culture system will utilize livers from such mice for further characterization, analysis & intervention. Thus this study will be a comprehensive analysis of Wnt/beta-catenin pathway and its interactions with HGF in liver development & growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SOMATIC CELL GENE THERAPY AND NITROGEN FLUX IN UREA CYCLE PATIENTS Principal Investigator & Institution: Lee, Brendan; Associate Professor; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: The group of inborn errors of hepatic metabolism continue to be a prominent cause of mental retardation because of ineffective treatment strategies. Gene replacement therapy offers the theoretic advantage of correcting the basic protein deficiency. However, progress in hepatocyte directed gene therapy has been limited by questions involving pathophysiologic processes, choice of promoter and vector delivery system, route of delivery, host immune clearance, duration of expression, availability or small and large animal disease models, and quantitative measures of clinical efficacy. The three parts of this proposal attempt to address some of these issues using the group of urea cycle defects a model system. The first goal is to better understand the pathophysiologic disturbances in patients with urea cycle defects by correlating genotype and clinical severity with in vivo measurement of nitrogen flux and ureagenesis, while also developing a quantitative measure for future in vivo gene therapeutic interventions in both animal and humans. Flux through the urea cycle pathway will be measured by quantifying the conversion of [15/N-amide]glutamine to [15/N] urea. This flux will be correlated with genetic status (homozygosity, heterozygosity, hemizygosity), nature of mutation (null versus hypomorphic), and clinical severity (neonatal versus later presentation) in affected patients, heterozygous family members, and normal controls. In the second part of the study, the relative safety and efficacy of first generation (E1a deleted) and second generation (E1a/E2a deleted and all coding sequence deleted) adenovirus vectors will be determined after intravenous (i.v.) delivery in animals. In addition, potential avenues permitting long term transgene expression will be investigated. The efficacy of transient immunosuppression for the readministration of viral vectors will be evaluated, and the potential use of mariner transposon elements in mediating transgene integration in a host mammalian genome will be studied. In the third part, the urea cycle disorders, specifically murine and bovine models of citrullinemia, will be used a model systems in applying these basic findings to a clinical setting. The efficacy of the hybrid, ubiquitously active, CAG and liver-specific human albumin promoters will be compared in vivo. These data will form the preclinical basis for designing phase I clinical trials involving gene therapy in urea cycle patients. These results together will also be more generally applicable to other inborn errors of hepatocyte metabolism and to the production of extracellular products by hepatocytes. Early and long term biochemical correction would be expected to greatly decrease the great neurologic morbidity associated with these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SRC REGULATION OF LUNG ENDOTHELIAL BARRIER FUNCTION Principal Investigator & Institution: Minshall, Richard D.; Biomedical & Therapeutic Sci; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Loss of endothelial barrier function is important in the development of Adult Respiratory Distress Syndrome. The transcellular transport of albumin and other macromolecules via endothelial caveolae is a factor regulating endothelial barrier function. Using pulmonary microvascular endothelial cells, we have identified specific interactions between caveolin-1 and Src-family tyrosine kinases that may regulate albumin uptake and its transport via caveolae. The primary objective of the proposed investigation is to address the roles of caveolin-1 and Src in endocytosis and regulation of endothelial barrier function. Caveolin-1 and Src knockout mice will be used to investigate (1) the function of caveolin-1 in internalization of caveolae and transendothelial transport in pulmonary microvascular endothelial cells and (2) the role of dynamin in mediating fission of caveolae from the membrane and transcellular albumin permeability in endothelial cells. Our hypothesis is that Src-dependent phosphorylation of caveolin-1 and dynamin is essential for formation of caveolae and their scission from the membrane. We will measure vessel wall albumin permeability in the mouse lung preparation from caveolin-1 knockout mice. Mutant caveolin-1, Src, and dynamin cDNA constructs will be used in cell culture experiments to examine the role of Src-dependent interactions in regulating caveolin-1 and dynamin functions. Cholera toxin subunit B and albumin endocytosis and transcellular transport will be determined by electron microscopy, confocal microscopy, and measurement of iodinated tracers in cultured cells. Molecular-genetic and biochemical strategies will be used to elucidate the domain-specific and phosphorylation-dependent interactions between caveolin-1, Src, and dynamin. Thus, these studies will elucidate the Src-dependent signaling mechanisms that regulate endocytosis and transport across the pulmonary vascular endothelial barrier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRONG HEART FAMILY STUDY Principal Investigator & Institution: Maccluer, Jean W.; Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2002; Project Start 10-AUG-2000; Project End 31-MAY-2005 Summary: The long-term goal of the Strong Heart Family Study is to detect and map polymorphic genes that influence variation in risk factors for cardiovascular disease and other related disorders that are major health problems in American Indians. Of immediate interest are risk factors and precursors such as plasma concentrations of lipoproteins, apolipoproteins, insulin, glucose, urine albumin excretion, measures of obesity, measures associated with hemostasis, and measures of cardiac and arterial structure and function. In the pilot study during the current grant period, we have collaborated with the other Strong Heart Study (SHS) investigators in successfully recruiting and examining more than 300 members of extended families in each of the three centers (in Arizona, Oklahoma, and the Dakotas). We have shown that many of the CVD-related phenotypes are heritable, and we are generating a 10 centimorgan map that we are using in preliminary linkage analysis to localize CVD risk factor genes. We are encouraged by the success of the pilot study. To provide adequate power to detect and map CVD risk factor genes in each center and to localize genes that are important across tribal groups, we propose to recruit 900 additional members of approximately 30
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extended families in each center, ascertained through SHS participants. We will estimate heritabilities, effects of covariates, household and center effects, and genetic and environmental correlations for a large set of CVD risk factor phenotypes. We will generate a 10 centimorgan map that includes genotyping of 386 short tandem repeats (STRs) in each of the 2700 individuals, and screen the phenotypes for linkage using a variance component approach. We will do finer scale mapping with additional STRs to more precisely localize quantitative trait loci (QTLs) within targeted chromosomal regions, and use SNPs in positional candidate genes for linkage/association analysis to identify genes that are responsible for linkages detected by the initial genome scan. The Southwest Foundation investigators will continue to direct the design of the Family Study, will identify families to recruit, will serve as a resource for questions concerning recording of family data, directions in which to expand families, etc., and will be responsible for genotyping and statistical genetic analysis. This study will form the basis for future studies aimed at identifying and characterizing the genes that influence CVD risk factors in American Indians. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL BASIS OF INSULIN MIMETIC EFFECT OF VANADYL Principal Investigator & Institution: Makinen, Marvin W.; Professor; Biochem and Molecular Biology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2004 Summary: A new approach to identify the molecular species in the blood stream responsible for insulin-mimetic activity of organic chelates of the vanadyl (V02+) ion will be developed through application of electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopy. Since bis(acetylacetonato)oxovanadium(IV), bis(maltolato)oxovanadium(IV), and bis(3methyl- acetylacetonato)oxovanadium(IV) exhibit markedly enhanced insulin- mimetic activity over that of vanadyl sulfate, these compounds will be characterized by EPR and ENDOR spectroscopy to determine whether specific molecular adducts are formed with the major serum transport proteins albumin, transferrin, or transthyretin. Metabolic assays of insulin mimetic activity will be made with use of differentiated 3T3-L1 adipocytes. The level of insulin-mimetic activity of the chelated complexes and their protein adducts will be compared. Experiments will be carried out to determine whether the stoichiometry of V02+- chelates bound to each of the transport proteins can be correlated with the relative concentrations of the V02+-complex and the transport protein that elicit maximum activity in cell assays. Preliminary results already indicate that bis(acetylacetonate)oxovanadium(IV) binds to albumin as a 1:1 adduct and that this ratio of V02+-complex : albumin in cell assays is associated with maximal insulinmimetic activity. Initial studies will be directed to determine the influence of V02+chelates on the relative amounts of radioactive glucose incorporated into glycogen and lipid and how this may differ for insulin and other insulin mimetic agents. The threedimensional structure of V02+-Chelates both free in solution and bound to serum transport proteins will be determined by ENDOR spectroscopy with use of bis(acetylacetonato)oxovanadium(IV) synthetically enriched with carbon-13 or deuterium. The hyperfine (hf) couplings of the vanadium(IV) center with nearby magnetic nuclei will be analyzed to assign the relative positions of the nuclei with respect to the magnetic axes of the V02+ ion. The coordination structure and ligand geometry of the central V02+ ion for each complex will be modeled according to ENDOR distance constraints. We shall assign by ENDOR the types of protein residues that coordinate the metal ion in binding to proteins and determine whether protein
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residues have displaced chelate atoms or altered their geometry upon adduct formation. Of particular interest is the recent identification in this laboratory of two reversible ionizations that govern in aqueous solutions a pH dependent_distnbution of these V02+-chelates into four spectrally distinguishable species. Since these protonation processes appear to be associated with-hydrogen bonding of solvent molecules to either equatorial or axial oxygens, they may be important in displacement of chelate by protein residues by perturbation of the tautomeric equilibrium of the acac ligand. We shall therefore endeavor to assign the location of the protonatable group by ENDOR spectroscopy with use of perdeuterated V02+-chelate to remove overlapping resonances of nearby organic hydrogens. Since the V02+- chelates and their protein adducts are paramagnetic, these studies may lead to development of a new spectroscopic probe to characterize macromolecular interactions at the subcellular level that oven glucose uptake and metabolism in cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL CELL BIOLOGY IN CARDIOVASCULAR DISEASE Principal Investigator & Institution: Atkinson, David N.; Professor; Physiology and Biophysics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 31-DEC-2005 Summary: The objective of this program is to understand the Structural Biology of the macromolecular complexes involved in the transport of lipids into and out of cells. The aims of the project are: to define the 3-dimensional structures of cellular receptors and their ligands bound to LDL (Project 1): to study the formation of primordial nascent triglyceride-rich particles in the endoplasmic reticulum and understand how the secondary and tertiary structures of the N-terminal 41% apo-B regulates this process (Project 2); to understand the structure and conformation of apo-B, the 3- dimensional structure of LDL, the organization of apo-B on LDL, and to define the formation and 3dimensional structure of exchangeable apolipoproteins on nascent ans plasma HDL (Project 3); to understand the binding of fatty acids to albumin, the transfer of fatty acids from albumin and movement across membranes into cells, structural and dynamic features of intracellular fatty acid binding proteins, and the effect of fatty acids on intracellular Ph (Project 4). State-of-the-art techniques of structural biology are used to study isolated or reconstituted macromolecular complexes. Low resolution structures of individual particles (and/or 2 dimensional arrays) often decorated with site specific labels are obtained by electron microscopy, in particular cryo-EM, combined with image analysis and reconstruction. Detailed structures of individual proteins or protein-lipid complexes are determined by x-ray crystallography. The solution structure of peptides that model regions of proteins or small proteins such as the intracellular fatty acid binding proteins are determined by multi-dimensional NMR. High resolution molecular arrangements can be superimposed onto the low resolution structure of macromolecular assemblies obtained by electron microscopy to generate a "higher resolution" macromolecular structure. These studies can provide the biological structures involved in the processes by which lipids are moved into, within, and out of cells. Such information will allow the development of new molecular based strategies to control hyper beta lipoproteinemia, fatty acid-induced cellular damage in ischemia, and arteriosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Albumin
Project Title: THERAPY HOMOCYSTEINEMIA
IN
DIALYSIS
HYPOALBUMINEMIA
AND
Principal Investigator & Institution: Eustace, Joseph A.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (Adapted from the application) End stage renal disease is associated with several complex nutritional problems. Hypoalbuminemia, the strongest predictor of mortality on dialysis, is related to a combination of nutritional, inflammatory and comorbid factors, but the relative importance of these factors has not been prospectively evaluated. Relative vitamin deficiencies, especially that of B6, B12 and folate, also occur. Hyperhomocysteinemia (hyperHcy), a novel cardio-vascular and thrombotic risk factor, is at least partly correctable with folate and vitamin B6 and B12 supplementation but the clinical benefits of this therapy is not established. The projects outlined in this application will allow Dr. Eustace to continue his mentored research into these two major nutritional problems, hypoalbuminemia and hyperHcy. The PI will: (1A) Conduct a longitudinal analysis of risk factors for dialysis-associated hypoalbuminemia focusing on protein intake and inflammation (C-Reactive Protein), using data collected in the CHOICE cohort study. This is a nationally representative cohort of 925 incident dialysis patients in its 5th year of follow-up, headed by Drs. Powe, Klag and Coresh. (1B) Build on a clinical trial, he recently completed, by conducting a two-center, 2 x 2 factorial trial of 280 recently hospitalized hemodialysis patients, with serum albumins of less then 4.0 g/dl, examining in one arm of the trial the efficacy of oral essential amino acids supplements versus placebo at improving serum albumin levels and reducing hospitalization rates and (1C) Use a decision analysis model to compare the costeffectiveness, utility and outcomes of oral supplements versus alternative management strategies, including parenteral nutrition, naso-gastric feeding and anabolic agents. (2A) Compare, in the second arm of the above clinical trial, the efficacy of high versus standard dose folate, B6 & B12 supplementation at reducing all cause cardiovascular endpoints and vascular access thromboses. (2B) Perform a meta-analysis of published trials of the benefit of vitamin therapy on actual patient survival. This combination of observational and experimental research under the mentorship of Drs. Coresh and Klag, combined with didactic course work, in the supportive context of the Welch Center will allow Dr. Eustace to build on his current theoretical knowledge, make the transition into an independent clinical scientist and prepare him for a career investigating the role of nutrition in renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSPORT OF TNFALPHA ACROSS THE BBB Principal Investigator & Institution: Pan, Weihong; Neuroscience; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The blood-brain and blood-spinal cord barriers (BBB/BSCB), lying between the CNS (brain and spinal cord) and its supplying capillary blood vessels, provide an immense interface for interaction and exchange of information between the CNS and the rest of the body. We have shown that the BSCB is not static or physically passive, but undergoes dynamic changes, to regulate the availability of the cytokine tumor necrosis factor a (TNFa) from blood to the CNS. In the proposed studies, we will test the hypothesis that TNFa, after being transported across the BBB/BSCB, can facilitate functional recovery after spinal cord injury (SCI). We will also characterize the
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mechanisms by which this specific transport can be regulated. To determine the functional implications of TNFe transport, we will first show that spinal cord uptake of radioactively labeled TNFe will increase specifically in a modified mouse model of thoracic hemisection, and that this increase will not coincide with passive disruption of the barrier (measured by increased paracellular permeability of albumin). We will then determine the effects of TNFa treatment by evaluating locomotor behavior, intraspinal conduction of evoked potentials, and histological evidence of long tract regeneration. We expect that small doses of TNFa will facilitate recovery whereas large doses will worsen the deficits resulting from SCI. To identify the roles of p55- and p75-receptors, we will study TNFa transport in the presence of receptor antibodies and in the receptor knockout mice. We predict that increased spinal cord uptake of TNFe after SCI will be dependent upon upregulation of the receptors, as determined by Western blot and quantitative PCR analysis. Since transcytosis of a cytokine across the BBB/BSCB is a complicated process involving not only the receptors but also other regulatory proteins, we will identify novel transport regulatory proteins by co-immunoprecipitation, comparative proteomics, transfection and transport assays. We predict that the transport process will be regulated by the receptors, vesicular and cytoskeletal proteins, and chaperons in different phosphorylation states. By completing the proposed study, we will better understand the dual roles of TNFa in SCI and in its transport process involving the regulatory proteins. These transporters could be novel drug targets and therefore provide promising therapeutic potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: URINARY COLLAGEN IV IN DIABETIC GLOMERULOSCLEROSIS Principal Investigator & Institution: Shearman, Clyde W.; Vice President; Exocell, Inc. 3508 Market St, Ste 420 Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The objective of this project is to submit an application to the FDA for approval of a new in vitro diagnostic for quantitative measurement of urinary type IV collagen to assess risk for progressive decline in renal function in patients with diabetes. Currently, the measurement of urinary albumin is the only in vitro diagnostic approved by the FDA for assessment of early diabetic renal disease. Although microalbuminuria has become the established predictive marker for the development of diabetic nephropathy, not all patients with microalbuminuria progress to overt nephropathy with rising serum creatinine, and some patients progress without antecedent microalbuminuria. Recent studies in the diabetic db/db mouse indicate that urinary collagen IV becomes elevated as renal involvement progresses, coinciding with morphometric evidence of glomerular mesangial matrix expansion and reflecting the transition from leaky (albuminuric) to occluded glomeruli in which filtration surface area is reduced. In a survey of samples from human diabetic patients and using a sensitive and specific enzyme linked immunoassay constructed for this purpose, we have found that an elevated urinary collagen IV significantly correlates with declining filtration function, assessed by the reciprocal of the serum creatinine, but does not correlate with albumin excretion. The Specific Aims of Phase I, which will constitute milestones, are to: 1) Conduct a cross-sectional survey of 100 patients with type 1 diabetes, 100 patients with type 2 diabetes, and 50 patients with glomerular disease due to causes other than diabetes with respect to urinary collagen IV, amount of albumin excretion, and renal function assessed by the reciprocal of the serum creatinine (RSC); and 2) Begin refinement of the collagen IV immunoassay to ensure sensitivity, specificity, and ease of performance in a routine laboratory setting. The major goals in
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Phase II of this project are to: a) complete optimization of the immunoassay; b) define its performance characteristics; c) determine in prospective studies whether changes in filtration function over a two year period correlate with baseline and/or interim collagen IV excretion levels and compare the predictive values of urinary collagen IV versus albumin in this regard; and d) to assemble the data and prepare an application to the FDA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE OF NMR TO MEASURE TUMOR AND NORMAL TISSUE METAB DURING TUMOR ACIDIFICATION Principal Investigator & Institution: Glickson, Jerry D.; Research Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: This subcontract to Project 4 will examine metabolic and physiological aspects of acidification of human melanoma xenografts that are amenable to noninvasive measurement by magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). These methods will be applied to animals supplied by Dr. Leeper's laboratory to test the hypothesis that NMR can non-invasively detect tumor specific changes in extracellular and intracellular pH (pHe and pHi, respectively) induced by hyperglycemia and by hyperglycemia plus inhibition of oxidative metabolism (with meta- iodobenzylguanidine, MiBG), and/or by hyperglycemia plus inhibition of the Na+/H+ cation exchanger (with Cariporide mesilate, HOE642) and the HCO3- /Cl-anion exchanger (with 4,4-diisothiocyanstilbene 2,2-disulphonic acid, DIDS). In addition, it is proposed that NMR can help delineate the underlying mechanism of acidification by hyperglycemia plus regulatory inhibition. To test this hypothesis, 31P MRS will be employed to measure the pHi and pHe in the tumor, in host muscle, and brain under conditions of normoglycemia, hyperglycemia plus MIBG and/or HOE642 plus DIDS. Inorganic phosphate (Pi) and 3-aminopropylphosphonate will serve as indicators of pHi and pHe, respectively. To test the hypothesis that tumor acidification under conditions of hyperglycemia and hyperglycemia plus respiratory inhibition is mediated by production of lactic acid (i.e., glycolysis), steady state lactate concentrations will be monitored on 1H MRS employing a selective multiple quantum coherence transfer pulse sequence developed by the subcontractor's laboratory to edit out the lactate resonance from interfering lipid resonances. Further insight into the mechanism of tumor acidification under conditions of hyperglycemia +/- respiratory inhibition will be obtained by measuring flux through the glycolytic pathway and through the TCA cycle from the kinetics of 13C-labeling of lactate and glutamate, respective, following infusion of [1-13C]glucose. The spatial distributions of 13C-labeled glucose and lactate in the tumor at isotope steady state (for glucose) will be imaged by 13C chemical shift imaging at constant concentrations of labeled glucose in the blood (19+/-) mM), and the vascular volume distribution will be imaged by dynamic 1H MRI using Gd-DTPAalbumin as a vascular marker. Images will be correlated with histology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VALIDATION OF BIOMARKERS IN HUMANS EXPOSED TO PAHS Principal Investigator & Institution: Qu, Qingshan; Assistant Professor; Environmental Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2004
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Summary: (provided by applicant): Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants due to significant contributions from incomplete combustion of fossil fuels and other organic materials. Exposure to PAHs has been associated with lung and skin cancer in occupational setting and a potential increased risk of cancer in humans exposed to PAHs at low ambient levels is now becoming a major public concern. In order to address this problem, a variety of biomarkers have been developed to index the exposure levels or biological effects of PAHs. However, the validity of their applications in risk assessment of PAHs at low levels is uncertain. This proposed study will mainly focus on validating these biomarkers in a Chinese population with broad ranges of exposures to PAHs. The biomarkers to be validated include urinary 1-hydroxypyrene, DNA and protein (hemoglobin and albumin) adducts as well as p53 protein. In addition, the polymorphisms of genes, including CYP1A1, microsomal epoxide hydrolase (mEH), GSTM1, and p53 genes, will be identified to assess gene-environment interactions. For this purpose, we will conduct a study with 5 projects included. The specific aims of this study are: (1) to determine if these candidate markers can at least reliably detect differences between workers with relatively high levels of exposure and unexposed subjects; (2) to examine the reproducibility of these biomarkers and to assess their interand intra-individual variabilities; (3) to estimate the effective half-lives of the exposure markers and to evaluate whether they relate to the most current exposure or to integrated exposures over a period of time; (4) to determine whether these markers can be reliably used to differentiate between unexposed subjects and exposed subjects at low ambient levels and to characterize their exposure-response relationships; (5) to investigate the specificity of these biomarkers and to identify possible effects of general confounding factors, such as smoking, diet, age, and gender on the levels of these markers; (6) To evaluate how gene polymorphisms of CYP1A1, GSTM1, mEH, and p53 interact with PAHs exposure in relation to the levels of all candidate biomarkers. The ultimate goal of this study is to determine whether or not these biomarkers can be useful as markers for risk assessment in humans exposed to PAHs at low ambient levels in future large scale epidemiological studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASCULAR ENDOTHELIAL GROWTH FACTOR INDUCED LUNG EDEMA Principal Investigator & Institution: Kaner, Robert J.; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Adult respiratory distress syndrome (ARDS) affects 150,000 individuals in the US annually with a mortality of 40 percent. Current treatment is supportive only. New therapies will require a detailed understanding of the molecular basis for this disorder. One of the earliest manifestations of ARDS is the development of noncardiogenic pulmonary edema. We have made the novel observation that pulmonary edema is induced by overexpression of the vascular endothelial growth factor (VEGF) gene in lung using a modified adenovirus vector approach. Gene transfer and overexpression of VEGF were confirmed by Northern analysis of mouse lung extracts and ELISA. Edema was observed in lung histology and quantified by lung wet-to-dry weight ratio and pulmonary capillary permeability to macromolecules by the Evan's blue dye assay and 131 l-albumin lung leak. This proposal will fully characterize the mechanism of VEGF-induced pulmonary edema with regard to endothelial permeability, alveolar dysfunction, VEGF receptor(s)
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specificity, signal transduction pathways and downstream effectors that mediate the edema. Ultrastructual information will be obtained by electron microscopy of VEGFoverexpressing lungs. Structure-function relationships of VEGF isoforms to the development of pulmonary edema will be defined using Ad vectors containing the genes for the various VEGF isoforms as well as mutant VEGFs which have specificity for binding to a particular VEGF receptor. Overexpression, immunoinhibition and pharmacologic inhibitor studies will define the roles of potential mediators downstream from VEGF such as endothelial nitric oxide synthase and nitric oxide and the intracellular signaling pathways that are activated during VEGF-induced edema. Studies to assess the potential role of activated neutrophils as a source of VEGF in vivo during acute lung injury will be developed. Bronchoalveolar lavage and plasma levels of VEGF will be measured in patients with acute lung injury to develop the hypothesis that overexpression of VEGF in lung may be one mechanism favoring increased permeability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WISCONSIN EPIDEMIOLOGICAL STUDY OF CARDIOVASCULAR DISEAS Principal Investigator & Institution: Klein, Ronald; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: This proposal describes a population-based cohort aimed at determining the prevalence and incidence of cardiovascular disease morbidity and mortality in people with Type 1 diabetes of long-duration. For this epidemiologic study, subjects include all insulin-taking persons who: (1) were less than 30 years of age at the time of their diagnosis, (2) had received primary medical care in an 11-county area of south-central Wisconsin, and (3) were first identified in 1979-80. Standardized protocols for examinations and interviews have been employed during the baseline, 4-, 10-, and 14year follow up examinations. Refusal rates have been low. The mean age of the cohort and the long duration of diabetes provide an opportunity to document the prevalence and incidence of coronary heart disease, myocardial infarction, angina, congestive heart failure, stroke, transient ischemic attacks, peripheral vascular disease, and cardiovascular disease mortality in a large population-based group of persons with Type 1 diabetes. Retinal photographs of each study participant were taken at the baseline examination. This will permit us to test the predictive ability of focal and generalized retinal arteriolar narrowing and arterio-venous cross changes (i.e. A/V nicking) for subsequent macrovascular events controlling for other risk factors. These factors include blood pressure, cigarette smoking, serum lipids, body mass index, duration of diabetes, and glycemia. We plan to reexamine this cohort to obtain ECGs, blood lipid fractions not previously measured, and fibrinogen, as well as upper and lower extremity blood pressures, urine specimens, and medical records. This will provide information about silent about silent infarctions and other cardiographic abnormalities as well as previously doctor-diagnosed macrovascular events in longterm survivors of Type 1 diabetes. Study examinations will be performed in a mobile van. Participants will provide two urine specimens for determination of urinary albumin excretion. Fasting blood will be obtained for determination of glycosylated hemoglobin Alc, blood sugar, serum cholesterol, triglycerides, HDL- cholesterol, LDLcholesterol, VDL-cholesterol, LDL particle size, serum creatinine, and fibrinogen. Additional study procedures include measurements of weight and height, waist and hip girth, and brachial and ankle blood pressures. Electrocardiography will also be
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performed. A questionnaire will be administered Participants will subsequently be interviewed yearly and clinical and hospital records and death certificates will be collected to document new cardiovascular disease events. Findings regarding the prevalence and incidence of cardiovascular disease and associated risk factors will be of great public health importance in directing further at preventing these conditions in people with Type 1 diabetes of long duration. 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 “albumin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for albumin in the PubMed Central database: •
A domain of methylation change at the albumin locus in rat hepatoma cell variants. by Orlofsky A, Chasin LA.; 1985 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=366696
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A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. by Watkins S, Madison J, Davis E, Sakamoto Y, Galliano M, Minchiotti L, Putnam FW.; 1991 Jul 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52001
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A fifth 2S albumin isoform is present in Arabidopsis thaliana. by van der Klei H, Van Damme J, Casteels P, Krebbers E.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=160676
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A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes. by Costa RH, Grayson DR, Xanthopoulos KG, Darnell JE Jr.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280315
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A low-protein diet restricts albumin synthesis in nephrotic rats. by Kaysen GA, Jones H Jr, Martin V, Hutchison FN.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303869
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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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A Monoclonal IgM Protein with Antibody-like Activity for Human Albumin. by Hauptman S, Tomasi TB Jr.; 1974 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333076
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A nucleotide insertion and frameshift cause analbuminemia in an Italian family. by Watkins S, Madison J, Galliano M, Minchiotti L, Putnam FW.; 1994 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43353
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A seven-base-pair deletion in an intron of the albumin gene of analbuminemic rats. by Esumi H, Takahashi Y, Sato S, Nagase S, Sugimura T.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=393316
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Abnormal fibrinogens IJmuiden (B beta Arg14----Cys) and Nijmegen (B beta Arg44---Cys) form disulfide-linked fibrinogen-albumin complexes. by Koopman J, Haverkate F, Grimbergen J, Engesser L, Novakova I, Kerst AF, Lord ST.; 1992 Apr 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48891
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Absence of albumin mRNA in the liver of analbuminemic rats. by Esumi H, Okui M, Sato S, Sugimura T, Nagase S.; 1980 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349585
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Activation of chromosomal vitellogenin genes in Xenopus oocytes by pure estrogen receptor and independent activation of albumin genes. by McKenzie EA, Cridland NA, Knowland J.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362945
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Adhesion of Listeria monocytogenes to silica surfaces after sequential and competitive adsorption of bovine serum albumin and beta-lactoglobulin. by alMakhlafi H, Nasir A, McGuire J, Daeschel M.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167467
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Albumin is encoded by 2 messenger RNAs in Xenopus laevis. by Schoenberg DR.; 1981 Dec 21; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=327633
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Albumin metabolism in patients with Whipple's disease. by Laster L, Waldmann TA, Fenster LF, Singleton JW.; 1966 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292741
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Albumin Metabolism: Effect of the Nutritional State and the Dietary Protein Intake. by James WP, Hay AM.; 1968 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297360
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Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. by Brennan SO, Myles T, Peach RJ, Donaldson D, George PM.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53192
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Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. by Tang S, Leung JC, Abe K, Chan KW, Chan LY, Chan TM, Lai KN.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151921
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Albumin to Ascites: Demonstration of a Direct Pathway Bypassing the Systemic Circulation. by Zimmon DS, Oratz M, Kessler R, Schreiber SS, Rothschild MA.; 1969 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297460
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Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. by Carlson J, Sakamoto Y, Laurell CB, Madison J, Watkins S, Putnam FW.; 1992 Sep 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49890
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Amino acid substitutions in albumin variants found in Brazil. by Arai K, Huss K, Madison J, Putnam FW, Salzano FM, Franco MH, Santos SE, Freitas MJ.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286796
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Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. by Takahashi N, Takahashi Y, Blumberg BS, Putnam FW.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305099
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Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. by Takahashi N, Takahashi Y, Isobe T, Putnam FW, Fujita M, Satoh C, Neel JV.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299464
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Analbuminemia: three cases resulting from different point mutations in the albumin gene. by Watkins S, Madison J, Galliano M, Minchiotti L, Putnam FW.; 1994 Sep 27; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44823
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Association of rheumatic fever with serum albumin concentration and body iron stores in Bangladeshi children: case-control study. by Zaman MM, Yoshiike N, Rouf MA, Haque S, Chowdhury AH, Nakayama T, Tanaka H.; 1998 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28708
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At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes, and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory. by Sorrentino D, Robinson RB, Kiang CL, Berk PD.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329794
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Binding of a liver-specific factor to the human albumin gene promoter and enhancer. by Frain M, Hardon E, Ciliberto G, Sala-Trepat JM.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360950
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Binding of Candida albicans to Immobilized Amino Acids and Bovine Serum Albumin. by Hawser SP, Islam K.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107869
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Brain protein kinase C phosphorylating poly(arginine,serine) or lamin B is stimulated by anions and by an activator purified from bovine serum albumin preparations. by Abdel-Ghany M, el-Gendy K, Zhang S, Raden D, Racker E.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286784
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Calcium-binding protein, parvalbumin, is reduced in mutant mammalian muscle with abnormal contractile properties. by Stuhlfauth I, Reininghaus J, Jockusch H, Heizmann CW.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=391581
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Catalysis of S-nitrosothiols formation by serum albumin: The mechanism and implication in vascular control. by Rafikova O, Rafikov R, Nudler E.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122876
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cDNA and Protein Sequence of Polymorphic Macaque Albumins that Differ in Bilirubin Binding. by Watkins S, Sakamoto Y, Madison J, Davis E, Smith DG, Dwulet J, Putnam FW.; 1993 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46096
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Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression. by Friedman JM, Babiss LE, Clayton DF, Darnell JE Jr.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=367140
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Chicken ovalbumin gene fused to a herpes simplex virus alpha promoter and linked to a thymidine kinase gene is regulated like a viral gene. by Post LE, Norrild B, Simpson T, Roizman B.; 1982 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=369781
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Cleavage properties of an estrogen-regulated polysomal ribonuclease involved in the destabilization of albumin mRNA. by Chernokalskaya E, Dompenciel R, Schoenberg DR.; 1997 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146505
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Comparison of albumin receptors expressed on bovine and human group G streptococci. by Raeder R, Otten RA, Boyle MD.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257801
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Competitive adsorption of human immunoglobulin G and albumin: consequences for structure and reactivity of the adsorbed layer. by Lutanie E, Voegel JC, Schaaf P, Freund M, Cazenave JP, Schmitt A.; 1992 Oct 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50239
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Complete Structure of the Human [alpha]-Albumin Gene, a New Member of the Serum Albumin Multigene Family. by Nishio H, Dugaiczyk A.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38784
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Conversion of [alpha]-lactalbumin to a protein inducing apoptosis. by Svensson M, Hakansson A, Mossberg AK, Linse S, Svanborg C.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18203
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Creation and phenotypic analysis of alpha-lactalbumin-deficient mice. by Stinnakre MG, Vilotte JL, Soulier S, Mercier JC.; 1994 Jul 5; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44239
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Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. by Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166163
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Debate: Albumin administration should be avoided in the critically ill. by Pulimood TB, Park GR.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137253
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Debate: Albumin administration should not be avoided. by Allison SP, Lobo DN.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137252
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Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. by Yeh P, Landais D, Lemaitre M, Maury I, Crenne JY, Becquart J, Murry-Brelier A, Boucher F, Montay G, Fleer R, et al.; 1992 Mar 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48562
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Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system. by Heard JM, Herbomel P, Ott MO, Mottura-Rollier A, Weiss M, Yaniv M.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=365374
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Differences in methylation patterns of the alpha-fetoprotein and albumin genes in hepatic and non hepatic developing rat tissues. by Tratner I, Nahon JL, Sala-Trepat JM.; 1988 Apr 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336431
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Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans. by De Feo P, Gaisano MG, Haymond MW.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295469
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DNA methylation: correlation with DNase I sensitivity of chicken ovalbumin and conalbumin chromatin. by Kuo MT, Mandel JL, Chambon P.; 1979 Dec 20; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342373
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DNA methylation: organ specific variations in the methylation pattern within and around ovalbumin and other chicken genes. by Mandel JL, Chambon P.; 1979 Dec 20; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342372
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Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat. by Franks JJ, Kirsch RE, Frith LO, Purves LR, Franks WT, Franks JA, Mason P, Saunders SJ.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370602
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Effect of Ovalbumin Aerosol Exposure on Colonization of the Porcine Upper Airway by Pasteurella multocida and Effect of Colonization on Subsequent Immune Function. by Hamilton TD, Roe JM, Hayes CM, Webster AJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95606
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Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/HeJ mice. by Moreau MC, Corthier G.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259643
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Efficient and Specific Ribozyme-Mediated Reduction of Bovine [alpha]-Lactalbumin Expression in Double Transgenic Mice. by L'Huillier PJ, Soulier S, Stinnakre M, Lepourry L, Davis SR, Mercier J, Vilotte J.; 1996 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39089
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EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia. by Teramoto T, Qiu J, Plumier JC, Moskowitz MA.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152938
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Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex. by Galarreta M, Hestrin S.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129463
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Elements within the beta-lactoglobulin gene inhibit expression of human serum albumin cDNA and minigenes in transfected cells but rescue their expression in the mammary gland of transgenic mice. by Barash I, Nathan M, Kari R, Ilan N, Shani M, Hurwitz DR.; 1996 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145689
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Energy transfer to a proton-transfer fluorescence probe: Tryptophan to a flavonol in human serum albumin. by Sytnik A, Litvinyuk I.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24028
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Enhanced methionine levels and increased nutritive value of seeds of transgenic lupins (Lupinus angustifolius L.) expressing a sunflower seed albumin gene. by Molvig L, Tabe LM, Eggum BO, Moore AE, Craig S, Spencer D, Higgins TJ.; 1997 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22931
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Eradication of Cryptosporidium parvum Infection by Mice with Ovalbumin-Specific T Cells. by Lukin K, Cosyns M, Mitchell T, Saffry M, Hayward A.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97473
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Evidence for a Role of the Microtubular System in the Secretion of Newly Synthesized Albumin and Other Proteins by the Liver. by Le Marchand Y, Patzelt C, Assimacopoulos-Jeannet F, Loten EG, Jeanrenaud B.; 1974 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302646
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Evidence for Covalent Binding of Acyl Glucuronides to Serum Albumin Via an Imine Mechanism as Revealed by Tandem Mass Spectrometry. by Ding A, Ojingwa JC, McDonagh AF, Burlingame AL, Benet LZ.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46392
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Exon skipping during splicing of albumin mRNA precursors in Nagase analbuminemic rats. by Shalaby F, Shafritz DA.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53748
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Familial hypercatabolic hypoproteinemia. A disorder of endogenous catabolism of albumin and immunoglobulin. by Waldmann TA, Terry WD.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329849
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Fatty Acid-Depleted Albumin Induces the Formation of Echovirus A Particles. by Ward T, Powell RM, Chaudhry Y, Meredith J, Almond JW, Kraus W, Nelsen-Salz B, Eggers HJ, Evans DJ.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111843
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Femtosecond studies of protein --ligand hydrophobic binding and dynamics: Human serum albumin. by Zhong D, Douhal A, Zewail AH.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18869
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Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer. by Bernier D, Thomassin H, Allard D, Guertin M, Hamel D, Blaquiere M, Beauchemin M, LaRue H, Estable-Puig M, Belanger L.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=359474
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Functional conversion of the homologous proteins alpha-lactalbumin and lysozyme by exon exchange. by Kumagai I, Takeda S, Miura K.; 1992 Jul 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49402
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Genetic variants of human serum albumin in Italy: point mutants and a carboxylterminal variant. by Madison J, Galliano M, Watkins S, Minchiotti L, Porta F, Rossi A, Putnam FW.; 1994 Jul 5; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44225
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Genetic variants of serum albumin in Americans and Japanese. by Madison J, Arai K, Sakamoto Y, Feld RD, Kyle RA, Watkins S, Davis E, Matsuda Y, Amaki I, Putnam FW.; 1991 Nov 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52819
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Heterogeneity of the 5' terminus of hen ovalbumin messenger ribonucleic acid. by Malek LT, Eschenfeldt WH, Munns TW, Rhoads RE.; 1981 Apr 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=326789
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Human albumin administration in critically ill patients: systematic review of randomised controlled trials. by Reviewers CI.; 1998 Jul 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28613
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Hydrophobic sequence minimization of the [alpha]-lactalbumin molten globule. by Wu LC, Kim PS.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24957
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Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene. by Brennan SO, Arai K, Madison J, Laurell CB, Galliano M, Watkins S, Peach R, Myles T, George P, Putnam FW.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54013
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Identical structural changes in inherited albumin variants from different populations. by Arai K, Ishioka N, Huss K, Madison J, Putnam FW.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286484
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Identification and Characterization of Subpopulations of Lymphocytes in Human Peripheral Blood after Fractionation on Discontinuous Gradients of Albumin THE CELLULAR DEFECT IN X-LINKED AGAMMAGLOBULINEMIA. by Geha RS, Rosen FS, Merler E.; 1973 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302448
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Identification of a Peptide from Mammal Albumins Responsible for Enhanced Pigment Production by Group B Streptococci. by Rosa-Fraile M, Sampedro A, Varela J, Garcia-Pena M, Gimenez-Gallego G.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103735
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Immunocytochemical localization of albumin in the secretory apparatus of rat liver parenchymal cells. by Yokota S, Fahimi HD.; 1981 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320312
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In vivo acceleration of heart relaxation performance by parvalbumin gene delivery. by Szatkowski ML, Westfall MV, Gomez CA, Wahr PA, Michele DE, DelloRusso C, Turner II, Hong KE, Albayya FP, Metzger JM.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=198873
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Incorporation of intravenously injected albumin, immunoglobulin G, and fibrinogen in guinea pig megakaryocyte granules. by Handagama PJ, Shuman MA, Bainton DF.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303955
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Increase of Skeletal Muscle Relaxation Speed by Direct Injection of Parvalbumin cDNA. by Muntener M, Kaser L, Weber J, Berchtold MW.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41546
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Increased endothelial albumin permeability mediated by protein kinase C activation. by Lynch JJ, Ferro TJ, Blumenstock FA, Brockenauer AM, Malik AB.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296668
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Increased nutritive value of transgenic potato by expressing a nonallergenic seed albumin gene from Amaranthus hypochondriacus. by Chakraborty S, Chakraborty N, Datta A.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16307
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Increased permeability across the blood-nerve barrier of albumin glycated in vitro and in vivo from patients with diabetic polyneuropathy. by Poduslo JF, Curran GL.; 1992 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48628
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Induction of albumin gene transcription in hepatocytes by extracellular matrix proteins. by Caron JM.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=361009
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Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver. by Grossman SB, Yap SH, Shafritz DA.; 1977 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372295
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Interaction between a "processed" ovalbumin peptide and Ia molecules. by Buus S, Colon S, Smith C, Freed JH, Miles C, Grey HM.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=323646
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Interaction between various polymerized human albumins and hepatitis B surface antigen. by Yu MW, Finlayson JS, Shih JW.; 1985 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255057
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Interactions of a very long chain fatty acid with model membranes and serum albumin. Implications for the pathogenesis of adrenoleukodystrophy. by Ho JK, Moser H, Kishimoto Y, Hamilton JA.; 1995 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185769
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Interdomain zinc site on human albumin. by Stewart AJ, Blindauer CA, Berezenko S, Sleep D, Sadler PJ.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152985
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Interference between Host Resistance to Listeria monocytogenes Infection and Ovalbumin-Induced Allergic Responses in Mice. by Mizuki D, Miura T, Sasaki S, Mizuki M, Madarame H, Nakane A.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98097
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Isolation and characterisation of the Xenopus laevis albumin genes: loss of 74K albumin gene sequences by library amplification. by May FE, Weber R, Westley BR.; 1982 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320656
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Isolation and Characterization of a Cell Surface Albumin-Binding Protein from Vascular Endothelial Cells. by Tiruppathi C, Finnegan A, Malik AB.; 1996 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40216
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Isolation and molecular characterization of a novel albumin-binding protein from group G streptococci. by Sjobring U.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257367
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Lactation is Disrupted by [alpha]-Lactalbumin Deficiency and Can be Restored by Human [alpha]-Lactalbumin Gene Replacement in Mice. by Stacey A, Schnieke A, Kerr M, Scott A, McKee C, Cottingham I, Binas B, Wilde C, Colman A.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42313
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Linkage analyses of murine immunoglobulin heavy chain and serum prealbumin genes establish their location on chromosome 12 proximal to the T (5;12) 31H breakpoint in band 12F1. by Meo T, Johnson J, Beechey CV, Andrews SJ, Peters J, Searle AG.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348310
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Locations of the three primary binding sites for long-chain fatty acids on bovine serum albumin. by Hamilton JA, Era S, Bhamidipati SP, Reed RG.; 1991 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51166
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M12 protein from Streptococcus pyogenes is a receptor for immunoglobulin G3 and human albumin. by Retnoningrum DS, Cleary PP.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186523
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Marked increases of two kinds of two-exon-skipped albumin mRNAs with aging and their further increase by treatment with 3'-methyl-4-dimethylaminoazobenzene in Nagase analbuminemic rats. by Kaneko T, Shima H, Esumi H, Ochiai M, Nagase S, Sugimura T, Nagao M.; 1991 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51307
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Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells. by Kamps JA, Morselt HW, Swart PJ, Meijer DK, Scherphof GL.; 1997 Oct 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23586
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Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. by Murray JC, Demopulos CM, Lawn RM, Motulsky AG.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=390195
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Murine Macrophages Use Oxygen- and Nitric Oxide-Dependent Mechanisms To Synthesize S-Nitroso-Albumin and To Kill Extracellular Trypanosomes. by Gobert AP, Semballa S, Daulouede S, Lesthelle S, Taxile M, Veyret B, Vincendeau P.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108487
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Muscle beta-actinin and serum albumin of the chicken are indistinguishable by physicochemical and immunological criteria. by Heizman CW, Muller G, Jenny E, Wilson KJ, Landon F, Olomucki A.; 1981 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318992
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Mutations in genetic variants of human serum albumin found in Italy. by Galliano M, Minchiotti L, Porta F, Rossi A, Ferri G, Madison J, Watkins S, Putnam FW.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=55031
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Newly synthesized RNA: simultaneous measurement in intact cells of transcription rates and RNA stability of insulin-like growth factor I, actin, and albumin in growth hormone-stimulated hepatocytes. by Johnson TR, Rudin SD, Blossey BK, Ilan J, Ilan J.; 1991 Jun 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51857
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No evidence for post-transcriptional control of albumin and alpha-fetoprotein gene expression in developing rat liver neoplasia. by Nahon JL, Gal A, Frain M, Sell S, SalaTrepat JM.; 1982 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320579
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Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth of Blastomyces dermatitidis Yeast Form In Vitro. by Giles S, Czuprynski C.; 2003 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=219601
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Nuclear export of phosphorylated C /EBP[beta] mediates the inhibition of albumin expression by TNF-[alpha]. by Buck M, Zhang L, Halasz NA, Hunter T, Chojkier M.; 2001 Dec 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125761
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Nucleosome positioning properties of the albumin transcriptional enhancer. by McPherson CE, Horowitz R, Woodcock CL, Jiang C, Zaret KS.; 1996 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145657
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Nucleotide sequence at the 5' end of ovalbumin messenger RNA from chicken. by Kuebbing D, Liarakos CD.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342161
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Osmotic pressure contribution of albumin to colloidal interactions. by Singh-Zocchi M, Andreasen A, Zocchi G.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21980
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Ovalbumin is synthesized in mouse cells transformed with the natural chicken ovalbumin gene. by Lai EC, Woo SL, Bordelon-Riser ME, Fraser TH, O'Malley BW.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348245
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Partial amino acid sequence homology between an heredofamilial amyloid protein and human plasma prealbumin. by Benson MD.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370661
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Parvalbumin gene transfer corrects diastolic dysfunction in diseased cardiac myocytes. by Wahr PA, Michele DE, Metzger JM.; 1999 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18398
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Photochemical protease: Site-specific photocleavage of hen egg lysozyme and bovine serum albumin. by Kumar CV, Buranaprapuk A, Opiteck GJ, Moyer MB, Jockusch S, Turro NJ.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27899
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Plasma Albumin is a Potent Trigger of Calcium Signals and DNA Synthesis in Astrocytes. by Nadal A, Fuentes E, Pastor J, McNaughton PA.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42532
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Platelet alpha-granule fibrinogen, albumin, and immunoglobulin G are not synthesized by rat and mouse megakaryocytes. by Handagama P, Rappolee DA, Werb Z, Levin J, Bainton DF.; 1990 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296872
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Point substitutions in albumin genetic variants from Asia. by Arai K, Madison J, Shimizu A, Putnam FW.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53291
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Point substitutions in Japanese alloalbumins. by Arai K, Madison J, Huss K, Ishioka N, Satoh C, Fujita M, Neel JV, Sakurabayashi I, Putnam FW.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297781
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Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA. by Esumi H, Takahashi Y, Sekiya T, Sato S, Nagase S, Sugimura T.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345826
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Pretreatment with Restriction Enzyme or Bovine Serum Albumin for Effective PCR Amplification of Epstein-Barr Virus DNA in DNA Extracted from Paraffin-Embedded Gastric Carcinoma Tissue. by Satoh Y, Takasaka N, Hoshikawa Y, Osaki M, Ohfuji S, Ito H, Kaibara N, Kurata T, Sairenji T.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105349
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Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. by Dwulet FE, Benson MD.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=344901
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Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin. by Pras M, Prelli F, Franklin EC, Frangione B.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=393414
Studies
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Protein degradation by ruminal microorganisms from sheep fed dietary supplements of urea, casein, or albumin. by Wallace RJ, Broderick GA, Brammall ML.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203750
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Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. by Davies RW, Staprans I, Hutchison FN, Kaysen GA.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296766
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Proximal tubule reabsorption after hyperoncotic albumin infusion. Role of parathyroid hormone and dissociation from plasma volume. by Knox FG, Schneider EG, Willis LR, Strandhoy JW, Ott CE, Cuche JL, Goldsmith RS, Arnaud CD.; 1974 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301492
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Quantitative assay for albumin-producing liver cells after simian virus 40 transformation of rat hepatocytes maintained in chemically defined medium. by Isom HC, Georgoff I.; 1984 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=391927
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Receptor in group C and G streptococci detects albumin structures present in mammalian species. by Wideback K, Seal US, Kronvall G.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351251
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Regulated nuclear polyadenylation of Xenopus albumin pre-mRNA. by Rao MN, Chernokalskaya E, Schoenberg DR.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146192
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Regulation of albumin gene expression in a series of rat hepatocyte cell lines immortalized by simian virus 40 and maintained in chemically defined medium. by Woodworth CD, Isom HC.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=368030
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Regulation of albumin gene expression in hepatoma cells of fetal phenotype: dominant inhibition of HNF1 function and role of ubiquitous transcription factors. by Rollier A, DiPersio CM, Cereghini S, Stevens K, Tronche F, Zaret K, Weiss MC.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=300900
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Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin. by Yamamoto N, Kumashiro R, Yamamoto M, Willett NP, Lindsay DD.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281327
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Relief of amplification inhibition in PCR with bovine serum albumin or T4 gene 32 protein. by Kreader CA.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167874
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Replacement of animal serum proteins by human albumin for growth and interferon production by Namalva cells. by Field AK, Scattergood EM, Hopke CJ, Tytell AA, Hilleman MR.; 1980 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352991
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Repression of the albumin gene in Novikoff hepatoma cells. by Capetanaki YG, Flytzanis CN, Alonso A.; 1982 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=369784
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Restriction fragment length polymorphism of the rat albumin gene in SpragueDawley rats and its application in genetic study of analbuminemia. by Esumi H, Takahashi Y, Sato S, Sugimura T.; 1982 Jul 24; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320797
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Role of bovine serum albumin in the nutrition of Mycobacterium tuberculosis. by Lynn M, Wilson AR, Solotorovsky M.; 1979 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=243590
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Role of Gingipains in Growth of Porphyromonas gingivalis in the Presence of Human Serum Albumin. by Grenier D, Imbeault S, Plamondon P, Grenier G, Nakayama K, Mayrand D.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98614
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Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity. by Caillard O, Moreno H, Schwaller B, Llano I, Celio MR, Marty A.; 2000 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27231
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Roles of bovine serum albumin and copper in the assay and stability of ammonia monooxygenase activity in vitro. by Juliette LY, Hyman MR, Arp DJ.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177264
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Rotavirus-specific antibodies in fetal bovine serum and commercial preparations of serum albumin. by Offit PA, Clark HF, Taylor AH, Hess RG, Bachmann PA, Plotkin SA.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271300
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Secretion of human serum albumin from Bacillus subtilis. by Saunders CW, Schmidt BJ, Mallonee RL, Guyer MS.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212327
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Site-specific de-N-glycosylation of diglycosylated ovalbumin in hen oviduct by endogenous peptide: N-glycanase as a quality control system for newly synthesized proteins. by Suzuki T, Kitajima K, Emori Y, Inoue Y, Inoue S.; 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21034
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Spatiotemporal expression patterns of chicken ovalbumin upstream promotertranscription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon. by Qiu Y, Cooney AJ, Kuratani S, DeMayo FJ, Tsai SY, Tsai MJ.; 1994 May 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43803
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Specific endonucleolytic cleavages of mouse albumin mRNA and their modulation during liver development. by Tharun S, Sirdeshmukh R.; 1995 Feb 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306732
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Splicing mutation in human hereditary analbuminemia. by Ruffner DE, Dugaiczyk A.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279941
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Structural basis of albumin --thyroxine interactions and familial dysalbuminemic hyperthyroxinemia. by Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry S.; 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164465
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Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin. by Takahashi N, Takahashi Y, Putnam FW.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299304
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Studies of the role of the propeptides of the Arabidopsis thaliana 2S albumin. by D'Hondt K, Van Damme J, Van Den Bossche C, Leejeerajumnean S, De Rycke R, Derksen J, Vandekerckhove J, Krebbers E.; 1993 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158796
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Substances interfering with direct detection of Mycobacterium tuberculosis in clinical specimens by PCR: effects of bovine serum albumin. by Forbes BA, Hicks KE.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229202
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Suppression of albumin enhancer activity by H-ras and AP-1 in hepatocyte cell lines. by Hu J, Isom HC.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=358512
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Surface receptors for serum albumin in group C and G streptococci show three different types of albumin specificity. by Wideback K, Kronvall G.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347870
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Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy. by Gorevic PD, Prelli FC, Wright J, Pras M, Frangione B.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303756
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The 28 --111 disulfide bond constrains the [alpha]-lactalbumin molten globule and weakens its cooperativity of folding. by Luo Y, Baldwin RL.; 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18025
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The mouse albumin enhancer contains a negative regulatory element that interacts with a novel DNA-binding protein. by Herbst RS, Boczko EM, Darnell JE Jr, Babiss LE.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360900
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The principle of delivery of T cell epitopes to antigen-presenting cells applied to peptides from influenza virus, ovalbumin, and hen egg lysozyme: Implications for peptide vaccination. by Rasmussen IB, Lunde E, Michaelsen TE, Bogen B, Sandlie I.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56955
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The rat albumin gene promoter is appropriately regulated in transient but not in stable transfections. by Berland R, Chasin LA.; 1988 Dec 23; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339082
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The same substitution, glutamic acid----lysine at position 501, occurs in three alloalbumins of Asiatic origin: albumins Vancouver, Birmingham, and Adana. by Huss K, Madison J, Ishioka N, Takahashi N, Arai K, Putnam FW.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282043
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The vacuolar targeting signal of the 2S albumin from Brazil nut resides at the C terminus and involves the C-terminal propeptide as an essential element. by Saalbach G, Rosso M, Schumann U.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158024
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Thyroxine transport and distribution in Nagase analbuminemic rats. by Mendel CM, Cavalieri RR, Gavin LA, Pettersson T, Inoue M.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303654
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Transport of nitrated albumin across continuous vascular endothelium. by Predescu D, Predescu S, Malik AB.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129800
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Tse-2: a trans-dominant extinguisher of albumin gene expression in hepatoma hybrid cells. by Chin AC, Fournier RE.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362434
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Tumor necrosis factor-alpha inhibits albumin gene expression in a murine model of cachexia. by Brenner DA, Buck M, Feitelberg SP, Chojkier M.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296412
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Uptake of proteins and degradation of human serum albumin by Plasmodium falciparum -- infected human erythrocytes. by El Tahir A, Malhotra P, Chauhan VS.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161787
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Use of 125I- and 51Cr-Labeled Albumin for the Measure ment of Gastrointestinal and Total Albumin Catabolism. by Kerr RM, Bois JJ, Holt PR.; 1967 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292957
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Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice. by Stacey A, Schnieke A, McWhir J, Cooper J, Colman A, Melton DW.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=358456
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Use of the KlADH4 Promoter for Ethanol-Dependent Production of Recombinant Human Serum Albumin in Kluyveromyces lactis. by Saliola M, Mazzoni C, Solimando N, Crisa A, Falcone C, Jung G, Fleer R.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90982
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with albumin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “albumin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for albumin (hyperlinks lead to article summaries): •
A biochromatographic framework to evaluate the calcium effect on the antihypertensive molecule-human serum albumin binding. Author(s): Andre C, Thomassin M, Guyon C, Truong TT, Guillaume YC. Source: Journal of Pharmaceutical and Biomedical Analysis. 2003 June 1; 32(2): 217-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763531
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A different view on human albumin. Author(s): Nohe B, Dieterich HJ. Source: Cardiovascular Research. 2003 June 1; 58(3): 721-2; Author Reply 723-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798447
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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A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Author(s): Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Fichtner I, Kratz F. Source: Cancer Research. 2003 July 15; 63(14): 4062-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874007
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A new endotoxin adsorption device in Gram-negative sepsis: use of immobilized albumin with the MATISSE adsorber. Author(s): Staubach KH, Boehme M, Zimmermann M, Otto V. Source: Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2003 August; 29(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877899
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A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings. Author(s): Damascelli B, Patelli GL, Lanocita R, Di Tolla G, Frigerio LF, Marchiano A, Garbagnati F, Spreafico C, Ticha V, Gladin CR, Palazzi M, Crippa F, Oldini C, Calo S, Bonaccorsi A, Mattavelli F, Costa L, Mariani L, Cantu G. Source: Ajr. American Journal of Roentgenology. 2003 July; 181(1): 253-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818869
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A rapid, simple measurement of human albumin in whole blood using a fluorescence immunoassay (I). Author(s): Choi S, Choi EY, Kim DJ, Kim JH, Kim TS, Oh SW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004 January; 339(1-2): 147-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687905
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A synergistic effect of albumin and fibrinogen on immunoglobulin-induced red blood cell aggregation. Author(s): Ben-Ami R, Barshtein G, Mardi T, Deutch V, Elkayam O, Yedgar S, Berliner S. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 December; 285(6): H2663-9. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869382
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Albumin adducts of naphthalene metabolites as biomarkers of exposure to polycyclic aromatic hydrocarbons. Author(s): Waidyanatha S, Zheng Y, Serdar B, Rappaport SM. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2004 January; 13(1): 117-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744742
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Albumin adsorption on alkanethiols self-assembled monolayers on gold electrodes studied by chronopotentiometry. Author(s): Martins MC, Fonseca C, Barbosa MA, Ratner BD. Source: Biomaterials. 2003 September; 24(21): 3697-706. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818541
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Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to vascular endothelium. Author(s): Lang JD Jr, Figueroa M, Chumley P, Aslan M, Hurt J, Tarpey MM, Alvarez B, Radi R, Freeman BA. Source: Anesthesiology. 2004 January; 100(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695724
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Albumin dilution as a cause of hemolysis during plasmapheresis. Author(s): Forte FJ, Caravone D, Coyne MJ. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 January 15; 52(2): 207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879552
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Albumin endocytosis in endothelial cells induces TGF-beta receptor II signaling. Author(s): Siddiqui SS, Siddiqui ZK, Malik AB. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2004 May; 286(5): L1016-26. Epub 2004 January 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729511
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Albumin in vaginal fluid is a marker of infection in early pregnancy. Author(s): Vogel I, Thorsen P, Flyvbjerg A, Gronbaek H. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 December; 83(3): 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14643045
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Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury. Author(s): Quinlan GJ, Mumby S, Martin GS, Bernard GR, Gutteridge JM, Evans TW. Source: Critical Care Medicine. 2004 March; 32(3): 755-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15090958
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Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site. Author(s): Raymond WW, Ruggles SW, Craik CS, Caughey GH. Source: The Journal of Biological Chemistry. 2003 September 5; 278(36): 34517-24. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815038
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Albumin-adjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Author(s): Slomp J, van der Voort PH, Gerritsen RT, Berk JA, Bakker AJ. Source: Critical Care Medicine. 2003 May; 31(5): 1389-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771607
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Albumin-based dialysis as an effective treatment for severe traumatic hepatic necrosis. Author(s): Ben-Abraham R, Szold O, Nimrod A, Sorkine P. Source: Isr Med Assoc J. 2003 June; 5(6): 455-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841026
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Allergy to sesame in humans is associated primarily with IgE antibody to a 14 kDa 2S albumin precursor. Author(s): Wolff N, Cogan U, Admon A, Dalal I, Katz Y, Hodos N, Karin N, Yannai S. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2003 August; 41(8): 1165-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842185
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Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients. Author(s): Hadjadj S, Gallois Y, Alhenc-Gelas F, Chatellier G, Marre M, Genes N, Lievre M, Mann J, Menard J, Vasmant D; DIABHYCAR Study Group. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 677-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873298
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Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients. Author(s): Pecis M, Azevedo MJ, Moraes RS, Ferlin EL, Gross JL. Source: Diabetes Care. 2000 July; 23(7): 989-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895852
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Behavior of various mammalian albumins towards bilirubin binding and photochemical properties of different bilirubin-albumin complexes. Author(s): Tayyab S, Khan NJ, Khan MA, Kumar Y. Source: International Journal of Biological Macromolecules. 2003 January 15; 31(4-5): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568927
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Beneficial effect of albumin therapy attributable to alpha1-acid glycoprotein? Author(s): Muchitsch EM, Schwarz HP. Source: Stroke; a Journal of Cerebral Circulation. 2003 January; 34(1): 4-5; Author Reply 4-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511738
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Beneficial effects of human serum albumin on stability and functionality of alginate microcapsules fabricated in different ways. Author(s): Schneider S, Feilen P, Cramer H, Hillgartner M, Brunnenmeier F, Zimmermann H, Weber MM, Zimmermann U. Source: Journal of Microencapsulation. 2003 September-October; 20(5): 627-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909546
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Beyond expansion: structural studies on the transport roles of human serum albumin. Author(s): Curry S. Source: Vox Sanguinis. 2002 August; 83 Suppl 1: 315-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617161
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Bilirubin binding properties of pigeon serum albumin and its comparison with human serum albumin. Author(s): Khan MA, Kumar Y, Tayyab S. Source: International Journal of Biological Macromolecules. 2002 June 18; 30(3-4): 171-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063119
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Binding and relaxometric properties of heme complexes with cyanogen bromide fragments of human serum albumin. Author(s): Monzani E, Curto M, Galliano M, Minchiotti L, Aime S, Baroni S, Fasano M, Amoresano A, Salzano AM, Pucci P, Casella L. Source: Biophysical Journal. 2002 October; 83(4): 2248-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12324442
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Binding of Amadori glucose-modified albumin by the monocytic cell line MonoMac 6 activates protein kinase C epsilon protein tyrosine kinases and the transcription factors AP-1 and NF-kappaB. Author(s): Salazar R, Brandt R, Krantz S. Source: Glycoconjugate Journal. 2001 October; 18(10): 769-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441666
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Binding of bilirubin with albumin-coupled liposomes: implications in the treatment of jaundice. Author(s): Masood AK, Faisal SM, Mushahid MK, Nadeem A, Siddiqui MU, Owais M. Source: Biochimica Et Biophysica Acta. 2002 August 19; 1564(1): 219-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101016
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Binding of fatty acids facilitates oxidation of cysteine-34 and converts copperalbumin complexes from antioxidants to prooxidants. Author(s): Gryzunov YA, Arroyo A, Vigne JL, Zhao Q, Tyurin VA, Hubel CA, Gandley RE, Vladimirov YA, Taylor RN, Kagan VE. Source: Archives of Biochemistry and Biophysics. 2003 May 1; 413(1): 53-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706341
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Binding of quercetin with human serum albumin: a critical spectroscopic study. Author(s): Sengupta B, Sengupta PK. Source: Biopolymers. 2003; 72(6): 427-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587065
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Binding studies on aluminum(III)-albumin interaction. Author(s): Zatta P, Dalla Via L, Di Noto V. Source: Archives of Biochemistry and Biophysics. 2003 September 1; 417(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921780
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BioGlue: albumin/glutaraldehyde sealant in cardiac surgery. Author(s): Chao HH, Torchiana DF. Source: Journal of Cardiac Surgery. 2003 November-December; 18(6): 500-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992099
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Biophysical characterization of albumin preparations from blood serum of healthy donors and patients with renal diseases. Part I: spectrofluorometric analysis. Author(s): Parkhomenko TV, Klicenko OA, Shavlovski MM, Kuznetsova IM, Uversky VN, Turoverov KK. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 July; 8(7): Br261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118188
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Biophysical characterization of albumin preparations from blood serum of healthy donors and patients with renal diseases. Part II: evidence for the enhancement of the haptoglobin. Level at the pathological conditions. Author(s): Parkhomenko TV, Klicenko OA, Shavlovski MM, Poletaev AI, Kuznetsova IM, Uversky VN, Turoverov KK. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 July; 8(7): Br266-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118189
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Blood loss in infants and children for open heart operations: albumin 5% versus fresh-frozen plasma in the prime. Author(s): Oliver WC Jr, Beynen FM, Nuttall GA, Schroeder DR, Ereth MH, Dearani JA, Puga FJ. Source: The Annals of Thoracic Surgery. 2003 May; 75(5): 1506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12735570
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Botulinum toxin and human serum albumin. Author(s): Malhotra R, Huilgol SC, Selva D. Source: Archives of Ophthalmology. 2003 November; 121(11): 1661; Discussion 1661-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609937
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Bovine serum albumin and insulin-dependent diabetes mellitus; is cow's milk still a possible toxicological causative agent of diabetes? Author(s): Persaud DR, Barranco-Mendoza A. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2004 May; 42(5): 707-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046815
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Bovine serum albumin modified the intracellular distribution and improved the antiviral activity of an oligonucleotide. Author(s): Arnedo A, Irache JM, Gonzalez Gaitano G, Valganon M, Espuelas S. Source: Journal of Drug Targeting. 2003 May; 11(4): 197-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578106
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Bovine-serum-albumin-containing receptor phase better predicts transdermal absorption parameters for lipophilic compounds. Author(s): Cross SE, Anissimov YG, Magnusson BM, Roberts MS. Source: The Journal of Investigative Dermatology. 2003 April; 120(4): 589-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648221
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Breast milk activity during early lactation following maternal 99Tcm macroaggregated albumin lung perfusion scan. Author(s): McCauley E, Mackie A. Source: The British Journal of Radiology. 2002 May; 75(893): 464-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036842
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Characterization of an anti-human ovarian carcinomaxanti-human CD3 bispecific single-chain antibody with an albumin-original interlinker. Author(s): Fang M, Zhao R, Yang Z, Zhang Z, Li H, Zhang XT, Lin Q, Huang HL. Source: Gynecologic Oncology. 2004 January; 92(1): 135-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751149
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Characterization of FITC-albumin encapsulated poly(DL-lactide-co-glycolide) microspheres and its release characteristics. Author(s): Sun SW, Jeong YI, Jung SW, Kim SH. Source: Journal of Microencapsulation. 2003 July-August; 20(4): 479-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851048
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Characterization of recombinant cat albumin. Author(s): Reininger R, Swoboda I, Bohle B, Hauswirth AW, Valent P, Rumpold H, Valenta R, Spitzauer S. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 December; 33(12): 1695-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656357
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Cholesterol and serum albumin levels as predictors of cross infection, death, and length of hospital stay. Author(s): Delgado-Rodriguez M, Medina-Cuadros M, Gomez-Ortega A, MartinezGallego G, Mariscal-Ortiz M, Martinez-Gonzalez MA, Sillero-Arenas M. Source: Archives of Surgery (Chicago, Ill. : 1960). 2002 July; 137(7): 805-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093337
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Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. Author(s): Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, KraghHansen U, Otagiri M. Source: Aaps Pharmscitech. 2000 May 14; 1(2): E12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727845
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Clinical assessment of hepatic functional reserve using 99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases--validation of the use of SPECT and a new indicator. Author(s): Onodera Y, Takahashi K, Togashi T, Sugai Y, Tamaki N, Miyasaka K. Source: Ann Nucl Med. 2003 May; 17(3): 181-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846539
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Clinical significance of 99mTc-DTPA-galactosyl human serum albumin liver scintigraphy in follow-up patients with biliary atresia. Author(s): Ishii T, Nio M, Shimaoka S, Sano N, Sasaki H, Kimura D, Hayashi Y, Ohi R. Source: Journal of Pediatric Surgery. 2003 October; 38(10): 1486-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14577072
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Closure of bronchopleural fistulas using albumin-glutaraldehyde tissue adhesive. Author(s): Lin J, Iannettoni MD. Source: The Annals of Thoracic Surgery. 2004 January; 77(1): 326-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726093
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Colloidal effect of albumin on the placental lactogen and chorionic gonadotrophin releases from human term placental explants. Author(s): Lambot N, Lebrun P, Cirelli N, Vanbellinghen AM, Delogne-Desnoeck J, Graff G, Meuris S. Source: Biochemical and Biophysical Research Communications. 2004 March 5; 315(2): 342-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766213
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Comparative study of rabbit pyrogen test and human whole blood assay on human serum albumin. Author(s): Spreitzer I, Fischer M, Hartzsch K, Luderitz-Puchel U, Montag T. Source: Altex. 2002; 19 Suppl 1: 73-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12096333
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Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis. Author(s): Dixon H, Hawkins K, Stephenson T. Source: European Journal of Pediatrics. 1999 May; 158(5): 414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333127
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Comparison of coasting and intravenous albumin in the prevention of ovarian hyperstimulation syndrome. Author(s): Chen CD, Chao KH, Yang JH, Chen SU, Ho HN, Yang YS. Source: Fertility and Sterility. 2003 July; 80(1): 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849806
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Comparison of ischemia-modified albumin levels in patients undergoing percutaneous coronary intervention for unstable angina pectoris with versus without coronary collaterals. Author(s): Garrido IP, Roy D, Calvino R, Vazquez-Rodriguez JM, Aldama G, CosinSales J, Quiles J, Gaze DC, Kaski JC. Source: The American Journal of Cardiology. 2004 January 1; 93(1): 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697474
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Compatibility in vitro of albumin-heme (O(2) carrier) with blood cell components. Author(s): Huang Y, Komatsu T, Nakagawa A, Tsuchida E, Kobayashi S. Source: Journal of Biomedical Materials Research. 2003 August 1; 66A(2): 292-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888999
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Coordinated increase in albumin, fibrinogen, and muscle protein synthesis during hemodialysis: role of cytokines. Author(s): Raj DS, Dominic EA, Wolfe R, Shah VO, Bankhurst A, Zager PG, Ferrando A. Source: American Journal of Physiology. Endocrinology and Metabolism. 2004 April; 286(4): E658-64. Epub 2004 January 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722024
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Correcting albumin and urea before extubation. Author(s): Manzar S. Source: Critical Care Medicine. 2000 June; 28(6): 2181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890711
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Correlations of serum lipids, uric acid, and albumin among mothers, offspring, and siblings in Taipei, Taiwan. Author(s): Cheng HH, Yang SH, Chen C, Chiang MS. Source: Acta Paediatr Taiwan. 1999 July-August; 40(4): 225-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910618
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Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin. Author(s): Nishiguchi S, Shiomi S, Sasaki N, Iwata Y, Mikami S, Tanaka H, Kubo S, Ochi H. Source: Ann Nucl Med. 2000 June; 14(3): 231-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921491
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Cryoglobulin/albumin complexes in a patient with severe autoimmune syndrome. Author(s): Trendelenburg M, Lutz HU, Tissot JD, Moll S, Hoffmann T, Schifferli JA. Source: Scandinavian Journal of Rheumatology. 2003; 32(6): 367-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080269
Studies
99
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Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. Author(s): Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S. Source: Bmc Structural Biology [electronic Resource]. 2003 July 07; 3(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846933
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Decreased serum albumin levels in Taiwanese patients with schizophrenia. Author(s): Huang TL. Source: Psychiatry and Clinical Neurosciences. 2002 December; 56(6): 627-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485305
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Decreases in mean hemoglobin and serum albumin values in erythema nodosum leprosum and lepromatous leprosy. Author(s): Rea TH. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 2001 December; 69(4): 318-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035293
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Delayed post-ischemic albumin treatment neither improves nor worsens the outcome of transient focal cerebral ischemia in rats. Author(s): Belayev L, Khoutorova L, Belayev A, Zhang Y, Zhao W, Busto R, Ginsberg MD. Source: Brain Research. 2004 February 20; 998(2): 243-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751596
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Depletion of the highly abundant protein albumin from human plasma using the Gradiflow. Author(s): Rothemund DL, Locke VL, Liew A, Thomas TM, Wasinger V, Rylatt DB. Source: Proteomics. 2003 March; 3(3): 279-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627381
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Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan. Author(s): Sun CA, Wu DM, Wang LY, Chen CJ, You SL, Santella RM. Source: British Journal of Cancer. 2002 October 21; 87(9): 966-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12434285
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Determination of albumin in biological fluids by flow injection analysis using the peroxyoxalate chemiluminescent system in micellar medium. Author(s): Gamiz-Gracia L, Garcia-Campana AM, Ales Barrero F, Cuadros Rodriguez L. Source: Analytical and Bioanalytical Chemistry. 2003 September; 377(2): 281-6. Epub 2003 May 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768265
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Determination of ferric heme-human serum albumin by 1H NMR relaxometry. Author(s): Fasano M, Baroni S, Aime S, Mattu M, Ascenzi P. Source: Journal of Inorganic Biochemistry. 2003 May 1; 95(1): 64-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706543
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Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Author(s): Kim JG, Baggio LL, Bridon DP, Castaigne JP, Robitaille MF, Jette L, Benquet C, Drucker DJ. Source: Diabetes. 2003 March; 52(3): 751-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606517
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Development of a high-level expression system for deuterium-labeled human serum albumin. Author(s): Tomida M, Kimura M, Kuwata K, Hayashi T, Okano Y, Era S. Source: Japanese Journal of Physiology. 2003 February; 53(1): 65-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689360
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Dielectric behavior and atomic structure of serum albumin. Author(s): Oncley JL. Source: Biophysical Chemistry. 2003; 100(1-3): 151-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646361
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Difference in the relation between urinary albumin excretion and carotid intimamedia thickness in nondiabetic and type 2 diabetic subjects. Author(s): Diercks GF, Stroes ES, Van Boven AJ, Van Roon AM, Hillege HL, De Jong PE, Smit AJ, Gans RO, Crijns HJ, Rabelink TJ, Van Gilst WH. Source: Diabetes Care. 2002 May; 25(5): 936-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978696
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Differentiation between endotoxin and non-endotoxin pyrogens in human albumin solutions using an ex vivo whole blood culture assay. Author(s): Pool EJ, Johaar G, James S, Petersen I, Bouic P. Source: J Immunoassay. 1999 February-May; 20(1-2): 79-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10225516
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Direct quantification of human serum albumin in human blood serum without separation of gamma-globulin by the total internal reflected resonance light scattering of thorium-sodium dodecylbenzene sulfonate at water/tetrachloromethane interface. Author(s): Feng P, Huang CZ, Li YF. Source: Analytical Biochemistry. 2002 September 1; 308(1): 83-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234467
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Discrepancies in serum albumin measurements vary by dialysis modality. Author(s): Parikh C, Yalavarthy R, Gurevich A, Robinson A, Teitelbaum I. Source: Renal Failure. 2003 September; 25(5): 787-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575287
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Disturbed circadian rhythm of urinary albumin excretion in non-dipper type of essential hypertension. Author(s): Nishimura M, Uzu T, Fujii T, Kimura G. Source: American Journal of Nephrology. 2002 September-December; 22(5-6): 455-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381943
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Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion. Author(s): Carlstrom K, Karlsson R, Von Schoultz B. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2002; 62(5): 361-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387582
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Does giving albumin infusion in hypoalbuminaeimic children with oncological disease affect colloid osmotic pressure and outcome? Author(s): Gupta S, Tasker RC. Source: Archives of Disease in Childhood. 2002 May; 86(5): 380-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11970941
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Does high albumin gradient ascites accompany tuberculous peritonitis? Author(s): Gurbuz AK, Yazgan Y, Ozel MA, Cavuslu S, Altunay H, Yildirim S. Source: Journal of Clinical Gastroenterology. 2003 January; 36(1): 82-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488720
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Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass? Author(s): Onorati F, Santarpino G, Renzulli A, De Feo M, De Santo LS, Della Corte A, Galdieri N, Cotrufo M. Source: Int J Artif Organs. 2003 March; 26(3): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12703887
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Durability of the binding inhibition of albumin coating on tympanostomy tubes. Author(s): Kinnari TJ, Salonen EM, Jero J. Source: International Journal of Pediatric Otorhinolaryngology. 2003 February; 67(2): 157-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623152
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Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings. Author(s): Celik I, Duda D, Stinner B, Kimura K, Gajek H, Lorenz W. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 October; 52(10): 408-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520516
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Effect of albumin fusion on the biodistribution of interleukin-2. Author(s): Yao Z, Dai W, Perry J, Brechbiel MW, Sung C. Source: Cancer Immunology, Immunotherapy : Cii. 2004 May; 53(5): 404-10. Epub 2003 November 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624312
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Effect of charge on interstitial distribution of albumin in rat dermis in vitro. Author(s): Wiig H, Kolmannskog O, Tenstad O, Bert JL. Source: The Journal of Physiology. 2003 July 15; 550(Pt 2): 505-14. Epub 2003 May 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766239
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Effect of direct-current cardioversion on ischemia-modified albumin levels in patients with atrial fibrillation. Author(s): Roy D, Quiles J, Sinha M, Aldama G, Gaze D, Kaski JC. Source: The American Journal of Cardiology. 2004 February 1; 93(3): 366-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759394
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Effect of human albumin administration on clinical outcome and hospital cost in patients with subarachnoid hemorrhage. Author(s): Suarez JI, Shannon L, Zaidat OO, Suri MF, Singh G, Lynch G, Selman WR. Source: Journal of Neurosurgery. 2004 April; 100(4): 585-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070109
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Effect of ibuprofen on bilirubin-albumin binding. Author(s): Ahlfors CE. Source: The Journal of Pediatrics. 2004 March; 144(3): 386-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001951
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Effect of the cytoskeletal fixation agent phalloidin on transcapillary albumin transport and interstitial fluid pressure in anaphylaxis in the wistar rat. Author(s): Bronstad A, Reith A, Berg A, Reed RK. Source: Microcirculation (New York, N.Y. : 1994). 2002 July; 9(3): 197-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12080417
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Effect of total parenteral nutrition products on enzymatic measurements of glycated albumin. Author(s): Tanabe H, Tsuji N, Endoh T, Nasu S, Koyanagi Y, Koshida S, Tamura K, Yagihasghi A, Watanabe N. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 July 1; 333(1): 103-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809745
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Effects of dialyzer membrane on serum albumin levels in patients receiving hemodialysis. Author(s): Rault RM. Source: Int J Artif Organs. 2003 November; 26(11): 1002-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708829
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Effects of feeding on albumin synthesis in hypoalbuminemic hemodialysis patients. Author(s): Louden JD, Bartlett K, Reaich D, Edson R, Alexander C, Goodship TH. Source: Kidney International. 2002 July; 62(1): 266-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081587
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Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). Author(s): Marre M, Lievre M, Chatellier G, Mann JF, Passa P, Menard J; DIABHYCAR Study Investigators. Source: Bmj (Clinical Research Ed.). 2004 February 28; 328(7438): 495. Epub 2004 Feb 11. Erratum In: Bmj. 2004 March 20; 328(7441): 686. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14960504
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Effects of oral contraceptives on total serum proteins, albumin, globulins and cholesterol levels in Ibadan, Nigeria. Author(s): Obisesan KA, Adenaike FA, Okunlola MA, Adenaike AA. Source: West Afr J Med. 2002 July-September; 21(3): 197-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744566
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Effects of organic and inorganic polyamine cations on the structure of human serum albumin. Author(s): Ouameur AA, Mangier E, Diamantoglou S, Rouillon R, Carpentier R, TajmirRiahi HA. Source: Biopolymers. 2004 March; 73(4): 503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991668
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Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells. Author(s): Lee EM, Pollock CA, Drumm K, Barden JA, Poronnik P. Source: American Journal of Physiology. Renal Physiology. 2003 October; 285(4): F74857. Epub 2003 June 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799307
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Effects of the angiotensin II type 1 receptor antagonist candesartan, compared with angiotensin-converting enzyme inhibitors, on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy. Author(s): Sato A, Tabata M, Hayashi K, Saruta T. Source: Clinical and Experimental Nephrology. 2003 September; 7(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586718
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Enhanced detection of malignant glioma xenograft by fluorescein-human serum albumin conjugate. Author(s): Ichioka T, Miyatake S, Asai N, Kajimoto Y, Nakagawa T, Hayashi H, Kuroiwa T. Source: Journal of Neuro-Oncology. 2004 March-April; 67(1-2): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072447
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Evaluation of persistence of ductus venosus with tc-99m DTPA galactosyl human serum albumin liver scintigraphy and I-123 iodoamphetamine per-rectal portal scintigraphy. Author(s): Kira T, Ikeda S, Sera Y, Tomiguchi S, Takahashi M, Uchino T, Endo F. Source: Ann Nucl Med. 2000 June; 14(3): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921487
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Ex vivo myeloid differentiation of cord blood CD34+ cells: comparison of four serumfree media containing bovine or human albumin. Author(s): De Bruyn C, Delforge A, Bron D. Source: Cytotherapy. 2003; 5(2): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745577
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Experience with an albumin-glutaraldehyde tissue adhesive in sealing air leaks after bullectomy. Author(s): Potaris K, Mihos P, Gakidis I. Source: Heart Surg Forum. 2003; 6(5): 429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14721826
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Extraction of uraemic toxins with activated carbon restores the functional properties of albumin. Author(s): Sarnatskaya VV, Lindup WE, Ivanov AI, Yushko LA, Tjia J, Maslenny VN, Gurina NM, Nikolaev VG. Source: Nephron. Physiology [electronic Resource]. 2003; 95(1): P10-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520007
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Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease. Author(s): Kaysen GA, Don BR. Source: Kidney International. Supplement. 2003 May; (84): S94-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694319
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Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant albumin (R218P) shows an apparent discrepancy between serum concentration and affinity for thyroxine. Author(s): Pannain S, Feldman M, Eiholzer U, Weiss RE, Scherberg NH, Refetoff S. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 August; 85(8): 2786-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10946882
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Familial dysalbuminemic hyperthyroxinemia: a rare example of albumin polymorphism and its rapid molecular diagnosis. Author(s): AvRuskin TW, Juan CS, Weiss RE. Source: J Pediatr Endocrinol Metab. 2002 June; 15(6): 801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099390
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Fatty acids carried on albumin modulate proximal tubular cell fibronectin production: a role for protein kinase C. Author(s): Arici M, Brown J, Williams M, Harris KP, Walls J, Brunskill NJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 October; 17(10): 1751-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12270980
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Female sex selection using clomiphene citrate and albumin separation of human sperm. Author(s): Silverman AY, Stephens SR, Drouin MT, Zack RG, Osborne J, Ericsson SA. Source: Human Reproduction (Oxford, England). 2002 May; 17(5): 1254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11980748
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Femtosecond studies of protein-ligand hydrophobic binding and dynamics: human serum albumin. Author(s): Zhong D, Douhal A, Zewail AH. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 19; 97(26): 14056-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106379
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Fetal growth and urinary albumin excretion among middle-aged Danes. Author(s): Johnsen SP, Sorensen HT, Thulstrup AM, Norgard B, Engberg M, Lauritzen T. Source: Scandinavian Journal of Urology and Nephrology. 2001 September; 35(4): 314-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11676359
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Fibrinogen-conjugated albumin polymers and their interaction with platelets under flow conditions. Author(s): Takeoka S, Teramura Y, Okamura Y, Handa M, Ikeda Y, Tsuchida E. Source: Biomacromolecules. 2001 Winter; 2(4): 1192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777392
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Five recombinant fragments of human serum albumin-tools for the characterization of the warfarin binding site. Author(s): Dockal M, Chang M, Carter DC, Ruker F. Source: Protein Science : a Publication of the Protein Society. 2000 August; 9(8): 1455-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10975567
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Flunitrazepam, a 7-nitro-1,4-benzodiazepine that is unable to bind to the indolebenzodiazepine site of human serum albumin. Author(s): Chuang VT, Otagiri M. Source: Biochimica Et Biophysica Acta. 2001 April 7; 1546(2): 337-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295439
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Fluorescence properties of albumin blue 633 and 670 in plasma and whole blood. Author(s): Abugo OO, Herman P, Lakowicz JR. Source: Journal of Biomedical Optics. 2001 July; 6(3): 359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11516328
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Fluorometric and mass spectrometric analysis of nonenzymatic glycosylated albumin. Author(s): Zoellner H, Hou JY, Hochgrebe T, Poljak A, Duncan MW, Golding J, Henderson T, Lynch G. Source: Biochemical and Biophysical Research Communications. 2001 June 1; 284(1): 839. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374874
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Follow-up study of auditory brainstem responses in infants with high unbound bilirubin levels treated with albumin infusion therapy. Author(s): Hosono S, Ohno T, Kimoto H, Nagoshi R, Shimizu M, Nozawa M, Harada K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 October; 44(5): 488-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12225546
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Formation of nanomolar concentrations of S-nitroso-albumin in human plasma by nitric oxide. Author(s): Marley R, Patel RP, Orie N, Ceaser E, Darley-Usmar V, Moore K. Source: Free Radical Biology & Medicine. 2001 September 1; 31(5): 688-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522454
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Formation of polymerized mixed heparin/albumin surface layer and cellular adhesional responses. Author(s): Magoshi T, Matsuda T. Source: Biomacromolecules. 2002 September-October; 3(5): 976-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217043
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Free thyroxine solid-analog immunoassays. investigation of the albumin effect on the antibody binding to immobilized thyroxine-protein conjugates. Author(s): Zacharopoulou AD, Christofidis I, Kakabakos SE, Koupparis MA. Source: Journal of Immunoassay & Immunochemistry. 2002; 23(1): 95-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11848104
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Frontal gel chromatographic analysis of the interaction of a protein with selfassociating ligands: aberrant saturation in the binding of flavins to bovine serum albumin. Author(s): Sawada O, Ishida T, Horiike K. Source: Journal of Biochemistry. 2001 June; 129(6): 899-907. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388904
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Fructosamine assay using albumin extracted from serum. Author(s): Ohkawara E, Nohara Y, Kanno Y, Suzuki H, Matsumoto G, Kinoshita T, Watanabe M. Source: Biological & Pharmaceutical Bulletin. 2002 September; 25(9): 1121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230100
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Functional hepatic volume measured by technetium-99m-galactosyl-human serum albumin liver scintigraphy: comparison between hepatocyte volume and liver volume by computed tomography. Author(s): Kwon AH, Matsui Y, Ha-Kawa SK, Kamiyama Y. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232703
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Further evidence of hepatic transdifferentiation in hepatoid adenocarcinomas of the stomach: quantitative analysis of mRNA for albumin and hepatocyte nuclear factor4alpha. Author(s): Yano T, Kishimoto T, Tomaru U, Kawarada Y, Kato H, Yoshiki T, Ishikura H. Source: Pathology. 2003 February; 35(1): 75-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12701690
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Gastrectomy does not influence the levels of aminotransferases, total protein and albumin in humans. Author(s): Beyan C, Beyan E, Kaptan K, Ifran A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2004 March; 10(3): Le1. Epub 2004 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976445
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Gender- and race-specific determination of albumin excretion rate using albumin-tocreatinine ratio in single, untimed urine specimens: the Coronary Artery Risk Development in Young Adults Study. Author(s): Jacobs DR Jr, Murtaugh MA, Steffes M, Yu X, Roseman J, Goetz FC. Source: American Journal of Epidemiology. 2002 June 15; 155(12): 1114-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048225
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Gene delivery by cationic liposome-DNA complexes containing transferrin or serum albumin. Author(s): Simoes S, Pires P, da Cruz MT, Duzgunes N, de Lima MC. Source: Methods Enzymol. 2003; 373: 369-83. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714416
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Genetic immunization with lung-targeting macroaggregated polyethyleneiminealbumin conjugates elicits combined systemic and mucosal immune responses. Author(s): Orson FM, Kinsey BM, Hua PJ, Bhogal BS, Densmore CL, Barry MA. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 June 15; 164(12): 6313-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10843685
Studies
109
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Genetic variants showing apparent hot-spots in the human serum albumin gene. Author(s): Galliano M, Kragh-Hansen U, Tarnoky AL, Chapman JC, Campagnoli M, Minchiotti L. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 November; 289(1-2): 45-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10556652
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Genomic expansion across the albumin gene family on human chromosome 4q is directional. Author(s): Nishio H, Hamdi HK, Dugaiczyk A. Source: Biological Chemistry. 1999 December; 380(12): 1431-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10661870
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Glial cell responses to lipids bound to albumin in serum and plasma. Author(s): Nadal A, Fuentes E, McNaughton PA. Source: Prog Brain Res. 2001; 132: 367-74. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11545003
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Gliclazide reduces the induction of human monocyte adhesion to endothelial cells by glycated albumin. Author(s): Desfaits AC, Serri O, Renier G. Source: Diabetes, Obesity & Metabolism. 1999 March; 1(2): 113-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220509
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Glomerular filtration rate, urinary albumin excretion rate, and blood pressure changes in normoalbuminuric normotensive type 1 diabetic patients: an 8-year follow-up study. Author(s): Caramori ML, Gross JL, Pecis M, de Azevedo MJ. Source: Diabetes Care. 1999 September; 22(9): 1512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480518
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Glucose and free radicals impair the antioxidant properties of serum albumin. Author(s): Bourdon E, Loreau N, Blache D. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 February; 13(2): 233-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973311
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Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C. Author(s): Hattori Y, Kakishita H, Akimoto K, Matsumura M, Kasai K. Source: Biochemical and Biophysical Research Communications. 2001 March 9; 281(4): 891-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11237743
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Glycation of human serum albumin by acylglucuronides of nonsteroidal antiinflammatory drugs of the series of phenylpropionates. Author(s): Georges H, Jarecki I, Netter P, Magdalou J, Lapicque F. Source: Life Sciences. 1999; 65(12): Pl151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10503951
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Growth hormone does not affect albumin synthesis in the critically ill. Author(s): Barle H, Gamrin L, Essen P, McNurlan MA, Garlick PJ, Wernerman J. Source: Intensive Care Medicine. 2001 May; 27(5): 836-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430539
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Hemoglobin-vesicles suspended in recombinant human serum albumin for resuscitation from hemorrhagic shock in anesthetized rats. Author(s): Sakai H, Masada Y, Horinouchi H, Yamamoto M, Ikeda E, Takeoka S, Kobayashi K, Tsuchida E. Source: Critical Care Medicine. 2004 February; 32(2): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14758176
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Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma. Author(s): Nakamura T, Ushiyama C, Suzuki Y, Shoji H, Shimada N, Koide H. Source: Asaio Journal (American Society for Artificial Internal Organs : 1992). 2002 MayJune; 48(3): 244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058997
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Hemostatic effects of polymerized albumin particles bearing rGPIa/IIa in thrombocytopenic mice. Author(s): Teramura Y, Okamura Y, Takeoka S, Tsuchiyama H, Narumi H, Kainoh M, Handa M, Ikeda Y, Tsuchida E. Source: Biochemical and Biophysical Research Communications. 2003 June 20; 306(1): 256-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788097
Studies
111
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Heterogeneity in the effect of albumin and other resuscitation fluids on intracellular oxygen free radical production. Author(s): Simpkins CO, Little D, Brenner A, Hill JA, Griswold JA. Source: The Journal of Trauma. 2004 March; 56(3): 548-58; Discussion 558-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128126
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High permeability of dialysis membranes: what is the limit of albumin loss? Author(s): Krieter DH, Canaud B. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 April; 18(4): 651-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637630
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High prevalence of immuno-unreactive intact albumin in urine of diabetic patients. Author(s): Comper WD, Osicka TM, Jerums G. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 February; 41(2): 336-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552494
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Higher urinary albumin excretion is associated with abnormal erythrocyte Na(+)/Li(+) countertransport (SLC) in non-modulating essential hypertensives and offspring of hypertensive parents. Author(s): Sanchez RA, Giannone C, Masnatta LD, Baglivo HP, Ramirez AJ. Source: Journal of Human Hypertension. 2002 March; 16 Suppl 1: S128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986910
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Homocysteine and cysteine - albumin binding in homocystinuria: assessment of cysteine status and implications for glutathione synthesis? Author(s): Hargreaves IP, Lee PJ, Briddon A. Source: Amino Acids. 2002; 22(2): 109-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395179
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Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial. Author(s): Vermeulen EG, Rauwerda JA, van den Berg M, de Jong SC, Schalkwijk C, Twisk JW, Stehouwer CD. Source: European Journal of Clinical Investigation. 2003 March; 33(3): 209-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641538
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How do fatty acids cause allosteric binding of drugs to human serum albumin? Author(s): Chuang VT, Otagiri M. Source: Pharmaceutical Research. 2002 October; 19(10): 1458-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425462
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HRT does not improve urinary albumin excretion in postmenopausal diabetic women. Author(s): Manning PJ, Sutherland WH, Allum AR, de Jong SA, Jones SD. Source: Diabetes Research and Clinical Practice. 2003 April; 60(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639763
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Human albumin administration in critically ill patients. Author(s): Ferguson ND, Stewart TE, Etchells EE. Source: Intensive Care Medicine. 1999 March; 25(3): 323-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10229170
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Human albumin enhances expression of vascular endothelial growth factor in cultured human luteinizing granulosa cells: importance in ovarian hyperstimulation syndrome. Author(s): Doldi N, Destefani A, Gessi A, Grossi D, Ferrari A. Source: Human Reproduction (Oxford, England). 1999 May; 14(5): 1157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10325253
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Human albumin synthesis is increased by an ultra-endurance trial. Author(s): Mischler I, Boirie Y, Gachon P, Pialoux V, Mounier R, Rousset P, Coudert J, Fellmann N. Source: Medicine and Science in Sports and Exercise. 2003 January; 35(1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544639
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Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase C alpha-mediated mechanism. Author(s): Miele C, Riboulet A, Maitan MA, Oriente F, Romano C, Formisano P, Giudicelli J, Beguinot F, Van Obberghen E. Source: The Journal of Biological Chemistry. 2003 November 28; 278(48): 47376-87. Epub 2003 September 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970360
Studies
113
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Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidantinduced neuronal death. Author(s): Gum ET, Swanson RA, Alano C, Liu J, Hong S, Weinstein PR, Panter SS. Source: Stroke; a Journal of Cerebral Circulation. 2004 February; 35(2): 590-5. Epub 2004 January 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726550
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Human serum albumin and its structural variants mediate cholesterol efflux from cultured endothelial cells. Author(s): Ha JS, Ha CE, Chao JT, Petersen CE, Theriault A, Bhagavan NV. Source: Biochimica Et Biophysica Acta. 2003 May 12; 1640(2-3): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729921
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Human serum albumin-polyethylenimine nanoparticles for gene delivery. Author(s): Rhaese S, von Briesen H, Rubsamen-Waigmann H, Kreuter J, Langer K. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2003 September 19; 92(1-2): 199-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499197
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Hyaluronic acid can successfully replace albumin as the sole macromolecule in a human embryo transfer medium. Author(s): Simon A, Safran A, Revel A, Aizenman E, Reubinoff B, Porat-Katz A, Lewin A, Laufer N. Source: Fertility and Sterility. 2003 June; 79(6): 1434-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798894
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Hypoglycemia in nondiabetic patients undergoing albumin dialysis by molecular adsorbent recirculating system. Author(s): Khoo AL, Tham LS, Lim GK, Lee KH. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 September; 9(9): 949-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942456
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Identification and characterisation of the IgE-binding proteins 2S albumin and conglutin gamma in almond (Prunus dulcis) seeds. Author(s): Poltronieri P, Cappello MS, Dohmae N, Conti A, Fortunato D, Pastorello EA, Ortolani C, Zacheo G. Source: International Archives of Allergy and Immunology. 2002 June; 128(2): 97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065909
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Identification of a new cross-link and unique histidine adduct from bovine serum albumin incubated with malondialdehyde. Author(s): Slatter DA, Avery NC, Bailey AJ. Source: The Journal of Biological Chemistry. 2004 January 2; 279(1): 61-9. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570889
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Improved oxygenation in acute lung injury: albumin gain or fluid loss? Author(s): Hatherill M, Dunkley R, Reynolds L, Argent A. Source: Critical Care Medicine. 2003 June; 31(6): 1886; Author Reply 1886-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794447
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In vitro and in vivo antitumor activity of methotrexate conjugated to human serum albumin in human cancer cells. Author(s): Wosikowski K, Biedermann E, Rattel B, Breiter N, Jank P, Loser R, Jansen G, Peters GJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 May; 9(5): 1917-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738750
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Increased levels of bovine serum albumin antibodies in patients with type 1 diabetes and celiac disease-related antibodies. Author(s): Rodriguez-Juan C, Sala-Silveira L, Perez-Blas M, Valeri AP, Aguilera N, Lopez-Santalla M, Fuertes A, Martin-Villa JM. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 August; 37(2): 132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883297
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Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. Author(s): Navarro JF, Mora C, Maca M, Garca J. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 July; 42(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830456
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Inhaled anesthetic binding sites in human serum albumin. Author(s): Eckenhoff RG, Petersen CE, Ha CE, Bhagavan NV. Source: The Journal of Biological Chemistry. 2000 September 29; 275(39): 30439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896670
Studies
115
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Interaction with leukocytes: phospholipid-stabilized versus albumin-shell microbubbles. Author(s): Takeuchi H, Ohmori K, Kondo I, Shinomiya K, Oshita A, Takagi Y, Yoshida J, Mizushige K, Kohno M. Source: Radiology. 2004 March; 230(3): 735-42. Epub 2004 January 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739305
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Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability. Author(s): Cho MH, Lee HS, Choe BH, Kwon SH, Chung KY, Koo JH, Ko CW. Source: American Journal of Nephrology. 2003 July-August; 23(4): 260-6. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840601
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Intermediate formation at lower urea concentration in 'B' isomer of human serum albumin: a case study using domain specific ligands. Author(s): Ahmad B, Khan MK, Haq SK, Khan RH. Source: Biochemical and Biophysical Research Communications. 2004 January 30; 314(1): 166-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715261
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Intervention strategies to prevent pathogenetic effects of glycated albumin. Author(s): Cohen MP. Source: Archives of Biochemistry and Biophysics. 2003 November 1; 419(1): 25-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568005
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Intramolecular complex formation of poly(N-isopropylacrylamide) with human serum albumin. Author(s): Matsudo T, Ogawa K, Kokufuta E. Source: Biomacromolecules. 2003 May-June; 4(3): 728-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741791
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Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection. Author(s): Martinez-Palones JM, Gil-Moreno A, Perez-Benavente MA, Roca I, Xercavins J. Source: Gynecologic Oncology. 2004 March; 92(3): 845-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984951
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Intratracheal albumin reduces interleukin-8 in tracheobronchial aspirates in piglets after meconium aspiration. Author(s): Tollofsrud PA, Medbo S, Solas AB, Robertson B, Speer CP, Seidenspinner S, Drevon CA, Saugstad OD. Source: Journal of Perinatal Medicine. 2004; 32(1): 78-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008393
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Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome. Author(s): Aboulghar M, Evers JH, Al-Inany H. Source: Cochrane Database Syst Rev. 2002; (2): Cd001302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076404
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Is serum albumin a marker of nutritional status in hemodialysis patients without evidence of inflammation? Author(s): Santos NS, Draibe SA, Kamimura MA, Canziani ME, Cendoroglo M, Junior AG, Cuppari L. Source: Artificial Organs. 2003 August; 27(8): 681-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911340
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Is the use of albumin of value in cirrhosis? The case not so in favour, or is there an alternative? Author(s): Burroughs AK. Source: Dig Liver Dis. 2003 September; 35(9): 664-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563191
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Is the use of albumin of value in the treatment of ascites in cirrhosis? The case in favour. Author(s): Laffi G, Gentilini P, Romanelli RG, La Villa G. Source: Dig Liver Dis. 2003 September; 35(9): 660-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563190
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Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Author(s): Sinha MK, Gaze DC, Tippins JR, Collinson PO, Kaski JC. Source: Circulation. 2003 May 20; 107(19): 2403-5. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742986
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Isolation and identification of heterogeneous nuclear ribonucleoproteins (hnRNP) from purified plasma membranes of human tumour cell lines as albumin-binding proteins. Author(s): Fritzsche T, Schnolzer M, Fiedler S, Weigand M, Wiessler M, Frei E. Source: Biochemical Pharmacology. 2004 February 15; 67(4): 655-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757165
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Kinetic analysis of covalent binding between N-acetyl-L-cysteine and albumin through the formation of mixed disulfides in human and rat serum in vitro. Author(s): Harada D, Naito S, Otagiri M. Source: Pharmaceutical Research. 2002 November; 19(11): 1648-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458670
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Kinetics of CO and O(2) binding to human serum albumin-heme hybrid. Author(s): Komatsu T, Matsukawa Y, Tsuchida E. Source: Bioconjugate Chemistry. 2000 November-December; 11(6): 772-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11087324
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Krypton-81m ventilation and technetium-99m macroaggregated albumin perfusion scintigraphy for detection of pulmonary embolism: the first experience in Taiwan. Author(s): Cherng SC, Yang SP, Wang YF, Jen TK, Huang WS, Lo AR. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 December; 63(12): 876-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195138
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Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes. Author(s): Otto C, Engelschalk C, Fraunberger P, Laubach E, Schwandt P. Source: Acta Diabetologica. 2001 December; 38(4): 153-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11855792
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Lack of association of fibrinogen, lipoprotein(a), and albumin excretion rate with low birthweight. Author(s): Bo S, Cavallo-Perin P, Scaglione L, Pagano G. Source: International Journal of Clinical & Laboratory Research. 2000; 30(4): 203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11289712
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Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy. Author(s): Myrup B, Rossing P, Jensen T, Parving HH, Holmer G, Gram J, Kluft C, Jespersen J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2001; 61(5): 34956. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11569481
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Laser ureteral anastomosis using intraluminal albumin stent in a porcine model. Author(s): Xie H, Shaffer BS, Prahl SA, Gregory KW. Source: Lasers in Surgery and Medicine. 2003; 32(4): 294-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12696097
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Laser welding for vascular anastomosis using albumin solder: an approach for MIDCAB. Author(s): Phillips AB, Ginsburg BY, Shin SJ, Soslow R, Ko W, Poppas DP. Source: Lasers in Surgery and Medicine. 1999; 24(4): 264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10327044
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Left ventricular mass assessed by electrocardiography and albumin excretion rate as a continuum in untreated essential hypertension. Author(s): Bulatov VA, Stenehjem A, Os I. Source: Journal of Hypertension. 2001 August; 19(8): 1473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518856
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Levels of alpha1 acid glycoprotein and ceruloplasmin predict future albumin levels in hemodialysis patients. Author(s): Kaysen GA, Dubin JA, Muller HG, Mitch WE, Levin NW; HEMO Group. Source: Kidney International. 2001 December; 60(6): 2360-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737611
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Levofloxacin elimination during albumin dialysis. Author(s): Bellmann R, Egger P, Pechlaner C, Feistritzer C, Vogel W, Joannidis M, Wiedermann CJ. Source: Int J Artif Organs. 2003 April; 26(4): 358-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757036
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Ligand binding to domain-3 of human serum albumin: a chemometric analysis. Author(s): Hajduk PJ, Mendoza R, Petros AM, Huth JR, Bures M, Fesik SW, Martin YC. Source: Journal of Computer-Aided Molecular Design. 2003 February-April; 17(2-4): 93102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13677478
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Linoleic acid, cis-epoxyoctadecenoic acids, and dihydroxyoctadecadienoic acids are toxic to Sf-21 cells in the absence of albumin. Author(s): Mitchell LA, Moran JH, Grant DF. Source: Toxicology Letters. 2002 February 7; 126(3): 187-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814707
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Longitudinal and cross-sectional effects of C-reactive protein, equilibrated normalized protein catabolic rate, and serum bicarbonate on creatinine and albumin levels in dialysis patients. Author(s): Kaysen GA, Greene T, Daugirdas JT, Kimmel PL, Schulman GW, Toto RD, Levin NW, Yan G; HEMO Study Group. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 December; 42(6): 1200-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655192
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Longitudinal study of specific antibodies to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in patients with TDI-induced asthma. Author(s): Park HS, Lee SK, Lee YM, Kim SS, Nahm DH. Source: Korean J Intern Med. 2002 December; 17(4): 249-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647640
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Longitudinal study of urinary albumin excretion in young diabetic patients--Wessex Diabetic Nephropathy Project. Author(s): Twyman S, Rowe D, Mansell P, Schapira D, Betts P, Leatherdale B; Wessex Diabetic Nephropathy Project. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 May; 18(5): 402-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472452
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Low albumin level in the emergency department: a potential independent predictor of delayed mortality in blunt trauma. Author(s): Yukl RL, Bar-Or D, Harris L, Shapiro H, Winkler JV. Source: The Journal of Emergency Medicine. 2003 July; 25(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865100
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Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin. Parametric and validation studies. Author(s): Johnston A, Uren E, Johnstone D, Wu J. Source: Biologicals : Journal of the International Association of Biological Standardization. 2003 September; 31(3): 213-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935811
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Low serum albumin in elderly continuous ambulatory peritoneal dialysis patients is attributable to high permeability of peritoneum. Author(s): Nakamoto H, Imai H, Kawanishi H, Nakamoto M, Minakuchi J, Kumon S, Watanabe S, Shiohira Y, Ishii T, Kawahara T, Suzuki H. Source: Adv Perit Dial. 2001; 17: 238-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510284
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Low serum albumin levels, confusion, and fecal incontinence: are these risk factors for pressure ulcers in mobility-impaired hospitalized adults? Author(s): Reed RL, Hepburn K, Adelson R, Center B, McKnight P. Source: Gerontology. 2003 July-August; 49(4): 255-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792162
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Low urinary albumin excretion in astronauts during space missions. Author(s): Cirillo M, De Santo NG, Heer M, Norsk P, Elmann-Larsen B, Bellini L, Stellato D, Drummer C. Source: Nephron. Physiology [electronic Resource]. 2003; 93(4): P102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759571
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Lower serum albumin levels in patients with mood disorders. Author(s): Huang TL. Source: Chang Gung Med J. 2002 August; 25(8): 509-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392362
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Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol. Author(s): Rink T, Heuser T, Fitz H, Schroth HJ, Weller E, Zippel HH. Source: Clinical Nuclear Medicine. 2001 April; 26(4): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11290886
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Maleimide-oligo(ethylene glycol) derivatives of camptothecin as albumin-binding prodrugs: synthesis and antitumor efficacy. Author(s): Warnecke A, Kratz F. Source: Bioconjugate Chemistry. 2003 March-April; 14(2): 377-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643748
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Management of a severe carbamazepine overdose using albumin-enhanced continuous venovenous hemodialysis. Author(s): Askenazi DJ, Goldstein SL, Chang IF, Elenberg E, Feig DI. Source: Pediatrics. 2004 February; 113(2): 406-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754959
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Measurement of hemoglobin and albumin adducts of naphthalene-1,2-oxide, 1,2naphthoquinone and 1,4-naphthoquinone after administration of naphthalene to F344 rats. Author(s): Waidyanatha S, Troester MA, Lindstrom AB, Rappaport SM. Source: Chemico-Biological Interactions. 2002 October 20; 141(3): 189-210. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385719
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Measurement of serum albumin by capillary zone electrophoresis, bromocresol green, bromocresol purple, and immunoassay methods. Author(s): Duly EB, Grimason S, Grimason P, Barnes G, Trinick TR. Source: Journal of Clinical Pathology. 2003 October; 56(10): 780-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514785
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Mechanical properties of coagulated albumin and failure mechanisms of liver repaired with the use of an argon-beam coagulator with albumin. Author(s): Moffitt TP, Baker DA, Kirkpatrick SJ, Prahl SA. Source: Journal of Biomedical Materials Research. 2002; 63(6): 722-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12418016
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Mechanism of binding of warfarin enantiomers to recombinant domains of human albumin. Author(s): Twine SM, Gore MG, Morton P, Fish BC, Lee AG, East JM. Source: Archives of Biochemistry and Biophysics. 2003 June 1; 414(1): 83-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745258
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Mechanism of bovine serum albumin aggregation during ultrafiltration. Author(s): Maruyama T, Katoh S, Nakajima M, Nabetani H. Source: Biotechnology and Bioengineering. 2001 October 20; 75(2): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11536147
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Mechanisms of drug photobinding to proteins: photobinding of suprofen to human serum albumin. Author(s): Moser J, Hye A, Lovell WW, Earl LK, Castell JV, Miranda MA. Source: Toxicology in Vitro : an International Journal Published in Association with Bibra. 2001 August-October; 15(4-5): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566558
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Melphalan monitoring during hyperthermic perfusion of isolated limb for melanoma: pharmacokinetic study and 99mTc-albumin microcolloid technique. Author(s): Cattel L, Buffa E, De Simone M, Cesana P, Novello S, Dosio F, Ceruti M. Source: Anticancer Res. 2001 May-June; 21(3C): 2243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501854
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Metabolic acidosis, core-peripheral temperature difference and blood pressure response to albumin infusion in hypotensive, very premature infants. Author(s): Dimitriou G, Greenough A, Mantagos J, Skinner S. Source: Journal of Perinatal Medicine. 2001; 29(5): 442-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11723846
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Methyl parathion interaction with human and bovine serum albumin. Author(s): Silva D, Cortez CM, Cunha-Bastos J, Louro SR. Source: Toxicology Letters. 2004 February 28; 147(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700528
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Milk or albumin? The history of proteinuria before Richard Bright. Author(s): Cameron JS. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 July; 18(7): 1281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808162
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Mishandling of copper by albumin: role in redox-cycling and oxidative stress in preeclampsia plasma. Author(s): Kagan VE, Tyurin VA, Borisenko GG, Fabisiak JP, Hubel CA, Ness RB, Gandley R, McLaughlin MK, Roberts JM. Source: Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy. 2001; 20(3): 221-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12044332
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Mode of action of methotrexate-albumin in a human T-cell leukemia line and activity against an MTX-resistant clone. Author(s): Weigand M, Hartung G, Roboz J, Sieger S, Wolf M, Sinn H, Schrenk HH, Wiessler M, Frei E. Source: Anti-Cancer Drug Design. 2001 August-October; 16(4-5): 227-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049481
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Modified serum albumin in the pathogenesis of glomerular diseases: a new hypothesis. Author(s): Kozhevnikov AD. Source: Archives of Internal Medicine. 2002 February 11; 162(3): 356-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11822932
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Modulation in the photosensitivity of albumin-bound bilirubin. Author(s): Tayyab S, Paliwal P, Khan MM. Source: International Journal of Biological Macromolecules. 2001 December 10; 29(4-5): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718823
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Molecular basis of sulindac competition with specific markers for the major binding sites on human serum albumin. Author(s): Russeva VN, Zhivkova ZD. Source: Arzneimittel-Forschung. 2003; 53(3): 174-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705172
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Multisite evaluation of a new dipstick for albumin, protein, and creatinine. Author(s): Wallace JF, Pugia MJ, Lott JA, Luke KE, Shihabi ZK, Sheehan M, Bucksa JM. Source: Journal of Clinical Laboratory Analysis. 2001; 15(5): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574949
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Neonatal respiratory distress syndrome as a function of gestational age and an assay for surfactant-to-albumin ratio. Author(s): McElrath TF, Colon I, Hecht J, Tanasijevic MJ, Norwitz ER. Source: Obstetrics and Gynecology. 2004 March; 103(3): 463-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990407
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Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Author(s): Doublier S, Salvidio G, Lupia E, Ruotsalainen V, Verzola D, Deferrari G, Camussi G. Source: Diabetes. 2003 April; 52(4): 1023-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663475
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Nephrotic urine prevents increased rat glomerular albumin permeability induced by serum from the same patient with idiopathic nephrotic syndrome. Author(s): Carraro M, Zennaro C, Candiano G, Musante L, Bruschi M, Ghiggeri GM, Artero M, Faccini L. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 April; 18(4): 689-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637636
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Neuroanesthesia and intensive care. Best evidence in anesthetic practice. Harm: albumin neither increases nor decreases mortality in critically ill patients. Author(s): Bryson GL. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 JuneJuly; 49(6): 620; Discussion 621. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12067877
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Nitric oxide synthesis and isoprostane production in subjects with type 1 diabetes and normal urinary albumin excretion. Author(s): O'Byrne S, Forte P, Roberts LJ 2nd, Morrow JD, Johnston A, Anggard E, Leslie RD, Benjamin N. Source: Diabetes. 2000 May; 49(5): 857-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10905497
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No direct link between albumin excretion rate and insulin resistance--a study in type 1 diabetes patients with mild nephropathy. Author(s): Svensson M, Eriksson JW. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 May; 34(5): 254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063639
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Non-linear production of benzene oxide-albumin adducts with human exposure to benzene. Author(s): Rappaport SM, Yeowell-O'Connell K, Smith MT, Dosemeci M, Hayes RB, Zhang L, Li G, Yin S, Rothman N. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 October 5; 778(1-2): 367-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376141
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Novel role for albumin in innate immunity: serum albumin inhibits the growth of Blastomyces dermatitidis yeast form in vitro. Author(s): Giles S, Czuprynski C. Source: Infection and Immunity. 2003 November; 71(11): 6648-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573690
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Nuclear export of phosphorylated C/EBPbeta mediates the inhibition of albumin expression by TNF-alpha. Author(s): Buck M, Zhang L, Halasz NA, Hunter T, Chojkier M. Source: The Embo Journal. 2001 December 3; 20(23): 6712-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726507
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Nucleation of calcium oxalate crystals by albumin: involvement in the prevention of stone formation. Author(s): Cerini C, Geider S, Dussol B, Hennequin C, Daudon M, Veesler S, Nitsche S, Boistelle R, Berthezene P, Dupuy P, Vazi A, Berland Y, Dagorn JC, Verdier JM. Source: Kidney International. 1999 May; 55(5): 1776-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10231440
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On the modulation of photoinduced fluorescence enhancement and conformational stability of albumin-bound bilirubin: effect of epsilon-NH(2) groups blocking and chloroform binding. Author(s): Khan MM, Tayyab S. Source: Biochimica Et Biophysica Acta. 2000 October 18; 1523(2-3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11042378
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Optic disk manifestation in diabetic eyes with low serum albumin: late fluorescein staining and high blood flow velocities in the optic disk. Author(s): Fujioka S, Karashima K, Nishikawa N, Saito Y. Source: Japanese Journal of Ophthalmology. 2004 January-February; 48(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767653
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Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Author(s): Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D. Source: International Journal of Pharmaceutics. 2003 May 12; 257(1-2): 169-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711172
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Optimum albumin concentration of supplementation fluid for double filtration plasmapheresis. Author(s): Mineshima M, Agishi T, Hasuo Y, Era K, Suzuki T, Teraoka S, Ota K. Source: Artificial Organs. 1992 October; 16(5): 510-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078302
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Oxidation affects the flow-induced aggregation of low density lipoprotein and its inhibition by albumin. Author(s): Talbot RM, del Rio JD, Leake DS, Weinberg PD. Source: Biochimica Et Biophysica Acta. 2003 October 20; 1634(1-2): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563410
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Oxidation of albumin is enhanced in the presence of uremic toxins. Author(s): Wratten ML, Sereni L, Tetta C. Source: Renal Failure. 2001 May-July; 23(3-4): 563-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499570
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Pharmaceutical strategies utilizing recombinant human serum albumin. Author(s): Chuang VT, Kragh-Hansen U, Otagiri M. Source: Pharmaceutical Research. 2002 May; 19(5): 569-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12069157
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Plasma disappearance of albumin and impact of capillary thickness in idiopathic dilated cardiomyopathy and after heart transplantation. Author(s): Galatius S, Bent-Hansen L, Wroblewski H, Sorensen VB, Norgaard T, Kastrup J. Source: Circulation. 2000 July 18; 102(3): 319-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899096
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Plasma volume expansion by albumin in cirrhosis. Relation to blood volume distribution, arterial compliance and severity of disease. Author(s): Brinch K, Moller S, Bendtsen F, Becker U, Henriksen JH. Source: Journal of Hepatology. 2003 July; 39(1): 24-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821040
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Polychlorinated biphenyls and organochlorine pesticides are eliminated from therapeutic Factor VIII and immunoglobulin concentrates and reduced in albumin by plasma fractionation. Author(s): Covaci A, Laub R, Di Giambattista M, Branckaert T, Hougardy V, Schepens P. Source: Vox Sanguinis. 2002 July; 83(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100385
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Practical aspects of the ligand-binding and enzymatic properties of human serum albumin. Author(s): Kragh-Hansen U, Chuang VT, Otagiri M. Source: Biological & Pharmaceutical Bulletin. 2002 June; 25(6): 695-704. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081132
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Predicting the decrease of conjugated bilirubin with extracorporeal albumin dialysis MARS using the predialysis molar ratio of conjugated bilirubin to albumin. Author(s): Lee KH, Wendon J, Lee M, Da Costa M, Lim SG, Tan KC. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 July; 8(7): 591-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089711
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Preliminary results with the use of an albumin-glutaraldehyde tissue adhesive in lung surgery. Author(s): Potaris K, Mihos P, Gakidis I. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 July; 9(7): Pi79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883462
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Preparation of a liposomal reagent and its use in an immunoassay for albumin. Author(s): Frost SJ. Source: Methods Enzymol. 2003; 373: 249-59. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714408
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Properties and human origin of two angiotensin-I-converting enzyme inhibitory peptides isolated from a tryptic hydrolysate of human serum albumin. Author(s): Nakagomi K, Ebisu H, Sadakane Y, Fujii N, Akizawa T, Tanimura T. Source: Biological & Pharmaceutical Bulletin. 2000 July; 23(7): 879-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919370
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Proteolysis and utilization of albumin by enrichment cultures of subgingival microbiota. Author(s): Wei GX, van der Hoeven JS, Smalley JW, Mikx FH, Fan MW. Source: Oral Microbiology and Immunology. 1999 December; 14(6): 348-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895689
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Quantification of intrahepatic non-uniform distributions for assessing impaired function of liver using 99Tcm-DTPA-galactosyl serum albumin liver SPECT scintigraphy. Author(s): Mitomo, Tsunoda T, Nakamura K, Kuwabara H. Source: Nuclear Medicine Communications. 2001 May; 22(5): 505-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388571
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Quantification of oxidative/nitrosative modification of CYS(34) in human serum albumin using a fluorescence-based SDS-PAGE assay. Author(s): Fabisiak JP, Sedlov A, Kagan VE. Source: Antioxidants & Redox Signalling. 2002 October; 4(5): 855-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470514
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Quantification of right-to-left shunt with (99m)Tc-labelled albumin macroaggregates and 100% oxygen in patients with hereditary haemorrhagic telangiectasia. Author(s): Mager JJ, Zanen P, Verzijlbergen F, Westermann CJ, Haitjema T, van Herk G, Lammers JW. Source: Clinical Science (London, England : 1979). 2002 February; 102(2): 127-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834132
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Quantitative comparison of alpha-fetoprotein and albumin mRNA levels in hepatocellular carcinoma/adenoma, non-tumor liver and blood: implications in cancer detection and monitoring. Author(s): Wong IH, Lau WY, Leung T, Johnson PJ. Source: Cancer Letters. 2000 August 11; 156(2): 141-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10880763
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Radioactivity in cervical mucus after intraperitoneal deposition of Tc-99m labelled albumin particles before and after sterilisation. Author(s): Wanggren K, Lundberg S, Lundberg HJ, Asard PE, Wramsby H. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 June 10; 108(2): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781412
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Rapid screening of small ligand affinity to human serum albumin by an optical biosensor. Author(s): Bertucci C, Cimitan S. Source: Journal of Pharmaceutical and Biomedical Analysis. 2003 August 8; 32(4-5): 70714. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899961
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Reactions of acrylamide with glutathione and serum albumin. Author(s): Tong GC, Cornwell WK, Means GE. Source: Toxicology Letters. 2004 March 1; 147(2): 127-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757316
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Relation of homocysteine and C-reactive protein to urinary albumin loss. Author(s): Seshadri N, Messerli AW, Acharya N, Pearce GL, Jacobsen DW, Pohl MA, Robinson K, Sprecher DL. Source: The American Journal of Cardiology. 2004 April 1; 93(7): 926-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15050501
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Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia. Author(s): Quiles J, Roy D, Gaze D, Garrido IP, Avanzas P, Sinha M, Kaski JC. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 322-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888145
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Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease. Author(s): Menon V, Wang X, Greene T, Beck GJ, Kusek JW, Marcovina SM, Levey AS, Sarnak MJ. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 July; 42(1): 44-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830455
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Release characteristics of cardiac biomarkers and ischemia-modified albumin as measured by the albumin cobalt-binding test after a marathon race. Author(s): Apple FS, Quist HE, Otto AP, Mathews WE, Murakami MM. Source: Clinical Chemistry. 2002 July; 48(7): 1097-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089181
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Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age. Author(s): Rzany B, Partscht K, Jung M, Kippes W, Mecking D, Baima B, Prudlo C, Pawelczyk B, Messmer EM, Schuhmann M, Sinkgraven R, Buchner L, Budinger L, Pfeiffer C, Sticherling M, Hertl M, Kaiser HW, Meurer M, Zillikens D, Messer G. Source: Archives of Dermatology. 2002 July; 138(7): 903-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12071817
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Risk stratification after acute myocardial infarction: role of neurohormones, inflammatory markers and albumin excretion rate. Author(s): Berton G, Palatini P. Source: Ital Heart J. 2003 May; 4(5): 295-304. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848085
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Role of salt sensitivity, blood pressure, and hyperinsulinemia in determining high upper normal levels of urinary albumin excretion in a healthy adult population. Author(s): Cubeddu LX, Hoffmann IS, Aponte LM, Nunez-Bogesits R, Medina-Suniaga H, Roa M, Garcia RS. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 May; 16(5 Pt 1): 343-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745194
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Saline has similar effect to albumin in critically ill patients. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2004 April 10; 328(7444): 852. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15073058
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Sera from patients with collapsing focal segmental glomerulosclerosis increase albumin permeability of isolated glomeruli. Author(s): McCarthy ET, Sharma M, Sharma R, Falk RJ, Jennette JC. Source: The Journal of Laboratory and Clinical Medicine. 2004 April; 143(4): 225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085081
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Serum albumin is a powerful predictor of survival among HIV-1-infected women. Author(s): Feldman JG, Gange SJ, Bacchetti P, Cohen M, Young M, Squires KE, Williams C, Goldwasser P, Anastos K. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 May 1; 33(1): 66-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792357
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Simultaneous determination of human serum albumin, gamma-globulin, and glucose in a phosphate buffer solution by near-infrared spectroscopy with moving window partial least-squares regression. Author(s): Kasemsumran S, Du YP, Murayama K, Huehne M, Ozaki Y. Source: The Analyst. 2003 December; 128(12): 1471-7. Epub 2003 November 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14737235
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Site specific 1:1 opioid:albumin conjugate with in vitro activity and long in vivo duration. Author(s): Holmes DL, Thibaudeau K, L'Archeveque B, Milner PG, Ezrin AM, Bridon DP. Source: Bioconjugate Chemistry. 2000 July-August; 11(4): 439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898563
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SPME-LC with UV detection to study delorazepam-serum albumin interactions. Author(s): Zambonin CG, Aresta A. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 July 31; 29(5): 895-900. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093523
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Structural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemia. Author(s): Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 May 27; 100(11): 6440-5. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743361
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Studies on the interaction between Ag(+) and human serum albumin. Author(s): Shen XC, Liang H, Guo JH, Song C, He XW, Yuan YZ. Source: Journal of Inorganic Biochemistry. 2003 June 1; 95(2-3): 124-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763656
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Subclinical hepatic encephalopathy: role of tryptophan binding to albumin and the competition with indole-3-acetic acid. Author(s): Greco AV, Mingrone G, Favuzzi A, Bertuzzi A, Gandolfi A, DeSmet R, Vanholder R, Gasbarrini G. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2000 July; 48(4): 274-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10916286
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Synthesis, comparative photosensitizing efficacy, human serum albumin (site II) binding ability, and intracellular localization characteristics of novel benzobacteriochlorins derived from vic-dihydroxybacteriochlorins. Author(s): Li G, Graham A, Chen Y, Dobhal MP, Morgan J, Zheng G, Kozyrev A, Oseroff A, Dougherty TJ, Pandey RK. Source: Journal of Medicinal Chemistry. 2003 December 4; 46(25): 5349-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640543
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Technetium-99m labelled macroaggregated albumin arterial catheter perfusion scintigraphy: prediction of gastrointestinal toxicity in hepatic arterial chemotherapy. Author(s): Pelosi E, Masaneo I, Clara R, Valetto MR, Bello M, Zanon C, Chiappino I, Grosso M, Mussa A, Bisi G. Source: European Journal of Nuclear Medicine. 2000 June; 27(6): 668-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10901453
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Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. Author(s): Uriz J, Gines P, Cardenas A, Sort P, Jimenez W, Salmeron JM, Bataller R, Mas A, Navasa M, Arroyo V, Rodes J. Source: Journal of Hepatology. 2000 July; 33(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10905585
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The binding of selected therapeutic drugs to human serum alpha-1 acid glycoprotein and to human serum albumin in vitro. Author(s): Bailey DN, Briggs JR. Source: Therapeutic Drug Monitoring. 2004 February; 26(1): 40-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749548
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The development of recombinant human serum albumin. Author(s): Kobayashi K, Nakamura N, Sumi A, Ohmura T, Yokoyama K. Source: Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis. 1998 November; 2(4): 257-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227751
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The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations. Author(s): Levraut J, Garcia P, Giunti C, Ichai C, Bouregba M, Ciebiera JP, Payan P, Grimaud D. Source: Intensive Care Medicine. 2000 May; 26(5): 558-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923730
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The influence of albumin on corrosion resistance of titanium in fluoride solution. Author(s): Ide K, Hattori M, Yoshinari M, Kawada E, Oda Y. Source: Dent Mater J. 2003 September; 22(3): 359-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621001
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The ischemia-modified albumin biomarker for myocardial ischemia. Author(s): Wu AH. Source: Mlo: Medical Laboratory Observer. 2003 June; 35(6): 36-8, 40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841070
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The structure of the sugar residue in glycated human serum albumin and its molecular recognition by phenylboronate. Author(s): Rohovec J, Maschmeyer T, Aime S, Peters JA. Source: Chemistry (Weinheim an Der Bergstrasse, Germany). 2003 May 23; 9(10): 2193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772293
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Time-resolved fluorescence resonance energy transfer assay for point-of-care testing of urinary albumin. Author(s): Qin QP, Peltola O, Pettersson K. Source: Clinical Chemistry. 2003 July; 49(7): 1105-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816907
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Treatment of cirrhotic tense ascites with Dextran-40 versus albumin associated with large volume paracentesis: a randomized controlled trial. Author(s): Garcia-Compean D, Blanc P, Larrey D, Daures JP, Hirtz J, Mendoza E, Maldonado H, Michel H. Source: Ann Hepatol. 2002 January-March; 1(1): 29-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114293
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Unique, pH-dependent biphasic band shape of the visible circular dichroism of curcumin-serum albumin complex. Author(s): Zsila F, Bikadi Z, Simonyi M. Source: Biochemical and Biophysical Research Communications. 2003 February 14; 301(3): 776-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12565848
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Uptake of proteins and degradation of human serum albumin by Plasmodium falciparum-infected human erythrocytes. Author(s): El Tahir A, Malhotra P, Chauhan VS. Source: Malaria Journal [electronic Resource]. 2003 May 07; 2(1): 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801422
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Urinary albumin excretion and its relationship to C-reactive protein and proinflammatory cytokines in patients with cancer and febrile neutropenia. Author(s): Pedersen LM, Bergmann OJ. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(8): 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514150
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Urinary albumin excretion predicts cardiovascular and non-cardiovascular mortality in general population. Author(s): Hollenberg NK. Source: Current Hypertension Reports. 2003 October; 5(5): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531407
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Urinary albumin to osmolality ratio predicts 24-hour urine albumin excretion in diabetes mellitus. Author(s): Gyamlani GG, Bergstralh EJ, Slezak JM, Larson TS. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 October; 42(4): 685-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520618
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Urinary concentrations of alpha-1-microglobulin and albumin in patients with reflux nephropathy before and after puberty. Author(s): Konda R, Kakizaki H, Nakai H, Hayashi Y, Hosokawa S, Kawaguchi S, Matuoka H, Nonomura K; Reflux Nephrology Forum, Japanese Prospective Study Group. Source: Nephron. 2002 December; 92(4): 812-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399625
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Use of albumin in the intensive care unit. Author(s): Dubois MJ, Vincent JL. Source: Current Opinion in Critical Care. 2002 August; 8(4): 299-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386489
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Use of albumin in the management of patients with decompensated cirrhosis. An independent verdict. Author(s): Arroyo V, Colmenero J. Source: Dig Liver Dis. 2003 September; 35(9): 668-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563192
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Use of amphotericin B as optical probe to study conformational changes and thermodynamic stability in human serum albumin. Author(s): Romanini D, Muller G, Pico G. Source: Journal of Protein Chemistry. 2002 November; 21(8): 505-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12638652
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Using a creatinine ratio in urinalysis to improve the reliability of protein and albumin results. Author(s): Ehrmeyer S. Source: Mlo: Medical Laboratory Observer. 2003 January; 35(1): 26-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12561743
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Validation of albumin determined in urine with the HemoCue point-of-care analyser. Author(s): von Schenck H. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2003; 63(2): 11926. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751693
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Validation of the chloramine-T induced oxidation of human serum albumin as a model for oxidative damage in vivo. Author(s): Anraku M, Kragh-Hansen U, Kawai K, Maruyama T, Yamasaki Y, Takakura Y, Otagiri M. Source: Pharmaceutical Research. 2003 April; 20(4): 684-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739779
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Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan. Author(s): van Ginkel RJ, Limburg PC, Piers DA, Koops HS, Hoekstra HJ. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2002 May; 9(4): 355-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986187
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Variability in aflatoxin-albumin adduct levels and effects of hepatitis B and C virus infection and glutathione S-transferase M1 and T1 genotype. Author(s): Ahsan H, Wang LY, Chen CJ, Tsai WY, Santella RM. Source: Environmental Health Perspectives. 2001 August; 109(8): 833-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564620
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Variability of standard clinical protein assays in the analysis of a model urine solution of fragmented albumin. Author(s): Eppel GA, Nagy S, Jenkins MA, Tudball RN, Daskalakis M, Balazs ND, Comper WD. Source: Clinical Biochemistry. 2000 August; 33(6): 487-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074241
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Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system. Author(s): Bardoux P, Bichet DG, Martin H, Gallois Y, Marre M, Arthus MF, Lonergan M, Ruel N, Bouby N, Bankir L. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 March; 18(3): 497-506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584270
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Vertebral hemangioma demonstrated by Tc-99m DTPA-human serum albumin SPECT. Author(s): Demizu Y, Yamaji S, Takada Y. Source: Clinical Nuclear Medicine. 2002 February; 27(2): 126-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786743
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Visualizing false lumen perfusion using sonicated albumin microspheres in aortic dissection repair: a state of the art application of contrast echocardiography and echoaortography. Author(s): Shapiro MA, Feinstein S. Source: Critical Care Medicine. 2000 June; 28(6): 2147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890687
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Vitamin D deficiency is implicated in reduced serum albumin concentrations in patients with end-stage renal disease. Author(s): Yonemura K, Fujimoto T, Fujigaki Y, Hishida A. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 August; 36(2): 337-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10922312
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Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Author(s): Sedrakyan A, Gondek K, Paltiel D, Elefteriades JA. Source: Chest. 2003 June; 123(6): 1853-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796160
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Water-proton relaxation by a noncovalent albumin-binding gadolinium chelate: an NMRD study of a potential blood pool agent. Author(s): Adzamli K, Spiller M, Koenig SH. Source: Academic Radiology. 2002 May; 9 Suppl 1: S11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019842
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What's the serum albumin? Author(s): Everitt N. Source: Annals of the Royal College of Surgeons of England. 1998 September; 80(5): 3756. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9849350
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When is an albumin infusion needed? Author(s): Fischer J. Source: Dimensions of Critical Care Nursing : Dccn. 1999 July-August; 18(4): 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10640024
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White blood cell count is positively correlated with albumin excretion rate in subjects with type 2 diabetes. Author(s): Cavalot F, Massucco P, Perna P, Traversa M, Anfossi G, Trovati M. Source: Diabetes Care. 2002 December; 25(12): 2354-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453989
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Why measure serum albumin levels? Author(s): Kaysen GA, Levin NW. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2002 July; 12(3): 148-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12105811
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Yeast-derived recombinant human albumin (Recombumin). Author(s): Ballance DJ. Source: Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : Ains. 1999 December; 34(12): 775-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10665315
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CHAPTER 2. NUTRITION AND ALBUMIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and albumin.
Finding Nutrition Studies on Albumin 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 “albumin” (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 albumin: •
Animal versus plant protein meals in individuals with type 2 diabetes and microalbuminuria: effects on renal, glycemic, and lipid parameters. Author(s): Diabetes Research and Training Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
[email protected] Source: Wheeler, M L Fineberg, S E Fineberg, N S Gibson, R G Hackward, L L DiabetesCare. 2002 August; 25(8): 1277-82 0149-5992
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Antibodies against bovine albumin and other diabetes markers in French children. Author(s): INSERM CJF 93-13, Hopital Robert Debre, Paris, France. Source: Levy Marchal, C Karjalainen, J Dubois, F Karges, W Czernichow, P Dosch, H M Diabetes-Care. 1995 August; 18(8): 1089-94 0149-5992
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Cow's milk, bovine serum albumin, and IDDM: can we settle the controversies? Author(s): Hospital For Sick Children, Research Institute, Toronto, Canada. Source: Hammond McKibben, D Dosch, H M Diabetes-Care. 1997 May; 20(5): 897-901 0149-5992
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Detection by competitive enzyme-linked immunosorbent assay of a bovine serum albumin peptide (ABBOS) in infant formulas based on hydrolyzed cow's milk protein. Author(s): Department of Nutrition, Netherlands Institute for Dairy Research (NIZO), Ede, The Netherlands. Source: van Beresteijn, E C Meijer, R J Diabetes-Care. 1996 December; 19(12): 1364-9 0149-5992
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Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators. Author(s): West Los Angeles Veterans Affairs Medical Center, California 90073, USA.
[email protected] Source: Levin, S R Coburn, J W Abraira, C Henderson, W G Colwell, J A Emanuele, N V Nuttall, F Q Sawin, C T Comstock, J P Silbert, C K Diabetes-Care. 2000 October; 23(10): 1478-85 0149-5992
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Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Author(s): Department of Medicine, Jawahar Lal Nehru Medical College and Hospital, Aligarh Muslim University, India. Source: Ahmad, J Siddiqui, M A Ahmad, H Diabetes-Care. 1997 October; 20(10): 1576-81 0149-5992
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Evolution, risk factors, and prognostic implications of albuminuria in NIDDM. Author(s): Department of Clinical Nutrition, University of Kuopio, Finland.
[email protected] Source: Niskanen, L K Penttila, I Parviainen, M Uusitupa, M I Diabetes-Care. 1996 May; 19(5): 486-93 0149-5992
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Higher intakes of fish protein are related to a lower risk of microalbuminuria in young Swedish type 1 diabetic patients. Author(s): Department of Clinical Sciences, Paediatrics, Umea University, Sweden. Source: Mollsten, A V Dahlquist, G G Stattin, E L Rudberg, S Diabetes-Care. 2001 May; 24(5): 805-10 0149-5992
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Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria. Author(s): Department of Medicine, University of Chieti, Italy.
[email protected] Source: Chiarelli, F Catino, M Tumini, S de Martino, M Mezzetti, A Verrotti, A Vanelli, M Diabetes-Care. 1999 July; 22(7): 1158-64 0149-5992
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Increased small dense LDL and intermediate-density lipoprotein with albuminuria in type 1 diabetes. Author(s): Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle 98195, USA.
[email protected] Source: Sibley, S D Hokanson, J E Steffes, M W Purnell, J Q Marcovina, S M Cleary, P A Brunzell, J D Diabetes-Care. 1999 July; 22(7): 1165-70 0149-5992
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Lack of impact of low-dose acetylsalicylic acid on kidney function in type 1 diabetic patients with microalbuminuria. Author(s): Steno Diabetes Center, Copenhagen, Denmark. Source: Hansen, H P Gaede, P H Jensen, B R Parving, H H Diabetes-Care. 2000 December; 23(12): 1742-5 0149-5992
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Long-term lisinopril therapy reduces exercise-induced albuminuria in normoalbuminuric normotensive IDDM patients. Author(s): Department of Medicine, Helsinki University Central Hospital, Finland.
[email protected] Source: Tuominen, J A Ebeling, P Koivisto, V A Diabetes-Care. 1998 August; 21(8): 13458 0149-5992
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Microalbuminuria in a middle-aged workforce. Effect of hyperglycemia and ethnicity. Author(s): Department of Community Health, University of Auckland, New Zealand. Source: Metcalf, P A Baker, J R Scragg, R K Dryson, E Scott, A J Wild, C J Diabetes-Care. 1993 November; 16(11): 1485-93 0149-5992
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Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators. Author(s): McMaster University, Hamilton, Ontario, Canada.
[email protected] Source: Gerstein, H C Mann, J F Pogue, J Dinneen, S F Halle, J P Hoogwerf, B Joyce, C Rashkow, A Young, J Zinman, B Yusuf, S Diabetes-Care. 2000 April; 23 Suppl 2B35-9 0149-5992
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Proteinuria and albumin homeostasis in the nephrotic syndrome: effect of dietary protein intake. Author(s): Department of Experimental Medicine, University of Chile, Santiago. Source: Rodrigo, R Bravo, I Pino, M Nutr-Revolume 1996 November; 54(11 Pt 1): 337-47 0029-6643
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Reduced albuminuria after dietary protein restriction in insulin-dependent diabetic patients with clinical nephropathy. Source: Ciavarella, A Di Mizio, G Stefoni, S Borgnino, L C Vannini, P Diabetes-Care. 1987 Jul-August; 10(4): 407-13 0149-5992
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Relationship between lipoprotein profile and urinary albumin excretion in type II diabetic patients with stable metabolic control. Source: Reverter, J.L. Senti, M. Rubies Prat, J. Lucas, A. Salinas, I. Pizarro, E. Pedro Botet, J. Romero, R. Sanmarti, A. Diabetes-care (USA). (Mar 1994). volume 17(3) page 189-194. diabetes lipoproteins albumins urine men women 0149-5992
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Relative clinical usefulness of glycosylated serum albumin and fructosamine during short-term changes in glycemic control in IDDM. Author(s): Department of Medicine, University of Manchester, Hope Hospital, Salford, United Kingdom. Source: Winocour, P H Bhatnagar, D Kalsi, P Hillier, V F Anderson, D C Diabetes-Care. 1989 Nov-December; 12(10): 665-72 0149-5992
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Similar insulin sensitivity in NIDDM patients with normo- and microalbuminuria. Author(s): Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark. Source: Nielsen, S Schmitz, O Orskov, H Mogensen, C E Diabetes-Care. 1995 June; 18(6): 834-42 0149-5992
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Sodium sensitivity related to albuminuria appearing before hypertension in type 2 diabetic patients. Author(s): Department of Medicine, Osaka City General Hospital, Osaka, Japan.
[email protected] Source: Imanishi, M Yoshioka, K Okumura, M Konishi, Y Okada, N Morikawa, T Sato, T Tanaka, S Fujii, S Diabetes-Care. 2001 January; 24(1): 111-6 0149-5992
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The relationship among homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes. Author(s): Department of Diabetes, Endocrinology, and Metabolism, Royal North Shore Hospital, St. Leonards, Australia. Source: Davies, L Wilmshurst, E G McElduff, A Gunton, J Clifton Bligh, P Fulcher, G R Diabetes-Care. 2001 October; 24(10): 1805-9 0149-5992
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Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction. Author(s): University of Melbourne, Department of Medicine at Austin, Victoria, Australia. Source: Houlihan, C A Akdeniz, A Tsalamandris, C Cooper, M E Jerums, G Gilbert, R E Diabetes-Care. 2002 June; 25(6): 1072-7 0149-5992
The following information is typical of that found when using the “Full IBIDS Database” to search for “albumin” (or a synonym): •
Amadori product and age formation during nonenzymatic glycosylation of bovine serum albumin in vitro. Author(s): Department of Life Sciences, University of Bombay, Santacruz (E), Mumbai 400 098, India. Source: Sharma, S D Pandey, B N Mishra, K P Sivakami, S J-Biochem-Mol-Biol-Biophys. 2002 August; 6(4): 233-42 1025-8140
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Application of affinity capillary electrophoresis for the determination of binding and thermodynamic constants of enediynes with bovine serum albumin. Author(s): Department of Chemistry, 102 HT Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. Source: El Shafey, Ahmed Zhong, Huijuan Jones, Graham Krull, Ira S Electrophoresis. 2002 March; 23(6): 945-50 0173-0835
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Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Author(s): Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Source: Abu Qare, A W Abou Donia, M B Arch-Toxicol. 2002 May; 76(4): 203-8 03405761
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Correlation between the osmotic second virial coefficient and solubility for equine serum albumin and ovalbumin. Author(s): Department of Chemistry, Mississippi State University, Box 9573, Mississippi State, MS 39762, USA. Source: Demoruelle, K Guo, B Kao, S McDonald, H M Nikic, D B Holman, S C Wilson, W W Acta-Crystallogr-D-Biol-Crystallogr. 2002 October; 58(Pt 10 Pt 1): 1544-8 0907-4449
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Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein binding. Author(s): Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486-0004, USA.
[email protected] Source: Tang, C Lin, Y Rodrigues, A D Lin, J H Drug-Metab-Dispos. 2002 June; 30(6): 648-54 0090-9556
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Enzymatic degradation of and bovine serum albumin release from starch-acetate films. Author(s): Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN70211 Kuopio, Finland.
[email protected] Source: Tuovinen, Laura M Peltonen, Soili H Suortti, Tapani M Crowther, Nicholas J Elomaa, Matti A Jarvinen, Kristiina P Biomacromolecules. 2002 Mar-April; 3(2): 284-90 1525-7797
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High albumin levels restrict the kinetics of 13-cis retinoic acid uptake and intracellular isomerization to all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes. Author(s): Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany. Source: Tsukada, M Schroder, M Seltmann, H Orfanos, C E Zouboulis, C C J-InvestDermatol. 2002 July; 119(1): 182-5 0022-202X
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Human serum albumin adsorption onto a-SiC:H and a-C:H thin films deposited by plasma enhanced chemical vapor deposition. Author(s): Department of Chemistry, University of Catania, v. A.Doria, 6-95125 Catania, Italy. Source: Auditore, A Satriano, C Coscia, U Ambrosone, G Parisi, V Marletta, G BiomolEng. 2002 August; 19(2-6): 85-90 1389-0344
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Identification of drug-binding sites on human serum albumin using affinity capillary electrophoresis and chemically modified proteins as buffer additives. Author(s): Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA. Source: Kim, Hee Seung Austin, John Hage, David S Electrophoresis. 2002 March; 23(6): 956-63 0173-0835
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Influence of structure of human, rat, and bovine serum albumins on binding properties of photoactive drug hypericin. Author(s): Department of Biophysics, P. J. Safarik University, Jesenna 5, 041 54 Kosice, Slovak Republic.
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Source: Hritz, Jozef Kascakova, Slavka Ulicny, Jozef Miskovsky, Pavol Biopolymers. 2002; 67(4-5): 251-4 0006-3525 •
Measurement of blood volume after haemodilution with haemoglobin-based oxygen carriers by a radiolabelled-albumin method. Author(s): Department of Haematology and Physiology, University Henri PoincareNancy 1, 5 rue Albert Lebrun, 54001 Nancy cedex, France.
[email protected] Source: Caron, A Mayer, J C Menu, P Alayash, A Marie, P Y Vigneron, C Transfus-Med. 2001 December; 11(6): 433-42 0958-7578
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Measurement of S-nitrosoalbumin by gas chromatography--mass spectrometry. III. Quantitative determination in human plasma after specific conversion of the Snitroso group to nitrite by cysteine and Cu(2+) via intermediate formation of Snitrosocysteine and nitric oxide. Author(s): Institute of Clinical Pharmacology, Hannover Medical School, Carl-NeubergStrasse 1, D-30625, Hannover, Germany.
[email protected] Source: Tsikas, Dimitrios Sandmann, Jorg Frolich, Jurgen C J-Chromatogr-B-AnalytTechnol-Biomed-Life-Sci. 2002 June 5; 772(2): 335-46 1570-0232
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Peculiar chiral discrimination of bovine serum albumin to (+/-)-N-dansyl-norleucine. Author(s): Kyoritsu College of Pharmacy, Minato, Tokyo, Japan.
[email protected] Source: Abe, Y Yasuoka, S Shoji, T Sugata, S Hattori, K Iwata, K Suzuki, H Anal-Sci. 2002 July; 18(7): 823-5 0910-6340
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Pharmacokinetic analysis of lectin-dependent biodistribution of fucosylated bovine serum albumin: a possible carrier for Kupffer cells. Author(s): Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan. Source: Opanasopit, P Nishikawa, M Yamashita, F Takakura, Y Hashida, M J-DrugTarget. 2001; 9(5): 341-51 1061-186X
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Piezoelectric quartz crystal impedance study of the Pb2+-induced precipitation of bovine serum albumin and its dissolution with EDTA in an aqueous solution. Author(s):
[email protected] Source: Yuan, Y Cai, Y Xie, Q Yao, S Anal-Sci. 2002 July; 18(7): 767-71 0910-6340
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Raman and surface enhanced Raman spectroscopy of 2,2,5,5-tetramethyl-3-pyrrolin-1yloxy-3-carboxamide labeled proteins: bovine serum albumin and cytochrome c. Author(s): Biophysics Department, University of Oradea, 1 Dec. Square, Number 10, RO-3700 Oradea, Romania.
[email protected] Source: Cavalu, S Cinta Pinzaru, S Leopold, N Kiefer, W Biopolymers. 2001; 62(6): 341-8 0006-3525
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Reduction of plasma triglyceride level and enhancement of plasma albumin concentration by Oren-gedoku-to administration. Author(s): Department of Japanese Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University.
[email protected] Source: Sekiya, N Kogure, T Kita, T Kasahara, Y Sakakibara, I Goto, H Shibahara, N Shimada, Y Terasawa, K Phytomedicine. 2002 July; 9(5): 455-60 0944-7113
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Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymermodified poly(ether urethane) surfaces. Author(s): Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, PR China.
[email protected] Source: Wang, D A Ji, J Feng, L X J-Biomater-Sci-Polym-Ed. 2001; 12(10): 1123-46 09205063
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Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction. Author(s): Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
[email protected] Source: Fitos, Ilona Visy, Julia Kardos, Julianna Chirality. 2002 May 15; 14(5): 442-8 08990042
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Structural insights into human serum albumin-mediated prostaglandin catalysis. Author(s): Department of Biochemistry and Biophysics, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96822, USA.
[email protected] Source: Yang, J Petersen, C E Ha, C E Bhagavan, N V Protein-Sci. 2002 March; 11(3): 53845 0961-8368
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Successful treatment of hypoalbuminemic hemodialysis patients with a modified regimen of oral essential amino acids. Author(s): Gambro Healthcare, J. B. Zachary Dialysis Unit, Johns Hopkins Bayview Hospital, Baltimore, MD 21205, USA. Source: Bronich, L Te, T Shetye, K Stewart, T Eustace, J A J-Ren-Nutr. 2001 October; 11(4): 194-201 1051-2276
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Use of an immobilised human serum albumin HPLC column as a probe of drugprotein interactions: the reversible binding of valproate. Author(s): Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Italy.
[email protected] Source: Bertucci, C Andrisano, V Gotti, R Cavrini, V J-Chromatogr-B-Analyt-TechnolBiomed-Life-Sci. 2002 February 25; 768(1): 147-55 1570-0232
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Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal nuclear envelope of round spermatids of a rat injected intravenously with gold labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from acrosome to nucleus. Author(s): Department of Anatomy, Aichi Medical University School of Medicine, Yazako, Japan.
[email protected] Source: Nishimura, T Nakano, T Okajimas-Folia-Anat-Jpn. 2002 May; 79(1): 15-23 0030154X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to albumin; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Clorazepate Dipotassium Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet Cinnamon Alternative names: Cinnamomum zeylanicum Source: Healthnotes, Inc.; www.healthnotes.com Egg-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND ALBUMIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to albumin. 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 albumin 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 “albumin” (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 albumin: •
A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings. Author(s): Damascelli B, Patelli GL, Lanocita R, Di Tolla G, Frigerio LF, Marchiano A, Garbagnati F, Spreafico C, Ticha V, Gladin CR, Palazzi M, Crippa F, Oldini C, Calo S, Bonaccorsi A, Mattavelli F, Costa L, Mariani L, Cantu G. Source: Ajr. American Journal of Roentgenology. 2003 July; 181(1): 253-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818869
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ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study. Author(s): de Azevedo MJ, Dalmaz CA, Caramori ML, Pecis M, Esteves JF, Maia AL, Gross JL. Source: Journal of Diabetes and Its Complications. 2002 July-August; 16(4): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126783
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Albumin enhanced morphometric image analysis in CLL. Author(s): Lunning MA, Zenger VE, Dreyfuss R, Stetler-Stevenson M, Rick ME, White TA, Wilson WH, Marti GE. Source: Cytometry : the Journal of the Society for Analytical Cytology. 2004 January; 57B(1): 7-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696058
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Albumin uptake and transcytosis in endothelial cells in vivo induced by albuminbinding protein. Author(s): Vogel SM, Minshall RD, Pilipovic M, Tiruppathi C, Malik AB. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2001 December; 281(6): L1512-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704548
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Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Lepr db/+Lepr db (db/db) mice. Author(s): Teixeira SR, Tappenden KA, Erdman JW Jr. Source: The Journal of Nutrition. 2003 March; 133(3): 673-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612136
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Analysis of an expanded width of albumin fraction by cellulose acetate membrane electrophoresis in IgA nephropathy urine before treatment. Author(s): Machii R, Matsuda K, Hiratsuka N, Sugimoto K, Hotta O, Itoh Y, Yoshida H, Shiba K. Source: Journal of Clinical Laboratory Analysis. 2003; 17(2): 37-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640625
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Binding of Amadori glucose-modified albumin by the monocytic cell line MonoMac 6 activates protein kinase C epsilon protein tyrosine kinases and the transcription factors AP-1 and NF-kappaB. Author(s): Salazar R, Brandt R, Krantz S. Source: Glycoconjugate Journal. 2001 October; 18(10): 769-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441666
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Binding of quercetin with human serum albumin: a critical spectroscopic study. Author(s): Sengupta B, Sengupta PK. Source: Biopolymers. 2003; 72(6): 427-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587065
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Differential effect of bovine serum albumin on ginsenoside metabolite-induced inhibition of alpha3beta4 nicotinic acetylcholine receptor expressed in Xenopus oocytes. Author(s): Lee JH, Jeong SM, Lee BH, Kim DH, Kim JH, Kim JI, Lee SM, Nah SY.
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Source: Arch Pharm Res. 2003 October; 26(10): 868-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609137 •
Diurnal variations of glomerular filtration rate and albuminuria in diabetic nephropathy. Author(s): Hansen HP, Hovind P, Jensen BR, Parving HH. Source: Kidney International. 2002 January; 61(1): 163-8. Erratum In: Kidney Int 2002 August; 62(2): 731. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786097
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Effect of charge on interstitial distribution of albumin in rat dermis in vitro. Author(s): Wiig H, Kolmannskog O, Tenstad O, Bert JL. Source: The Journal of Physiology. 2003 July 15; 550(Pt 2): 505-14. Epub 2003 May 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766239
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Effects of albumin supplementation during cardioplegia administration: an in vitro analysis. Author(s): Knox R, Stammers AH, Ellis T, Gao C, Nutter B, Holcomb H, Schmer R, Hock LM. Source: J Extra Corpor Technol. 2003 March; 35(1): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680491
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Effects of Inula Britannica on the production of antibodies and cytokines and on T cell differentiation in C57BL/6 mice immunized by ovalbumin. Author(s): Song QH, Kobayashi T, Hong T, Cyong JC. Source: The American Journal of Chinese Medicine. 2002; 30(2-3): 297-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230018
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Effects of xiao-qing-long-tang (XQLT) on bronchoconstriction and airway eosinophil infiltration in ovalbumin-sensitized guinea pigs: in vivo and in vitro studies. Author(s): Kao ST, Lin CS, Hsieh CC, Hsieh WT, Lin JG. Source: Allergy. 2001 December; 56(12): 1164-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736745
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Endotoxin removal in some medicines and human serum albumin solution by affinity membranes. Author(s): Wei GL, Liu XL, Li JH, Liu Y, Shang ZH. Source: Se Pu. 2002 March; 20(2): 108-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12541963
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Estimation of parvalbumin Ca(2+)- and Mg(2+)-binding constants by global leastsquares analysis of isothermal titration calorimetry data. Author(s): Henzl MT, Larson JD, Agah S.
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Source: Analytical Biochemistry. 2003 August 15; 319(2): 216-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871715 •
Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys. Author(s): Lund U, Rippe A, Venturoli D, Tenstad O, Grubb A, Rippe B. Source: American Journal of Physiology. Renal Physiology. 2003 June; 284(6): F1226-34. Epub 2003 March 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620929
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Glycated albumin increases oxidative stress, activates NF-kappa B and extracellular signal-regulated kinase (ERK), and stimulates ERK-dependent transforming growth factor-beta 1 production in macrophage RAW cells. Author(s): Cohen MP, Shea E, Chen S, Shearman CW. Source: The Journal of Laboratory and Clinical Medicine. 2003 April; 141(4): 242-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677169
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Glycomacropeptide and alpha-lactalbumin supplementation of infant formula affects growth and nutritional status in infant rhesus monkeys. Author(s): Kelleher SL, Chatterton D, Nielsen K, Lonnerdal B. Source: The American Journal of Clinical Nutrition. 2003 May; 77(5): 1261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716681
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In vitro Behaviour of Sesquiterpene Lactones and Sesquiterpene Lactone-Containing Plant Preparations in Human Blood, Plasma and Human Serum Albumin Solutions. Author(s): Wagner S, Kratz F, Merfort I. Source: Planta Medica. 2004 March; 70(3): 227-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114499
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In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle. Author(s): Gyenge CC, Tenstad O, Wiig H. Source: The Journal of Physiology. 2003 November 1; 552(Pt 3): 907-16. Epub 2003 August 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937287
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Increased glomerular albumin permeability in old spontaneously hypertensive rats. Author(s): Bakoush O, Tencer J, Torffvit O, Tenstad O, Skogvall I, Rippe B. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2004 April 21 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102963
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Interaction of magnolol with bovine serum albumin: a fluorescence-quenching study. Author(s): Liu J, Tian JN, Zhang J, Hu Z, Chen X. Source: Analytical and Bioanalytical Chemistry. 2003 July; 376(6): 864-7. Epub 2003 June 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830359
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Interstitial exclusion of albumin in rabbit lung during development of pulmonary oedema. Author(s): Negrini D, Tenstad O, Wiig H. Source: The Journal of Physiology. 2003 May 1; 548(Pt 3): 907-17. Epub 2003 March 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651921
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Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity. Author(s): Damascelli B, Cantu G, Mattavelli F, Tamplenizza P, Bidoli P, Leo E, Dosio F, Cerrotta AM, Di Tolla G, Frigerio LF, Garbagnati F, Lanocita R, Marchiano A, Patelli G, Spreafico C, Ticha V, Vespro V, Zunino F. Source: Cancer. 2001 November 15; 92(10): 2592-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745194
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Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy. Author(s): Myrup B, Rossing P, Jensen T, Parving HH, Holmer G, Gram J, Kluft C, Jespersen J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2001; 61(5): 34956. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11569481
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Long-term stabilization of recombinant human interferon alpha 2b in aqueous solution without serum albumin. Author(s): Ruiz L, Reyes N, Duany L, Franco A, Aroche K, Hardy Rando E. Source: International Journal of Pharmaceutics. 2003 October 2; 264(1-2): 57-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972336
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Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Author(s): Das M, Ram A, Ghosh B. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 March; 52(3): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755373
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Maleimide-oligo(ethylene glycol) derivatives of camptothecin as albumin-binding prodrugs: synthesis and antitumor efficacy. Author(s): Warnecke A, Kratz F. Source: Bioconjugate Chemistry. 2003 March-April; 14(2): 377-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643748
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Maternal dietary N-3 fatty acids alter the spleen fatty acid composition and bovine serum albumin-induced wing web swelling in broilers. Author(s): Wang YW, Ajuyah AO, Sunwoo HH, Cherian G, Sim JS. Source: Poultry Science. 2002 November; 81(11): 1722-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455601
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Nitric oxide increases albumin permeability of isolated rat glomeruli via a phosphorylation-dependent mechanism. Author(s): Li B, Yao J, Morioka T, Oite T. Source: Journal of the American Society of Nephrology : Jasn. 2001 December; 12(12): 2616-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729230
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Piezoelectric quartz crystal impedance study of the Pb2+-induced precipitation of bovine serum albumin and its dissolution with EDTA in an aqueous solution. Author(s): Yuan Y, Cai Y, Xie Q, Yao S. Source: Anal Sci. 2002 July; 18(7): 767-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137371
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Pyridoindole antioxidant stobadine protected bovine serum albumin against the hydroxyl radical mediated cross-linking in vitro. Author(s): Kyselova Z, Rackova L, Stefek M. Source: Archives of Gerontology and Geriatrics. 2003 May-June; 36(3): 221-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849078
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Rabbit serum albumin hydrolyzes the carbamate carbaryl. Author(s): Sogorb MA, Carrera V, Benabent M, Vilanova E. Source: Chemical Research in Toxicology. 2002 April; 15(4): 520-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952338
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Raman and surface enhanced Raman spectroscopy of 2,2,5,5-tetramethyl-3-pyrrolin-1yloxy-3-carboxamide labeled proteins: bovine serum albumin and cytochrome c. Author(s): Cavalu S, Cinta-Pinzaru S, Leopold N, Kiefer W. Source: Biopolymers. 2001; 62(6): 341-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857273
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Reduction of plasma triglyceride level and enhancement of plasma albumin concentration by Oren-gedoku-to administration. Author(s): Sekiya N, Kogure T, Kita T, Kasahara Y, Sakakibara I, Goto H, Shibahara N, Shimada Y, Terasawa K. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 July; 9(5): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222668
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Roles of IL-4 and other factors in the trichosanthin-induced ovalbumin-specific IgE response. Author(s): Xu WF, Ji YY, Wu YD, Lin GM, Ye M, Sun B. Source: Acta Pharmacologica Sinica. 2001 August; 22(8): 736-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749848
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Separation of alpha-lactalbumin and beta-lactoglobulin using membrane ultrafiltration. Author(s): Cheang B, Zydney AL. Source: Biotechnology and Bioengineering. 2003 July 20; 83(2): 201-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768626
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Stability of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in the presence of human serum albumin. Author(s): Prijovich ZM, Leu YL, Roffler SR. Source: Biochemical Pharmacology. 2003 October 1; 66(7): 1181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505797
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Studies on the interaction of total saponins of panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy. Author(s): Liu Y, Xie MX, Kang J, Zheng D. Source: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. 2003 October; 59(12): 2747-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499835
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Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia. Author(s): Yonemura K, Sugiura T, Yamashita F, Matsushima H, Hishida A. Source: Blood Purification. 2004; 22(2): 210-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044820
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Systemic fatty acid responses to transient focal cerebral ischemia: influence of neuroprotectant therapy with human albumin. Author(s): Rodriguez de Turco EB, Belayev L, Liu Y, Busto R, Parkins N, Bazan NG, Ginsberg MD.
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Source: Journal of Neurochemistry. 2002 November; 83(3): 515-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390513 •
The adjuvant activity of lactoferrin in the generation of DTH to ovalbumin can be inhibited by bovine serum albumin bearing alpha-D-mannopyranosyl residues. Author(s): Kocieba M, Zimecki M, Kruzel M, Actor J. Source: Cellular & Molecular Biology Letters. 2002; 7(4): 1131-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511980
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The interaction of quercetin with human serum albumin: a fluorescence spectroscopic study. Author(s): Sengupta B, Sengupta PK. Source: Biochemical and Biophysical Research Communications. 2002 December 6; 299(3): 400-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445814
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The pregnancy-related decrease in fasting plasma homocysteine is not explained by folic acid supplementation, hemodilution, or a decrease in albumin in a longitudinal study. Author(s): Murphy MM, Scott JM, McPartlin JM, Fernandez-Ballart JD. Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 614-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198008
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Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization. Author(s): Whitekus MJ, Li N, Zhang M, Wang M, Horwitz MA, Nelson SK, Horwitz LD, Brechun N, Diaz-Sanchez D, Nel AE. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 March 1; 168(5): 2560-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859152
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Transendothelial transport of low-density lipoprotein and albumin across the rat peritoneum in vivo: effects of the transcytosis inhibitors NEM and filipin. Author(s): Rosengren BI, Al Rayyes O, Rippe B. Source: Journal of Vascular Research. 2002 May-June; 39(3): 230-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097821
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Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal nuclear envelope of round spermatids of a rat injected intravenously with gold labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from acrosome to nucleus. Author(s): Nishimura T, Nakano T.
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Source: Okajimas Folia Anat Jpn. 2002 May; 79(1): 15-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199534
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to albumin; 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 Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Bladder Infection Alternative names: Urinary Tract Infection [UTI] Source: Prima Communications, Inc.www.personalhealthzone.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com
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Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Gestational Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Preeclampsia Source: Healthnotes, Inc.; www.healthnotes.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com •
Chinese Medicine Hongqi Alternative names: Manyinflorescenced Sweetvetch Root; Radix Hedysari Source: Chinese Materia Medica Huangqi Alternative names: Milkvetch; Radix Astragali Source: Chinese Materia Medica
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Herbs and Supplements Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Barberry Alternative names: Berberis vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Goldenseal Source: Prima Communications, Inc.www.personalhealthzone.com
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Kochia Alternative names: Summer Cypress, Fireweed; Kochia scoparia (L.) Schrad Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lipoic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Alternative names: Kava; Piper methysticum Forst.f Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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 ALBUMIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to albumin. 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 “albumin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on albumin, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Albumin 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 albumin. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A fluorometric coupled enzymatic method for the determination of adenosine triphosphate in platelets colorimetric determination of non-enzymatically glycated albumin by Caines, Patrick Stephen Michael; PhD from University of Windsor (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL20737
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Albumin-dye and antibody-hapten interactions by Goldwater, Sydney G; ADVDEG from McGill University (Canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02683
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ANALYSIS OF THE IMPACT OF TECHNOLOGICAL CHANGES IN THE PLASMA DERIVATIVE INDUSTRY ON ITS TWO MAIN PRODUCTS, NORMAL SERUM ALBUMIN AND ANTIHEMOPHILIC FACTOR IN THE UNITED STATES (BLOOD) by GROSSMAN, JERROLD B., DPS from Pace University, 1989, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9007953
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Development of an oral fluid assay for the detection of uncontrolled diabetics using glycated albumin as a marker by Gelormo, David J.; PhD from Lehigh University, 2003, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3073958
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Insights into the amine-induced cleavage of DNA abasic sites; binding of a novel homologous series of anthraquinones to DNA; metalloporphyrin binding to albumin by McKnight, Ruel Earl; PhD from Georgia State University, 2003, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3110214
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Preparation, characterization, and in vivo evaluation of albumin-encapsulated primaquine diphosphate by Green, Michael Dean; PhD from Mercer University, 2003, 211 pages http://wwwlib.umi.com/dissertations/fullcit/3104054
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Separation of hemoglobin-albumin system by gradient ionic strength: Operating conditions by Mui, Kenneth; ME from The Cooper Union for the Advancement of Science and Art, 2003, 123 pages http://wwwlib.umi.com/dissertations/fullcit/1413936
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THE ALBUMIN POLYMORPHISM AND BILIRUBIN BINDING IN RHESUS MONKEYS (MACACA MULATTA) AND YANOMAMA INDIANS (GENETICS, PROTEINS, BRAZIL, VENEZUELA) by LOREY, FREDERICK WILLIAM, PHD from University of California, Davis, 1985, 120 pages http://wwwlib.umi.com/dissertations/fullcit/8521218
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The effect of altering albumin concentration on the renal elimination of organic anions in the isolated perfused kidney by Ortiz, Stephan Rafael; PhD from Long Island University, the Brooklyn Center, 2003, 251 pages http://wwwlib.umi.com/dissertations/fullcit/3086807
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THE EFFECT OF MODERATE PHYSICAL ACTIVITY ON THE PRODUCTION OF ANTIBODY IN RESPONSE TO BOVINE SERUM ALBUMIN IN RATS by SCHULER, PETRA BETTINA, PHD from The University of Alabama, 1994, 75 pages http://wwwlib.umi.com/dissertations/fullcit/9521156
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The immune response of very young rabbits to human serum albumin by Chou, Chitao; ADVDEG from University of Toronto (Canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00731
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 ALBUMIN 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 “albumin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on albumin, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Albumin By performing a patent search focusing on albumin, 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 albumin: •
Adjuvanted vaccine which is substantially free of non-host albumin Inventor(s): Brown; Karen K. (Bayer Corporation, 100 Bayer Rd., Pittsburgh, PA 152059741), Hennessy; Kristina J. (Bayer Corporation, 100 Bayer Rd., Pittsburgh, PA 152059741), Lane; Jennifer K. (Bayer Corporation, 100 Bayer Rd., Pittsburgh, PA 15205-9741), Trump; Sandra L. (Bayer Corporation, 100 Bayer Rd., Pittsburgh, PA 15205-9741) Assignee(s): None Reported Patent Number: 6,682,746 Date filed: March 14, 2002 Abstract: Disclosed herein is a serum-based adjuvanted vaccine which is substantially free of non-host albumin and the use thereof in reducing or preventing post-vaccination systemic reactions. Excerpt(s): The present invention relates to serum-based vaccines that are substantially free of non-host albumin and processes for preparing and using the same. More specifically, the present invention relates to the inventive concept of vaccines that prevent or substantially reduce post-vaccination adverse systemic reactions associated with adjuvanted vaccine regimens. It is known in the art that vaccination of animals with vaccine regimens involving the use of adjuvants can cause adverse systemic reactions. The vaccine regimen can comprise administration of inactivated vaccine containing an adjuvant. Alternately, the vaccine regimen can comprise administration of a modified live vaccine and an inactivated vaccine containing an adjuvant. Illustratively, most feline vaccine regimens comprise administration of a vaccine containing a modified live organism concomitantly with a vaccine containing an inactivated organism and an adjuvant. Associated with these vaccination regimens are adverse systemic post vaccination reactions. For instance, the use of feline leukemia vaccines (FeLV) can cause post-vaccination reactions including excess salivation, vomiting and diarrhea. See the monograph on FEL-O-VAX Lv-K vaccine in the Compendium of Veterinary Products, page 486, Third Edition, 1995-1996. The adverse systemic reactions include anaphylaxis, hypersensitivity and atypical reactions such as vomiting and diarrhea. Contrary to the present inventive concept, the prior art has attributed the above named systemic reactions to the presence of adjuvants, endotoxins, cellular debris residue, high concentration of modified live viruses or high antigenic mass. Dodds, Vaccine Safety and Efficacy Revisited: Autoimmune and Allergic Diseases on the Rise, Vet. Forum, pp 68-71, May, 1993 noted an increase in post-vaccination autoimmune and allergic diseases. Dodds has postulated that the increase is due to the immunological burden on susceptible animals exposed to a combination vaccine containing modified live organisms and adjuvanted, killed bacterins administered at the same time (as the diluent). Dodds also postulated that the immunological burden is produced by the effect of the modified live organisms. Web site: http://www.delphion.com/details?pn=US06682746__
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Albumin in a flexible polymeric container Inventor(s): Baccia; William (McHenry, IL), Card; John Carl (Washington, MI), Eder; Helmut (Kufstein, AT), Habison; Georg (Vienna, AT), Langer; Theodor (Vienna, AT), Lewis, Jr.; James D. (Antioch, IL), Schmidt; Josef (Green Oaks, IL), Vandersande; Johan (Newhall, CA) Assignee(s): Baxter Healthcare S.a. (zurich, Ch), Baxter International Inc. (deerfield, Il) Patent Number: 6,718,735 Date filed: March 19, 2002 Abstract: A flexible polymeric container for holding albumin. The container is made of a sheet of flexible polymeric film formed into a bag having a cavity enclosed by a first wall, an opposing second wall, and seals about a periphery of the first and second walls. The seals join an interior portion of the opposing first and second walls and create a fluid-tight chamber within the cavity of the container for storing a concentration of the albumin. A method of packaging the albumin protein into a flexible polymeric container is also provided. Therein a flexible polymeric material is converted into bags, the bags are filled with a quantity of albumin by a filler, and a seal area of the bags is sealed to enclose the albumin within the bag. Excerpt(s): The present invention relates generally to the packaging of a protein in a flexible polymeric container, and more specifically to the mass-packaging of albumin in flexible polymeric containers in an aseptic environment of a form-fill-seal packaging machine. Many peptides and proteins for pharmaceutical or other use are known, including glycoproteins, lipoproteins, imunoglobulins, monoclonal antibodies, enzymes, blood proteins, receptor proteins, and hormones. One type of such compound is albumin. Albumin is a sulfur-containing, water-soluble protein that congeals when heated, and occurs in blood. Albumin is often utilized as a blood expander to assist in maintaining a patient's blood pressure, or sometimes to assist with increasing a patient's blood pressure during blood loss. Web site: http://www.delphion.com/details?pn=US06718735__
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Albumin-free Factor VIII formulations Inventor(s): Besman; Marc (Studio City, CA), Bjornson; Erik (Studio City, CA), Carpenter; John (Littleton, CO), Jameel; Feroz (Covina, CA), Kashi; Ramesh (Walnut, CA), Pikal; Michael (Mansfield Center, CT), Tchessalov; Serguei (Ashfor, CT) Assignee(s): Baxter International Inc. (deerfield, Il), University of Connecticut (farmington, Ct) Patent Number: 6,586,573 Date filed: February 22, 2000 Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM
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calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent. Excerpt(s): Factor VIII is a protein found in blood plasma which acts as a cofactor in the cascade of reactions leading to blood coagulation. A deficiency in the amount of Factor VIII activity in the blood results in the clotting disorder known as hemophilia A, an inherited condition primarily affecting males. Hemophilia A is currently treated with therapeutic preparations of Factor VIII derived from human plasma or manufactured using recombinant DNA technology. Such preparations are administered either in response to a bleeding episode (on-demand therapy) or at frequent, regular intervals to prevent uncontrolled bleeding (prophylaxis). Factor VIII is known to be relatively unstable in therapeutic preparations. In blood plasma, Factor VIII is usually complexed with another plasma protein, von Willebrand factor (vWF), which is present in plasma in a large molar excess to Factor VIII and is believed to protect Factor VIII from premature degradation. Another circulating plasma protein, albumin, may also play a role in stabilizing Factor VIII in vivo. Currently marketed Factor VIII preparations therefore primarily rely on the use of albumin and/or vWF to stabilize Factor VIII during the manufacturing process and during storage. The albumin and vWF used in currently marketed Factor VIII preparations is derived from human blood plasma, however, and the use of such material has certain drawbacks. Because a large molar excess of albumin compared to Factor VIII is generally added in order to increase the stability of the Factor VIII in such preparations, it is difficult to characterize the Factor VIII protein itself in these preparations. The addition of human-derived albumin to Factor VIII is also perceived as being a disadvantage with respect to recombinantlyproduced Factor VIII preparations. This is because recombinantly-derived Factor VIII preparations, in the absence of such added albumin, would otherwise contain no human-derived proteins, and the theoretical risk of transmitting a virus would be reduced. Web site: http://www.delphion.com/details?pn=US06586573__ •
Antineoplastic conjugates of transferin, albumin and polyethylene glycol Inventor(s): Kratz; Felix (Muhlenweg 3, 79232 Maseh, DE) Assignee(s): None Reported Patent Number: 6,709,679 Date filed: August 20, 2001 Abstract: Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS--, HO-- or H.sub.2 N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5'-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=--NH.sub.2, --OH, --COOH, --O--CO--R--COR*, --NH--CO--R--COR*, where R is an aliphatic carbon chain with 1-6
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carbon atoms or a substituted or unsubstituted phenylene group and R*H, phenyl, alkyl with 1-6 carbon atoms. Excerpt(s): This invention relates to tumor-inhibiting conjugates of proteins and polymers consisting of a suitable carrier system and cytostatic compounds. Further, the invention relates to methods for the production of such conjugates and the use of these. Immuno-conjugates or conjugates of protein or of polymer are compounds which consist of a suitable carrier substance, such as, for example, an antibody, a growth factor, a structure similar to hormones or peptides, a protein or a polymer, and one or more cytotoxic active substances such as, for example, cytostatics, toxins or radioactive isotopes. The carrier substances have, as a rule, the characteristic of preferably accumulating in the tumor tissue, so that in this way also the active substance bound to the carrier substance accumulates in the tumor tissue and thus a selective anti-tumor therapy is achieved. Chemoimmuno-conjugates are conjugates of carrier substances and cytostatic compounds, wherein the carrier, as a rule, is an antibody. The cytostatics currently used against cancers have a series of strong systemic side-effects and do not exhibit accumulation in the tumor tissue, so that new derivatives and formulations are being researched which make selective anti-tumor therapy possible. For this purpose. chemoimmuno-conjugates or conjugates of proteins or of polymers consisting of one suitable carrier substance or cytostatics are being developed. As carrier substances, among others, antibodies, growth factors, serum proteins, structures similar to hormones or peptides, or polymers are considered, for which, as a rule, an accumulation in the tumor tissue is known (Magerstadt, M.: Antibody Conjugates and Malignant Disease, Library of Congress 1990: Chadwick, C. M.: Receptors in Tumour Biology, Cambridge University Press, 1984, Seymour, L. W. CRC Crit. Rev. Ther. Drug Carrier Sys. (1992), 9, 135-187; Maeda, H.; Matsumura, Y. CRC Crit. Rev. Ther. Drug Carrier Sys. (1989), 6, 193-210). The present invention comprises human serum transferrin and serum albumin as carrier proteins, of which the accumulation in the tumor tissue is documented (Ward, S. G. Taylor, R. C.: 1-54, in Metal-Based Drugs (Gielen, M. F. (Ed.)), Freund Publishing House Ltd, 1988; Sinn, H., Schrenk, H. H., Friedrich, A., Schilling, U. and Maier-Borst, W. (1990), Nucl. Med Biol. Vol. 17(8), 819-827) as well as polyethylene glycols (PEGs) as carriers of cytostatic compounds (Topchieva, I. N. (1990), Polym. Sci. USSR 32, 833-851; Poly(ethylene glycol) Chemistry: Biotechnical and Biomedical Applications (1992), Ed. J. M. Harris, Plenum Press, New York). PEGs are, due to their bio-compatibility, their good water-solubility and synthetic divergence, very suitable for the development of therapeutic polymer conjugates. In recent years, PEGs have been conjugated mainly with medically significant proteins and enzymes (Overview in Topchieva, I. N. (1990), Polym. Sci. USSR, 32, 833-851). The production of chemoimmuno-conjugates and conjugates of proteins or of polymers occurs generally either through direct coupling of carrier substance and active substance or with the help of spacer groups, so-called homo- or heterobifunctional reagents. Until now, mainly the method of direct coupling has been used which, however, often leads to polymeric products and not-unequivocally-defined conjugates. Recently, several chemoimmunoconjugates (European Patent Application EP 91-117535 911615, European Patent Application EP 90-109268 900516, PCT International Patent Application WO 90-CA251 900809, British (UK) Patent Application GB 83-5104 830224 and European Patent Application EP 89-102370 890210), which were produced using specific bifunctional reagents, were suggested as cytostatically effective media. Furthermore, from DE 41 22 210 A1, conjugates of tumor-active compounds with transferrin or albumin are known, wherein the tumor-active compound is activated with N-hydroxy succinimide and carbodiimide and the thus-obtained mixture is directly coupled to the carrier protein. Web site: http://www.delphion.com/details?pn=US06709679__
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Biocompatible albumin lamina and method Inventor(s): Prahl; Scott Alan (Portland, OR), Wadia; Yasmin (Houston, TX) Assignee(s): Providence Health System-oregon (seattle, Wa) Patent Number: 6,680,063 Date filed: October 6, 2000 Abstract: The present invention provides a denatured albumin lamina, useful for repairing lesions on solid visceral organs. The lamina comprises human serum albumin, formed into a thin, pliant sheet and denatured. The denatured lamina can be sterilized and stored until used. As well, it can be impregnated with a variety of bioagents. A method for repairing a lesion on a solid visceral organ includes applying an energyabsorbing proteinaceous material to a lesion site on the solid visceral organ lesion; irradiating the proteinaceous material with energy sufficient to fuse the energyabsorbing material at least partially to the lesion site; applying a biocompatible denatured albumin lamina onto the proteinaceous material on the lesion site; and irradiating the biocompatible albumin lamina and the proteinaceous material with energy sufficient to fuse the biocompatible albumin lamina to the proteinaceous material and/or the lesion site. A laser solder can be deployed beneath the lamina to aid in welding it to the organ surface using laser light energy. Excerpt(s): The invention relates generally to biological tissue welding, and more specifically to repairing a lesion to a solid visceral organ. The invention also relates to manufacturing biocompatible albumin lamina suitable for use as a scaffold or patch in the repair of tissue of a solid visceral organ. Solid visceral organs such as the liver, spleen and kidney have a soft parenchyma richly interspersed with vasculature and thinly protected by a delicate fibrous capsule with limited internal fibrous support. This structure makes such organs prone to fracture and laceration with blunt abdominal trauma. Such organs are also frequently injured following abdominal trauma. For example, the liver is the most commonly injured organ following abdominal trauma. It is the second most commonly injured following blunt injuries and the third most commonly injured in penetrating injuries. Surgery of solid visceral organs like liver, spleen and kidney have always proved to be challenging, as these organs bleed profusely if traumatized and hold sutures rather poorly. Exsanguinating hemorrhage remains a significant cause of immediate mortality. A 3 cm parenchymal depth laceration has a 19% mortality and a parenchymal disruption involving 25-50% of a hepatic lobe has 28% mortality. Web site: http://www.delphion.com/details?pn=US06680063__
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Booster for therapy of disease with ultrasound and pharmaceutical IDLIQU composition containing the same Inventor(s): Tachibana; Katsuro (Fukuoka, JP), Tachibana; Shunro (Fukuoka, JP) Assignee(s): Ekos Corporation (bothell, Wa) Patent Number: 6,585,678 Date filed: August 16, 1999 Abstract: A booster comprising a plurality of microbubbles of a gas in a liquid, e.g. about 4.times.10.sup.7 cells/ml of microbubbles of a gas having a diameter of 0.1. to 100.mu.m in a 3 to 5% human serum albumin solution, and a pharmaceutical liquid
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composition comprising the booster as set forth above and a medicament, which are useful for the therapy of various diseases together with exposure of ultrasonic, where the therapeutic effects of the medicament is enhanced by the application of ultrasound in the presence of the booster. Excerpt(s): This invention relates to a booster useful for enhancing the effects of ultrasound in the therapy of various diseases and a pharmaceutical liquid composition containing the booster and a medicament which shows enhanced diffusion and penetration of the medicament into the body by applying ultrasound. More particularly, it relates to a booster useful for therapy of various disease by applying ultrasound which comprises a plurality of microbubbles of a gas in a liquid, a pharmaceutical liquid composition comprising a plurality of microbubbles of a gas and a medicament in a liquid, and the user thereof in the therapy of various diseases while applying ultrasound. It is known that various diseases are remedied by the aid of ultrasonic vibration. For example, it is described in Japanese Patent First Publication (Kokai) No. 115591/1977, etc. that percutaneous absorption of a medicament is enhanced by applying an ultrasonic vibration. Japanese Patent First Publication (Kokai) No. 180275/1990 discloses a drug-injecting device which is effective on the diffusion and penetration of the drug by applying an ultrasonic vibration in the step of injecting a drug into a human body via a catheter or a drug-injecting tube. U.S. Pat. Nos. 4,953,565 and 5,007,438 also disclose the technique of percutaneous absorption of medicaments by the aid of ultrasonic vibration. It is also reported that a tumor can be remedied by concentratedly applying ultrasound from outside the body. In order to enhance the therapeutic effects with ultrasound, it is required to apply a high energy ultrasonic vibration. However, ultrasonic vibration at an energy that is too high causes disadvantageously burns or unnecessary heat at the portion other than the desired portion. On the other hand, when the energy of an ultrasonic vibration is lowered for eliminating such disadvantages, there is a problem of less effect of the ultrasound at the desired portion. Web site: http://www.delphion.com/details?pn=US06585678__ •
Complex of DNA and microparticle of defatted lipid-binding protein for gene therapy Inventor(s): Harris; Roy (Nottingham, GB), Osborne; Nicholas David (Nottingham, GB) Assignee(s): Quadrant Healthcare, Ltd. (gb) Patent Number: 6,495,527 Date filed: January 22, 1999 Abstract: Removal of lipid from lipid-bound protein such as human serum albumin to produce defatted protein enhances ability of the protein to bind therapeutic agents for use as a carrier for the therapeutic agent. The defatted protein may be reloaded with cationic and/or anionic lipids such as fatty acids, e.g. DC-Chol, to modify charge, hydrophilicity or hydrophobicity of the defatted protein to further enhance ability of the defatted protein to bind a therapeutic agent. A reloaded lipid itself may be a therapeutic agent. The defatted protein may be produced as microparticles by spray-drying. Defatting can be achieved by removing fatty acids with acidified activated charcoal, or by solvent extraction. A complex of DNA and a microparticle of defatted protein containing a cationic or anionic lipid molecule can be used for gene therapy. Defatted albumin may be reloaded with aminocaprylic acid to provide a microparticle for binding DNA for parenteral delivery. Microparticles of defatted protein having a
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modified predetermined fatty acid profile may be used as an enhanced ultrasound contrast agent. Excerpt(s): This invention relates to lipid-binding proteins such as defatted albumin, especially as a spray-dried product, and to their therapeutic and diagnostic use. More particularly, the invention relates to microparticles that can be used as carriers in therapy, e.g. gene therapy, and to the combination of carrier and therapeutic agent. Human serum albumin (HSA) is a protein whose production in the form of microparticles having a size suitable for use in therapy by parenteral administration or by inhalation, alone or as a carrier for an active agent, e.g. in a metered dose inhaler, is disclosed in WO-A-9609814 and in WO-A-9618388. The HSA may be used as such or as a carrier for a desired active agent, since appropriate spray-drying conditions do not denature the protein or essentially reduce the existence of groups available for binding. As described in WO-A-9218164, albumin microparticles may be produced in soluble form and then stabilised, for use as diagnostic agents. WO-A-9618388 discloses that such products can be conjugated to therapeutic agents. WO-9609814 discloses that the soluble microparticles are not denaturated, and therefore retain therapeutic utility. Web site: http://www.delphion.com/details?pn=US06495527__ •
Complexes of immunogens derived from RSV surface glycoprotein G covalently coupled to a support molecule Inventor(s): Andreoni; Christine (Nantua, FR), Binz; Hans (Beaumont, FR), Nguyen; Thien Ngoc (St Julien en Genevois, FR), Nygren; Ake Per (Skarpnack, SE), Stahl; Stefan (Stockholm, SE), Uhlen; Mathias (Stockholm, SE) Assignee(s): Pierre Fabre Medicament (boulogne, Fr) Patent Number: 6,558,673 Date filed: July 27, 2000 Abstract: A complex of an immunogen and a support molecule, characterized in that the immunogen is coupled covalently to a support molecule, wherein the support molecule is a polypeptide fragment which is able to bind specifically to mammalian serum albumin is disclosed. The invention also relates to the use of such complexes to treat RSV infection, as well as vaccines derived from such complexes. Excerpt(s): In temperate countries, the RSV epidemic occurs during the winter period from November to April, and the highest incidence of serious diseases is found in the unweaned infant of 2 to 6 months. A distinction is made between two types of RSV, RSV-A and RSV-B, on the basis of the antigenic variation of the G glycoprotein of RSV: subgroup A and subgroup B, which circulate concurrently. A recent study which was carried out in France from 1982 to 1990 demonstrated the alternation of one subgroup with the other over a period of 5 years. Strain A is often the cause of infections which are more serious than those caused by strain B. In the 1960's, an unsuccessful attempt was made to develop conventional vaccines, that is using formolinactivated RSV, in analogy with anti-measles vaccines. Instead of conferring protection on the vaccinated infant, this type of vaccine had the effect of potentiating the natural viral disease. Human RSV belongs to the genus pneumovirus, which is a member of the Paramyxoviridae family. The genome of the virus consists of an RNA strand which is of negative polarity, is nonsegmented and encodes 10 distinct proteins: NS1, NS2, N, P, M, SH (or 1A), G, F, M2 (or 22K) and L. Web site: http://www.delphion.com/details?pn=US06558673__
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Compositions comprising a M-MLV reverse transcriptase and a DNA polymerase and use thereof Inventor(s): Lee; Jun E. (North Potomac, MD), Rashtchian; Ayoub (Gaithersburg, MD) Assignee(s): Invitrogen Corporation (carlsbad, Ca) Patent Number: 6,495,350 Date filed: December 23, 1999 Abstract: The present invention is directed to compositions and methods useful for the amplification of nucleic acid molecules by reverse transcriptase-polymerase chain reaction (RT-PCR). Specifically, the invention provides compositions and methods for the amplification of nucleic acid molecules in a simplified one- or two-step RT-PCR procedure using combinations of reverse transcriptase and thermostable DNA polymerase enzymes in conjunction with sulfur-containing molecules or acetatecontaining molecules (or combinations of such sulfur-containing molecules and acetatecontaining molecules), and optionally bovine serum albumin. The invention thus facilitates the rapid and efficient amplification of nucleic acid molecules and the detection and quantitation of RNA molecules. The invention also is useful in the rapid production and amplification of cDNAs which may be used for a variety of industrial, medical and forensic purposes. Excerpt(s): The present invention is in the fields of molecular and cellular biology. The invention is particularly directed to compositions and methods useful for the amplification of nucleic acid molecules by reverse transcriptase-polymerase chain reaction (RT-PCR). Specifically, the invention provides compositions and methods for the amplification of nucleic acid molecules in a simplified one- or two-step RT-PCR procedure using combinations of reverse transcriptase and thermostable DNA polymerase enzymes in conjunction with sulfur-containing molecules or acetatecontaining molecules (or combinations of sulfur-containing molecules and acetatecontaining molecules) and optionally bovine serum albumin. The invention thus facilitates the rapid and efficient amplification of nucleic acid molecules and the detection and quantitation of RNA molecules. The invention also is useful in the rapid production and amplification of cDNAs (single-stranded and double-stranded) which may be used for a variety of industrial, medical and forensic purposes. The term "reverse transcriptase" describes a class of polymerases characterized as RNAdependent DNA polymerases. All known reverse transcriptases require a primer to synthesize a DNA transcript from an RNA template. Historically, reverse transcriptase has been used primarily to transcribe mRNA into cDNA which can then be cloned into a vector for further manipulation. Avian myoblastosis virus (AMV) reverse transcriptase was the first widely used RNA-dependent DNA polymerase (Verma, Biochim. Biophys. Acta 473:1 (1977)). The enzyme has 5'-3' RNA-directed DNA polymerase activity, 5'-3' DNA-directed DNA polymerase activity, and RNase H activity. RNase H is a processive 5' and 3' ribonuclease specific for the RNA strand for RNA-DNA hybrids (Perbal, A Practical Guide to Molecular Cloning, New York: Wiley & Sons (1984)). Errors in transcription cannot be corrected by reverse transcriptase because known viral reverse transcriptases lack the 3'.fwdarw.5' exonuclease activity necessary for proofreading (Saunders and Saunders, Microbial Genetics Applied to Biotechnology, London: Croom Helm (1987)). A detailed study of the activity of AMV reverse transcriptase and its associated RNase H activity has been presented by Berger et al., Biochemistry 22:23652372 (1983). Web site: http://www.delphion.com/details?pn=US06495350__
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Dried blood factor composition comprising trehalose Inventor(s): Roser; Bruce Joseph (Cambridgeshire, GB) Assignee(s): Quadrant Drug Delivery Limited (gb) Patent Number: 6,649,386 Date filed: October 30, 1998 Abstract: A stable blood factor composition contains a stabilising amount of trehalose in the absence of human serum albumin to provide a product stable at up to 60.degree. C. Excerpt(s): This invention relates to dried compositions of blood factors for reconstitution with water or aqueous solutions. Blood factors, particularly factor VIII and factor IX, are now the standard treatment for diseases caused by a lack of the appropriate factor, in particular haemophilia. The blood factor has generally been derived from human blood by various extraction techniques, for example as disclosed in EP-A-0083483, or by expression in genetically modified micro-organisms, for example as disclosed in EP-A-0160457 and EP-A-0182448. Blood factor products such as factor VIII are highly delicate, unstable proteins. They are usually supplied in the form of frozen solutions in an appropriate buffer or, more generally, as freeze-dried powders. Even the freeze-dried powders must be kept cold during storage. In order to stabilise the freezedried material, commercial products contain a stabilising protein, in particular human serum albumin (HSA). It has not been thought possible to prepare a dry blood factor composition which is stable at ambient temperatures and at pasteurisation temperatures (e.g. 60.degree. C.) in the absence of HSA. However, the presence of HSA introduces considerable problems of purification since it is essential that the protein is free of viral contamination. The use of recombinant HSA to overcome these problems is expensive. Web site: http://www.delphion.com/details?pn=US06649386__
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Erythropoietin analog-human serum albumin fusion Inventor(s): Krane; Ian (Westborough, MA), Meade; Harry (Newton, MA), Young; Michael (Weston, MA) Assignee(s): Genzyme Transgenics Corporation (framingham, Ma) Patent Number: 6,548,653 Date filed: June 15, 1999 Abstract: Erythropoietin analog-human serum albumin (EPOa-hSA) fusion protein and methods of making and using the fusion protein. Excerpt(s): The invention relates to erythropoiein analog-human serum albumin (EPOahSA) fusion proteins, nucleic acids which encode EPOa-hSA fusion proteins, and methods of making and using EPOa-hSA fusion proteins and nucleic acids. In general, the invention features, an EPOa-hSA fusion protein, wherein at least one amino acid residue of the EPOa moiety of the fusion protein is altered such that a site which serves as a site for glycosylation in erythropoietin (EPO) does not serve as a site for glycosylation in the EPOa, e.g., an EPOa-hSA fusion protein in which at least one amino acid residue which can serve as a glycosylation site in erythropoietin is altered, e.g., by substitution or deletion, such that it does not serve as a glycosylation site. In a preferred embodiment, the EPOa-hSA fusion protein has the formula: R1-L-R2; R2-L-R1; or R1-LR2-L-R1, wherein R1 is an EPOa amino acid sequence, L is a peptide linker and R2 is
Patents 169
human serum albumin amino acid sequence. Preferably, R1 and R2 are covalently linked via the peptide linker. Web site: http://www.delphion.com/details?pn=US06548653__ •
Hollow fiber membrane made of an ethylene-vinyl alcohol polymer Inventor(s): Kakiuchi; Tomoki (Kurashiki, JP), Matsumoto; Yoichi (Kurashiki, JP), Nakaji; Shuhei (Kurashiki, JP), Sekiguchi; Koji (Kurashiki, JP), Suehiro; Takeshi (Kurashiki, JP), Sugo; Nozomu (Kurashiki, JP), Takai; Masato (Kurashiki, JP), Tsuruta; Hitoshi (Kurashiki, JP) Assignee(s): Kuraray Co., Ltd. (kurashiki, Jp) Patent Number: 6,514,409 Date filed: January 10, 2001 Abstract: A hollow fiber membrane made of an ethylene-vinyl alcohol polymer, comprises a dense layer existing in the inner surface and a porous layer existing in the layer other than the dense layer, wherein the hollow fiber membrane has a porosity of 60 to 90%, an overall mass transfer coefficient for myoglobin in a water-based system of not less than 0.003 cm/min., and a rejection rate for albumin in a bovine blood system of not less than 97%. The EVA hollow fiber membrane is useful for hemopurification membranes such as hemodialysis membranes, hemodiafiltration membranes, hemofiltration membranes and continuous hemofiltration membranes, and a process for producing the same. Excerpt(s): The present invention relates to a hollow fiber membrane made of an ethylene-vinyl alcohol polymer (hereinafter the term "ethylene-vinyl alcohol" is simply referred to as "EVA," and the term "hollow fiber membrane made of an EVA polymer" is simply referred to as "EVA hollow fiber membrane"), and a process for producing the hollow fiber membrane. More particularly, the present invention related to an EVA hollow fiber membrane used for hemopurificafion membranes such as hemodialysis membranes, hemodiafiltration membranes, hemofiltration membranes and continuous hemofiltration membranes, and a process for producing the same. Hollow fiber membranes made of an EVA polymer have been widely used in applications for various separation membranes for industrial, medical and other purposes since the hollow fiber membranes are excellent in hydrophilicity (see Japanese Patent Laid-Open No. Hei 542208). Especially, the hollow fiber membranes are excellent in biocompatibility and chemical stability, and have very little eluted substances, so that the hollow fiber membranes have been widely used for medical applications. Their representative uses include, for instance, hemodialysis filtration membranes. Japanese Examined Patent Publication No. Sho 58-36602, Japanese Patent Laid-Open Nos. Sho 58-45239 and Hei 542208, and the like disclose membranes having an asymmetric structure comprising a dense layer in the inner surface predominantly imparting fractionalization and permeability, and a porous layer supporting the dense layer as an EVA hollow fiber membrane having both high permeability and high fractionalization. Web site: http://www.delphion.com/details?pn=US06514409__
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Intra-serum and intra-gel for modeling human skin tissue Inventor(s): Blank; Thomas B. (Chandler, AZ), Hazen; Kevin H. (Gilbert, AZ), Lorenz; Alexander D. (Phoenix, AZ), Malin; Stephen F. (Phoenix, AZ), Ruchti; Timothy L. (Gilbert, AZ), Thennadil; Suresh (Tempe, AZ), Troy; Tamara L. (Chandler, AZ), Welch; James Matthew (Tempe, AZ) Assignee(s): Instrumentation Metrics, Inc. (chandler, Az) Patent Number: 6,475,800 Date filed: February 10, 2000 Abstract: The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with lecithin acting as the emulsifier. These solutions that have varying particle sizes may be spiked with basis set components (albumin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds such as collagen, elastin, globulin and bilirubin may be added, as can salts such as Na.sup.+, K.sup.+ and Cl.sup.-. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen (gelatin). The resulting samples are flexible in each analyte's concentration and match the skin layers of the body in terms of the samples reduced scattering and absorption coefficients,.mu.m.sub.s and.mu.m.sub.a. This family of samples is provided for use in the medical field where lasers and spectroscopy based analyzers are used in treatment of the body. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm-.sup.1). Excerpt(s): The invention relates to noninvasive spectroscopy. More particularly, the invention relates to the modeling of human tissue for use in noninvasive spectroscopy. In the field of noninvasive spectroscopy, photons generated by a source penetrate into the body of a subject, interact with the subject's tissue layers and exit to a detector. The interaction with the tissue layers is complex and is not well understood. Models that simulate the tissue may be utilized to address such fundamental questions as the net analyte signal, depth of penetration of the photons and radial diffusion of the photons. Knowledge of the exact chemical composition of a tissue surrogate will allow chemical and physical interpretation of spectra obtained on human skin where the exact chemical composition of the sample is unknown. For these reasons, a model of skin tissue samples would be beneficial. The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with emulsifiers such as lecithin used to keep the solution from separating. These emulsions have oil droplets with varying particle sizes acting as scatterers and may be spiked with basis set components (e.g. albumin, globulin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds, such as collagen, elastin, globulin, lactic acid and bilirubin may be added, as can salts such as Na.sup.+, K.sup.+ and Cl.sup.-. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen. The resulting samples are flexible in that each analyte's concentration may be adjusted independently of the others and that each skin layer of the body may be
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matched in terms of the samples' coefficients,.mu.'.sub.s and.mu.sub.a.
reduced
scattering
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Knockout animals Inventor(s): Kohno; Kenji (Nara, JP) Assignee(s): Dnavec Research Inc. (ibaraki, Jp) Patent Number: 6,576,813 Date filed: November 18, 1999 Abstract: Transgenic mice are constructed by binding the "hHB-EGF/DTR" gene to the downstream of an albumin enhancer/promoter that is expressed specifically in hepatic parenchymal cells and introducing this unit into mice. After the "hHB-EGF/DTR" gene has been confirmed to be expressed specifically in hapatic cells, diphtehria toxin is administered to the transgenic mice to examine whether the hepatic parenchymal cells are disrupted. The hepatic cells of the transgenic mice can be selectively dirupted depending on the administration period of the diphtheria toxin. Excerpt(s): The present invention relates to a method to selectively disrupt a particular organ, tissue, or cell of an animal at a specific period, and an expression unit, vector, host cell, and kit that are utilized in the method. The invention also relates to a nonhuman animal in which a particular organ, tissue, or cell is disrupted by the method. A normal function of a tissue or cell can be clarified by deleting the tissue or cell and examining the resulting effect. This procedure is performed by, for example, surgical ablation of a tissue or cell (including laser ablation) and specific expression of a toxin in a target cell (Palmiter, R. D. et al. (1987) Cell 50, 435-443; Breitman, M. L. et al. (1987) Science 238, 1563-1565; Borrelli, E. et al. (1988) Proc. Natl. Acad. Sci. USA 85, 7572-7576; Heyman, R. A. et al. (1989) Proc. Natl. Acad. Sci. USA 86, 2698-2702; Lowell, B. B. et al. (1993) Nature 3664 740-742; Ross, S. R. et al. (1993) Genes Dev. 7, 1318-1324). When the target cells exist diffusely in the whole body, it is impossible to efficiently ablate only the target cells by the former method. When the target organ, tissue or cell is essential for normal development, the latter method results in death of the individual at embryo stage, and it is thus impossible to analyze animals after birth. Web site: http://www.delphion.com/details?pn=US06576813__
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Manufacturing process to control particle size Inventor(s): Kuczynski; Bruce (Highland Park, NJ), Narra; Rama K. (North Brunswick, NJ), Schramm; Ernst (North Brunswick, NJ), Zodda; Julius P. (Mercerville, NJ) Assignee(s): Bracco Diagnostics, Inc. (princeton, Nj) Patent Number: 6,730,286 Date filed: February 28, 2001 Abstract: A process for preparing a sterile injectable suspension of radiolabeled macroaggregated serum albumin suitable for use in scanning a mammalian patient consisting of:1) purifying serum albumin with a saline solution;2) buffering the purified serum albumin;3) adding stannous halide in HCl solution to the buffered mixture to obtain a reaction mixture;4) gradually heating and cooling the reaction mixture to form
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macroaggregate particles;5) separating the macroaggregates from the reaction mixture;6) suspending the macroaggregates in sterile water for injection;7) adding purified serum albumin;8) lyophilizing the suspension; and9) reconstituting the radiolabeled lyophilizate with 99mTc. The invention also includes a process for preparing a stable, sterile lyophilizate of macroaggregate particles of human serum albumin consisting of steps 1-7. Excerpt(s): This invention relates to a process for preparing a radiopharmaceutical diagnostic agent useful in scanning applications of organs and tissues in a mammal. More particularly, the invention relates to a sterile, stable macroaggregates of human serum albumin suspended in a highly purified, stable human serum albumin carrier in a form which is labeled with technetium-.sup.99m Tc prior to injecting the human serum albumin into a patient for diagnostic scanning of the lung. Macroaggregated particles of human serum albumin having a particle size of 3 to 150 microns in diameter radiolabeled with technetium-99m have been used in lung function studies and diagnosis. After injection into the patient, the radiolabeled macroaggregated particles diffuse into and are retained by the capillary system of the lung allowing scintigraphic visualization of the vascular system by a diagnostic practitioner. The radiolabeled macroaggregates obstruct the capillaries for only a short time and cause no harm to the pulmonary system. Subsequent to the short retention, the macroaggregates are digested by the phagocytes in the blood thereby clearing the capillaries from the macroaggregates. Technetium-99m, which emits gamma rays, has a radioactive half-life of only about 6 hours and the associated radiation disappears along with the particles of the macroaggregates from the pulmonary system. A critical characteristic in macroaggregated human serum-containing product is particle size. The product is designed for the macroaggregates to be trapped in the pulmonary capillaries. If embolisms are present in the capillary system, the macroaggregates will not travel through the blockage indicating blood circulatory problems by the lack of radiation from the area of the capillaries where the macroaggregate particles could not enter. Web site: http://www.delphion.com/details?pn=US06730286__ •
Marker useful for detection and measurement of free radical damage and method Inventor(s): Bar-Or; David (Englewood, CO), Lau; Edward (Boulder, CO) Assignee(s): Ischemia Technologies, Inc. (denver, Co) Patent Number: 6,475,743 Date filed: October 2, 1998 Abstract: The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R [SEQ ID NO:1], wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring albumin, for detection and
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quantification of the marker. Methods of the present invention also include use of the marker as a "biochemical tag," thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics. Excerpt(s): The present invention relates to a marker for detecting and measuring free radical damage; a method for the direct detection and measurement of the damaging activity of free radicals in vivo is provided. Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction, like dominoes. Their chief danger comes from the damage they can do when they react with important cellular components such as DNA, or the cell membrane. Cells may function poorly or die if this occurs. A free radical is any molecular species capable of independent existence, that contains one or more unpaired valence electrons not contributing to intramolecular bonding, and is--in that sense--"free". Free radicals are produced by oxidation/reduction reactions in which there is a transfer of only one electron at a time, or when a covalent bond is broken and one electron from each pair remains with each atom. Free radicals are highly reactive, owing to the tendency of electrons to pair--that is, to pair by the receipt of an electron from an appropriate donor or to donate an electron to an appropriate acceptor. Thus, once formed, free radicals initiate a chain reaction, like dominoes--whenever a free radical reacts with a nonradical, a chain reaction is initiated until two free radicals react and then terminate the propagation with a 2-electron bond (each radical contributing its single unpaired electron). Web site: http://www.delphion.com/details?pn=US06475743__ •
Method for detection of prostate specific membrane antigen in serum Inventor(s): Chadha; Kailash C. (Williamsville, NY), Kawinski; Elzbieta (Orchard Park, NY) Assignee(s): Health Research, Inc. (buffalo, Ny) Patent Number: 6,475,389 Date filed: May 8, 2001 Abstract: A method for detecting prostate specific membrane antigen (PSMA) in serum by immunoassay including the steps of capturing PSMA from serum using a PSMA antibody and detecting the captured PSMA with an anti-.alpha.sub.1 -antichymotrypsin antibody. In a preferred embodiment, PSMA is captured using a PSMA antibody by diluting the PSMA antibody, coating a surface such as the surface of wells in a microtiter plate, with the resulting solution, blocking non-specific sites on the surface with albumin, diluting the serum with a blocking buffer and applying a diluted sample to the surface to capture PSMA. A preferred embodiment for detecting captured PSMA, includes the steps of removing non-captured material by washing the surface, applying anti-.alpha.sub.1 antichymotrypsin antibody diluted in a blocking solution such as albumin solution and detecting bound PSMA using peroxidase labeled anti-rabbit IgG and OPD substrate. Excerpt(s): It is becoming increasingly evident that the monitoring of prostate-specific membrane antigens (PSMA) is desirable for the detection and management of prostate cancer. Prostate cancer is the most common cancer in males in the United States. The efficiency of early detection of prostate cancer has increased with a serum test for the prostate-specific antigen (PSA). However, PSA is neither tissue-specific nor disease-
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specific. Many other conditions of the prostate gland, some of them being benign, can also result in abnormal elevation of PSA level in the serum (Polascik, et al., Prostatespecific antigen: A decade of discovery--what we have learned and where we are going, J. Urol, vol 162, pp 293-306, 1999). Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with both intra and extracellular domains, and is highly specific for the prostate tissue (Israeli, et al., Molecular cloning of a complimentary DNA encoding of prostate-specific membrane antigen, Cancer Res, vol 53, pp 227-230, 1993). PSMA is expressed in benign and malignant prostatic epithelium and can be detected immunohistochemically (Horoszewicz, et al. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients, Anticancer Res, vol 7, pp 927-936, 1987; Silver, et al., Prostate-specific membrane antigen expression in normal and malignant human tissues, Clin Cancer Res, vol 3, pp 81-85, 1997; Wright, et al., Expression of prostate-specific membrane antigen (PSMA) in normal, benign, and malignant prostate tissues, Urol Oncol, vol 1, pp 18-28, 1995; Bostwick, et al., Prostatespecific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: A study of 184 cases, Cancer, vol 82, pp 2256-2261, 1998; and Sweat, et al., Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastasis, Urology, vol 52, pp 637-640, 1998). PSMA serum levels have been proposed to be of prognostic significance in prostate cancer patients with advanced disease, see e.g. Grasso, et al., Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage, Cancer Research vol 58, pp 1456-1459, 1998. Web site: http://www.delphion.com/details?pn=US06475389__ •
Method for preparing albumin hydrolysates Inventor(s): Neumuller; Waldemar (Wilhelm-Baum-Weg 29, D-37077 Gottingen, DE) Assignee(s): None Reported Patent Number: 6,555,336 Date filed: August 20, 2001 Abstract: In a method for preparing albumin hydrolysates from a starting material containing albumins in concentrated or isolated form, the starting material are homogenized with an aqueous solution at a temperature of between 10 and 80.degree. C. and at a pH of between 8 and 12 in the presence of a first protease for the enzymatic hydrolysis of the albumins. At least one further protease whose cleaving spectrum differs from that of the first protease is added after between 1 and 60 min. from the start of homogenization for the further enzymatic hydrolysis of the albumins. The proteases are inactivated by a heat treatment at a pH below 7.5 within between 1 and 60 minutes from addition of the last protease. The non-hydrolyzed albumins are precipitated at a pH below 7.5. The precipitated non-hydrolyzed albumins are separated from the albumin hydrolysates contained in the solution; and the albumin hydrolysates contained in the solution are concentrated. Excerpt(s): The invention relates to a method for preparing albumin hydrolysates from a starting material containing albumin in concentrated of isolated form. Albumin hydrolysates are albumin fragments of different lengths, which may be produced by chemical hydrolysis by means of alkali or acid or by enzymatic hydrolysis. In the chemical hydrolysis protein damages like lysinoalanine and chloropropanol may occur as a drawback. Known disadvantages of the enzymatic hydrolysis are long hydrolysis times and bitter peptides. Further, the albumin yield in relation to the albumin input is
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clearly smaller with enzymatic hydrolysis than with chemical hydrolysis. On the other hand, the chemical hydrolysis takes place more or less non-specifically. In weighing up all factors, the enzymatic hydrolysis is presently preferred for preparing albumin hydrolysates for the food and pharmaceutics sectors. Prior art methods for preparing albumin hydrolysates from a starting material containing albumin in concentrated or isolated form by means of enzymatic hydrolysis generally have a similar structure, the albumin, as a rule being dissolved before or after the enzymatic hydrolysis at an alkaline pH. Web site: http://www.delphion.com/details?pn=US06555336__ •
Method for the prediction of preeclampsia and other diseases Inventor(s): Arbogast; Bradley W. (Johnson City, TN) Assignee(s): Arbogast Pharmaceuticals, Inc. (johnson City, Tn) Patent Number: 6,642,055 Date filed: March 31, 2000 Abstract: The invention disclosed is a process for determining the cytoprotective activity of plasma that prevents the destruction of endothelial cells and forestalls the development of a number of diseases such as atherosclerosis, preeclampsia, edema, nephrotic syndrome, and stroke. The present invention includes a method of diagnosing a patient's proclivity to develop a disease having a correlation to a reduction in the concentration of pI 5.6 albumin in the plasma by determining a value indicative of the concentration of the pI 5.6 albumin that is not bound to VLDL ("free pI 5.6 albumin") in the patient's blood serum. The preferred embodiment of the process utilizes in vitro methods to obtain an indicator of the free pI 5.6 albumin instead of directly measuring the concentration of the free pI 5.6 albumin. The preferred method comprises the steps of:(a) providing a plasma sample containing free albumin, triglycerides, very low density lipoproteins, low density lipoproteins, and non-esterified fatty acids bound to the free albumin;(b) determining the concentration of the free albumin;(c) determining the concentration of the non-esterified fatty acids bound to the free albumin; and(d) calculating a value indicative of the toxicity preventing ability of the plasma by comparing the concentration of the free albumin to the concentration of the nonesterified fatty acids bound to the free albumin. The present process does not provide direct measurement of the cytoprotective activity of plasma, but rather, an empirical value which has clinical relevance in identifying patients with a high chance of developing diseases inhibited by pI 5.6 albumin. Excerpt(s): The present invention relates to methods for predicting and following illnesses. More particularly, the present invention relates to the diagnosis of preeclampsia and other diseases. Vascular disease is often related to the composition of blood flowing therethrough. In particular, high concentrations of very low density lipoproteins (VLDL) in blood have a deleterious effect on vascular integrity. Very low density lipoproteins in blood tend to break down the inner vascular walls causing vascular diseases including preeclampsia, atherosclerosis, stroke, peripheral vascular disease, diabetic vascular disease, and such. Methods providing earlier detection of vascular diseases, and methods for diagnosing a patient's proclivity toward developing a vascular disease at a later point in his life are desirable so that such disease may be better controlled, or even avoided. The early detection of preeclampsia is particularly important.
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Web site: http://www.delphion.com/details?pn=US06642055__ •
Method for the removal/purification of serum albumins and means for use in the method Inventor(s): Johansson; Hans (Summit, NJ) Assignee(s): Amersham Biosciences AB (uppsala, Se) Patent Number: 6,613,884 Date filed: February 15, 2001 Abstract: A method for removing a serum albumin from a mixture of other compounds by contacting said mixture with a ligand a) having affinity for and enabling selective binding of the serum albumin and b) being attached to a base matrix insoluble in the aqueous media used or being possible to attach to such a matrix after having become bound to the serum albumin, characterized in that said ligand is derived from an albumin binding bacterial cell surface receptor and that the ligand lacks the IgG-binding and/or.alpha.sub.2 -macroglobulin-binding ability found in native forms of these type of bacterial receptors. An albumin-binding ligand derived from a cell surface bacterial receptor and attached covalently to a carrier matrix, characterized in that the ligand is monovalent with respect to ability to bind a serum albumin. A method for removal of serum albumin from a sample that is to be assayed for non-serum albumin components. The characteristic feature is to subject the sample to affinity adsorption by an albumin-binding ligand derived from an albumin-binding receptor. Excerpt(s): The present invention concerns a method for the separation/removal of a mammalian serum albumin from a solution containing a mixture of proteins in order to obtain a solution/preparation that is substantially devoid of the serum albumin. The invention also concerns novel immobilized forms of albumin-binding ligands deriving from native forms of bacterial receptors that are able to bind to one or more serum albumins. For a long time there has been a large demand for mammalian serum albumins, for instance serum albumin of human or bovine origin (HSA and BSA, respectively). For HSA this has mainly depended on its therapeutic use as a plasma volume expander. Originally serum albumins were obtained from sera/plasma of the appropriate species origin. For some years the focus has been to produce serum albumins recombinantly, in particular HSA. For bacterially produced recombinant forms, it has become urgent to remove host cell contaminants because they may be hazardous in vivo to mammals. For some time it has become apparent that producing HSA in transgenic animals should be beneficial, for instance in transgenic cows. This latter alternative, however, has the drawback that HSA will be present in mixture with the HSA analogue of the host animal (for instance with BSA if HSA produced in cows). This has created novel purification problems, for instance the specific removal of BSA from HSA. Serum albumin preparations intended for use in vivo shall according to accepted practice contain<0,01%, such as<0,001% proteins that are heterologous to the species to which the preparation is to be administered. HSA preparations, for instance, that are to be used in humans shall contain<0,01%, such as<0,001% BSA. All percentages are w/w. Web site: http://www.delphion.com/details?pn=US06613884__
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Method for the treatment of solid tumors by albumin microparticles incorporating paclitaxel Inventor(s): Falciani; Marco (Milan, IT) Assignee(s): Acs Dobfar S.p.a. (tribiano, It) Patent Number: 6,652,884 Date filed: April 17, 2001 Abstract: The invention concerns a method for the treatment of tumors sensitive to Paclitaxel, by intra-arterial injections of dispersions of microparticles of albumin incorporating Paclitaxel in physiological solutions. Excerpt(s): The invention relates to a method for the treatment of tumors sensitive to Paclitaxel, and more particularly concerns a method by which a significant remission or cure of the tumor, with very low toxic side effects, can be achieved by just a few infusions, each of short duration and spaced apart by some weeks. Paclitaxel is a substance well known in the literature, with important clinical activity on a large number of tumors, such as ovary, lung, head and neck, bladder and breast tumors. Paclitaxel is insoluble in water. In order to render it soluble and suitable for intravenous administration, it has been mixed with a surfactant (such as polyethoxylated castor oil, known by the registered name "Cremophor EL") and with about 50% of anhydrous alcohol USP, as vehicles for the Paclitaxel: this mixture was patented by Bristol-Myers Squibb and is known by the registered name "Taxol" to which reference will be made hereinafter, for simplicity. The presence of the surfactant and the anhydrous alcohol has serious drawbacks, such as strong hypersensitivity, in addition to other side effects. Web site: http://www.delphion.com/details?pn=US06652884__
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Microencapsulated compounds and method of preparing same Inventor(s): D'Souza; Martin J. (Sugar Hill, GA) Assignee(s): The Corporation of Mercer University (macon, Ga) Patent Number: 6,555,110 Date filed: May 4, 1995 Abstract: Compositions useful in treating immune modulated disease comprising an anticytokine antibody or immune active drug capable of modifying cytokine activity or modulating the immune system microencapsulated with a biodegradable nonantigenic material, such as albumin or PLGA. When the composition is introduced into a subject, it is phagocytosed by the target organ, the target organ digests the microsphere, releasing the drug or an active form or fragment thereof intracellularly. The drug then modifies the target organ function, thereby modulating it's activity. A method is disclosed for preparation of the microencapsulated composition. Excerpt(s): The present invention relates generally to the field of drug delivery systems. More particularly, the present invention relates to a method for microencapsulating drugs using biodegradable nonantigenic materials and also to microencapsulated compositions that are targeted either to macrophages, other phagocytic cells of the immune system, or a diseased organ, which phagocytize the microspheres and digest the coating, releasing the intact drug or active fragment thereof intracellularly or at the site of attachment Such compositions are useful in treating and preventing disease. Drug delivery technology can bestow new leases on the lives of seemingly ineffective or
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inefficient drugs by targeting them specifically to sites of action. In this manner, unwanted systemic side effects are obviated and dose requirements are substantially reduced. Macrophage mediated delivery of drugs has been suggested as an alternative for treatment of several types of diseases. Modern immunology has acknowledged the importance of the monocyte and its mature counterpart, the macrophage as the prime antigen presenting cell in immune interactions. As an extension of this function it can be theorized that macrophages may be utilized to present immunoactive drugs to relevant components of the immune system such as lymphocytes in an effort to modulate their function. Systemic elimination systems developed by the body to attack and eliminate foreign material include macrophages and Kupffer cells. For the purposes of the present invention the term macrophage includes Kupffer cells, when appropriate. Macrophages are cells widely distributed in many tissues of the body including lympho-hemopoietic organs, skin, gut, other portals of entry and the nervous system. They are found in direct contact with the blood (monocytes, sinus-lining Kupffer cells) or extravascular space, and undergo complex migrations as they enter tissues after production mainly within the bone marrow of the adult. As mobile and long-lived cells the mononuclear phagocytes play central roles as effector cells in inflammatory reactions and cell mediated immune responses. Monocytes produced in the bone marrow are released into the blood stream where they circulate with an estimated half life of 8-9 hours. Most experimental evidence indicates that the monocytes migrate into tissue to replace senescent tissue macrophages, and differentiate into cells of varied morphological and functional characteristics. Although definitive information on density and tissue distribution of these cells is still not available it is clear that the tissue content of mononuclear phagocytes, often associated with the vasculature greatly exceeds the bone marrow replicative pool. These cells, in a real sense are the first line of defense, followed by secondary waves of granulocytes, lymphocytes and monocytes from the circulation. Web site: http://www.delphion.com/details?pn=US06555110__ •
PCR reaction mixture for fluorescence-based gene expression and gene mutation analyses Inventor(s): Borlak; Jurgen (Lehrte OT Immensen, DE), Thum; Thomas (Hannover, DE) Assignee(s): Fraunhofer-gesellschaft Zur Forderung Der Angewandten Forshung E.v. (munich, De) Patent Number: 6,558,929 Date filed: January 3, 2001 Abstract: An increase in the selectivity, sensitivity and the suppression of primer dimer formations, fluorescence-based gene expression analyses and gene mutation analyses is accomplished by adding bovine serum albumin to the conventional PCR reaction components. Magnesium chloride concentration is adjusted accurately depending on the Taq polymerase used. Excerpt(s): Gene expression occupies a key function in the evaluation of molecular processes in the body and great efforts are being made to investigate the significance of the expression of numerous genes also as a result of drug effects and to check it with respect to its predictive value in regard to the course of an illness and the success of a therapy. A prerequisite for converting genetic information initially is the transcribing of the corresponding DNA sequence into mRNA. Gene expression can be regulated at the level of transcription as well as post-transcriptionally. For evidence-based medicine, the clarification of the mechanisms, which lead to a changed gene expression in the course
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of an illness, is an important objective, because new therapy concepts can be derived from it, which lead to an improved treatment of patients. According to estimates of the organizers, the human genome project presumably will come to a conclusion in the year 2001. At the end of this project, which is being conducted worldwide, approximately 140,000 genes will have been identified. The analysis of the gene expression in different cell types and tissues, which provides important information concerning the normal state and the genesis of the pathologic state of cells and tissues, represents the greatest challenge at the present time as well as in the post-genome epoch. Web site: http://www.delphion.com/details?pn=US06558929__ •
Preparation of diagnostic agents Inventor(s): Heath; David (The Park, GB), Johnson; Richard A. (West Bridgford, GB), Senior; Peter J. (Near Melbourne, GB), Sutton; Andrew D. (Ruddington, GB) Assignee(s): Quadrant Healthcare (uk) Limited (nottingham, Gb) Patent Number: 6,569,405 Date filed: September 28, 1999 Abstract: Microcapsules are prepared by a process comprising the steps of (i) spraydrying a solution or dispersion of a wall-forming material in order to obtain intermediate microcapsules and (ii) reducing the water-solubility of at least the outside of the intermediate microcapsules. Suitable wall-forming materials include proteins such as albumin and gelatin. The microcapsules have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilization and cross-linking of the wall-forming material allows novel microsphere preparations to be produced. Excerpt(s): The present invention relates to the preparation of diagnostic agents comprising hollow proteinaceous microcapsules used to enhance ultrasound imaging. The fact that air bubbles in the body can be used for echocardiography has been known for some time. Bubble-containing liquids can be injected into the bloodstream for this purpose (see Ophir et al (1980) "Ultrasonic Imaging" 2, 67-77, who stabilised bubbles in a collagen membrane, U.S. Pat. No. 4,446,442 (Schering) and EP-A-131 540 (Schering)) and EP-A-224934 and EP-A-324938 disclose the use of bubbles prepared by sonicating an albumin solution. However, the size distribution of the bubbles is apparently uncontrollable and the bubbles disappear when subjected to pressure experienced in the left ventricle (Shapiro et al (1990) J. Am. Coll. Cardiology, 16(7), 1603-1607). We have found that a process of atomising a solution of microcapsule-forming agent and then insolubilising the microcapsules which are formed leads to an improved product. Przyborowski et al (1982 Eur. J. Nucl. Med. 7, 71-72) disclosed the preparation of human serum albumin (HSA) microspheres by spray-drying for radiolabelling and subsequent use in scintigraphic imaging of the lung. The microspheres were not said to be hollow and, in our repetition of the work, only solid microspheres are produced. Unless the particles are hollow, they are unsuitable for echocardiography. Furthermore, the microspheres were prepared in a one step process which we have found to be unsuitable for preparing microcapsules suitable for echocardiography; it was necessary in the prior process to remove undenatured albumin from the microspheres (which is not necessary in our process); and a wide size range of microspheres was apparently obtained, as a further sieving step was necessary. Hence, not only was the Przyborowski et al process not an obvious one to choose for the preparation of microcapsules useful in
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ultrasonic imaging but the particles produced were unsuitable for that purpose. We have devised a considerable improvement over that prior process. Web site: http://www.delphion.com/details?pn=US06569405__ •
Preparing monomeric metal ion chelator containing diacetyl glycine group linked to proteinaceous molecule Inventor(s): Savage; M. Dean (Rockford, IL), Sykaluk; Laura L. (Rockford, IL) Assignee(s): Pierce Biotechnology, Inc. (rockford, Il) Patent Number: 6,670,159 Date filed: July 25, 2001 Abstract: A precursor for the construction of chelated metal conjugates which demonstrate improved assay performance and utility in minimizing non-specific binding while maintaining specificity for target molecules is disclosed. The precursor has tridentate functionality towards multivalent ions such as iron and nickel and contains a diacetyl glycine group covalently linked via an amide to a molecule such as a proteinaceous molecule providing a primary amide group for amide bond formation. The precursor is preferably prepared in monomeric form by reacting nitrilotriacetic acid or a salt thereof in an aqueous medium at an alkaline pH of at least 8 with a proteinaceous molecule containing a primary amine group in the presence of a carbodiimide. The proteinaceous molecule may be bovine serum albumin or an enzyme such as alkaline phosphatase or horseradish peroxidase. Excerpt(s): The present inventions relates to metal ion affinity interactions with target molecules and, more particularly, to improvements thereof whereby non-specific interactions with non-target molecules can be diminished. Affinity binding interaction based on the used of a chelated metal have been widely used due to the propensity of certain metals to preferably bind to given functional groups on target molecules such as proteins, peptides, and like compounds. Immobilized metal-ion chromatography, for example, has been used with a variety of different metals. Phosphorylated target molecules have been purified using columns containing immobilized ferric ions. Polyhistidine tagged fusion proteins nave been purified using columns containing immobilized divalent nickel. Peroxidase and biotin probes containing chelated metals have also been used for polyhistidine tagged fusion protein detection and in connection with immunoassays. It is recognized that in metal-ion chromatography, the chelating functionality used to immobilize the metal to construct the chelator-metal conjugate is important. With iron, iminodiacetic acid functionality has been used due to its tight binding characteristics with ferric ions. With nickel, as well with many other less used metal ions, the nitrilotriacetic acid tetradentate functionality has been used in both column and probe formats due to its tight binding characteristics with these metal ions. Web site: http://www.delphion.com/details?pn=US06670159__
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Process for purifying recombinant human serum albumin Inventor(s): Noda; Munehiro (Osaka, JP), Ohmura; Takao (Osaka, JP), Sumi; Akinori (Osaka, JP), Yokoyama; Kazumasa (Osaka, JP) Assignee(s): Mitsubishi Pharma Corporation (tokyo, Jp) Patent Number: 6,617,133 Date filed: May 24, 1999 Abstract: The invention provides a process for purifying recombinant human serum albumin (rHSA) by heating a-culture medium containing rHSA and the rHSAproducing host cells, feeding said heated solution upwardly into a fluidized bed in which adsorbent particles are suspended to effect contacting with the adsorbent particles and then recovering the adsorbed fraction containing the rHSA, and a composition comprising rHSA which shows a A350/A280 ratio of below 0.015, when formulated into a 25% solution of said albumin. Excerpt(s): This invention relates to a process for easily purifying human serum albumin obtained in high yields by gene manipulation. The present invention also relates to a composition comprising recombinant human serum albumin which shows an extremely low degree of coloring, which is a serious problem characteristic to recombinant human serum albumin. Human serum albumin (hereinafter referred to simply as HSA) is the most abundant protein contained in plasma. It contributes to the maintenance of osmotic pressure in blood and binds to nutrients and metabolites to thereby transport these substances. HSA having these functions has been employed as a drug for treating hypoalbuminemia caused by an albumin loss or reduction in albumin synthesis, and in hemorrhagic shock. Under these circumstances, techniques for the mass production and purification of HSA by means of gene manipulation (as a substitute for the HSA originating in blood) have been developed as recombinant DNA technology has progressed. Web site: http://www.delphion.com/details?pn=US06617133__
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Propagation of human hepatocytes in non-human mammals Inventor(s): Wu; Catherine H (Avon, CT), Wu; George Y. (Avon, CT) Assignee(s): The University of Connecticut (farmington, Ct) Patent Number: 6,525,242 Date filed: November 2, 1999 Abstract: The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. Excerpt(s): The present invention relates to the propagation of human hepatocytes in the livers of non-human animals that have been tolerized to the human cells. Such animals provide an in vivo model system of the human liver that may be used in toxicology assays and in the study of human liver diseases, including the various forms of hepatitis (in particular hepatitis B and C) and alcohol-induced liver degeneration. They may also be used as a source of human hepatocytes for reconstitution of liver tissue, thereby
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providing an alternative to liver transplantation. To accurately study the physiology of human liver cells (hepatocytes), scientists need a model system in which the hepatocytes exist as they would in the intact liver. Such systems have proven to be difficult to achieve, because when hepatocytes are removed from their native environment, they tend to lose their specialized functions, or "de-differentiate". The loss of liver-specific functions makes it difficult or impossible to study the normal functions of hepatocytes as well as their response to chemical or biological agents. For example, research directed toward infectious diseases of the liver, in particular viral hepatitis, has been hampered by the lack of an adequate model system. Hepatitis B and hepatitis C, and the problems that have been encountered by scientists studying these infectious and dangerous viruses, are discussed in the following subsections. In addition, a system for propagating human hepatocytes could be used to provide cells that could be used as an alternative or adjunct to liver transplant. Currently, patients suffering from liver disease may have to wait for long periods of time before a suitable organ for transplant becomes available. After transplant, patients need to be treated with immunosuppressive agents for the duration of their lives in order to avoid rejection of the donor's liver. A method for propagating the patient's own cells could provide a source of functional liver tissue which would not require immunosuppression to remain viable. Web site: http://www.delphion.com/details?pn=US06525242__ •
Purified thermostable Pyrococcus furiosus DNA polymerase I Inventor(s): Mathur; Eric J. (Solana Beach, CA) Assignee(s): Stratagene (la Jolla, Ca) Patent Number: 6,489,150 Date filed: February 5, 1999 Abstract: Purified thermostable Pyrococcus furiosus DNA polymerase that migrates on a non-denaturing polyacrylamide gel faster than phosphorylase B and Taq polymerase and more slowly than bovine serum albumin and has an estimated molecular weight of 90,000-93,000 daltons when compared with a Taq polymerase standard assigned a molecular weight of 94,000 daltons. Excerpt(s): The present invention relates to a thermostable enzyme having DNA polymerase I activity useful in nucleic acid synthesis by primer extension reaction. The archaebacteria are a recently discovered group of microorganisms that grow optimally at temperatures above 80.degree. C. Some 20 species of these extremely thermophilic bacteria-like organisms have been isolated, mainly from shallow submarine and deep sea geothermal environments. Most of the archaebacteria are strict anaerobes and depend on the reduction of elemental sulfur for growth. The archaebacteria include a group of "hyperthermophiles" that grow optimally around 100.degree. C. These are presently represented by three distinct genera, Pyrodictium, Pyrococcus, and Pyrobaculum. Phyodictium brockii (T.sub.opt 105.degree. C.) is an obligate autotroph which obtains energy be reducing S.sup.0 to H.sub.2 S with H.sub.2, while Pyrobaculum islandicum (T.sub.opt 100.degree. C.) is a faculative heterotroph that uses either organic substrates or H.sub.2 to reduce S.sup.0. In contrast, Pyrococcus furiosus (Topt 100.degree. C) grows by a fermentative-type metabolism rather than by S.sup.0 respiration. It is a strict heterotroph that utilizes both simple and complex carbohydrates where only H.sub.2 and CO.sub.2 are the detectable products. The organism reduces elemental sulfur to H.sub.2 S apparently as a form of detoxification since H.sub.2 inhibits growth.
Patents 183
Web site: http://www.delphion.com/details?pn=US06489150__ •
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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Serum-and steroid-free culture media for cerebellar granule neurons Inventor(s): Belcher; Scott M. (5824 Lee Ave., Little Rock, AR 72205) Assignee(s): None Reported Patent Number: 6,506,576 Date filed: August 9, 2001
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Abstract: The invention is a system for maintenance and high-throughput analysis of cerebellar granule neurons in tissue culture plates under chemically defined conditions. The invention includes serum-free granule culture medium, which is composed of high glucose Dulbecco's Modified Eagle Media (DMEM), NaHCO3, sodium pyruvate, and HEPES, which is subsequently adjusted to pH 7.2. The HEPES buffered DMEM is then supplemented with L-glutamine, KCl, bovine albumin, insulin, transferrin, selenium, penicillin, and streptomycin. Unlike proprietary neuronal culture media, this invention does not include any serum, steroid hormones, phenol red, or added anti-oxidants. The serum-free granule culture medium is then placed in conventional poly-lysine coated tissue culture plates in order to conduct subsequent assays. The invention also includes the ability to package the complete neuronal culture system into a "kit" for isolation, maintenance, treatment, and analysis of cerebellar neurons. A kit would include all the necessary culture medium preparations, tissue culture plates with an appropriate cellular attachment matrix, reagents, disposables and protocols. The kit could be used to evaluate neuronal viability, growth, the role of steroid hormones on neuronal function, drug or toxicant-induced changes in gene expression, or other bioassays. In addition, the invention will be useful in the field of pharmocogenomics because of the ability to analyze small sample sizes. Excerpt(s): The present invention relates to neuronal culture media that may be used for high-throughput analyses. The ability to maintain isolated neurons in primary culture has been critical in advancing our understanding of the functional basis of the nervous system. In primary neuronal culture studies, the use of defined culture conditions is essential for controlling the concentration of components, such as hormones and growth factors, which may affect the growth and development of cultured neurons. Primary cultures of cerebellar neurons are an important in vitro model system that has been used because of their small size, the ease with which large numbers of cells can be isolated, and the resulting physical properties. Neonatal rat or mouse cerebellar granule cells are convenient and frequently used in studies with aims ranging from the identification of factors involved in neurogenesis, development, and migration to defining mechanisms of neurotoxicity and cell death (Cull-Candy, et al., J Physiol, 400: 189-222, 1988; Pemberton, et al. J Physiol, 510: 401-420, 1998; Bhave et al., J Neurosci, 19: 3277-3286, 1999). Because cultured granule cells express both Ca.sup.++ permeable-NMDA and non-NMDA glutamate receptors, these neurons are also an important model used for the analysis of neuronal excitotoxicity (Carroll et al., Neurochem Int, 33: 23-28, 1998; Lim and Ho, J Neurochem, 69: 581-593, 1998). Web site: http://www.delphion.com/details?pn=US06506576__ •
Serum-free cell growth medium Inventor(s): Erlacher; Ludwig (Vienna, AT), Luyten; Frank P. (Kraainem, BE) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,617,161 Date filed: May 9, 2001 Abstract: A chemically defined-serum free growth medium for the in vitro and ex vivo of cells and cell lines. The medium consists of about a one to one ratio (v/v) of two basal growth media containing.alpha.-ketoglutarate, insulin, transferrin, selenium, bovine serum albumin, linoleic acid, ceruloplasmin, cholesterol, phosphatidylethanolamine,.alpha.-tocopherol acid succinate, reduced glutathione, taurine,
Patents 185
triiodothyronine, hydrocortisone, parathyroid hormone, L-ascorbic acid 2-sulfate,.beta.glycerophosphate, PDGF, EGF and FGF. Chondrocytes, when cultured in this medium in the presence of a cartilage derived morphogenetic protein or bone morphogenetic protein, retain their cartilaginous phenotype. Excerpt(s): The present invention relates to a cell growth medium. More specifically, the invention relates to a chemically defined serum-free growth medium useful for the expansion of primary cells or cell lines in culture. Culturing of mammalian cells is an essential technique for research into cellular processes, production of recombinant therapeutic proteins, and generation of expanded cells for transplantation purposes. Cell culture studies have led to the determination of numerous metabolic processes and the identification of growth factors, hormones and their receptors (Bio Techniques, 5:534542, 1987). The composition of media used to culture cells is of paramount importance because of its influence on cell survival and cell response to various effectors. Conventional cell culture media comprise basal nutrient media supplemented with serum from various sources, most often fetal bovine serum, horse serum or human serum. However, the use of serum is undesirable for several reasons. Growth media containing serum may vary in composition, hormone content, and contaminants, thereby introducing extraneous factors and/or infections agents into the culture system (Bio Technology, 11:49-53, 1993; Pharm. Technol., 48:56, 1987). In addition, serum is expensive, impractical for large-scale production of therapeutics. Further, variance between serum lots and laboratory protocols is also a problem. Recent concerns by the FDA, the European community, and others about serum quality, contamination (i.e., bovine spongiform encephalopathy, bovine immunodeficiency virus), and increased demand have generated significant interest in the development and utility of serum-free growth media. Web site: http://www.delphion.com/details?pn=US06617161__ •
Spray-drying microcapsules using an aqueous liquid containing a volatile liquid Inventor(s): Johnson; Richard Alan (West Bridgford, GB), Osborne; Nicholas (Colwick, GB), Sutton; Andrew Derek (Ruddington, GB) Assignee(s): Quadrant Healthcare (uk) Limited (ruddington, Gb) Patent Number: 6,623,722 Date filed: February 13, 1998 Abstract: A process for forming microcapsules comprising (i) providing a solution of a protein in an aqueous solvent and (ii) spraying the said solution into a gas such that the aqueous solvent evaporates, thereby forming hollow microcapsules, characterised in that the aqueous solution contains a liquid of greater volatility than water.The protein is preferably albumin and the volatile liquid is preferably ethanol.The microcapsules may be used as ultrasound echogenic contrast agents. Excerpt(s): The present invention relates to the preparation of hollow proteinaceous microcapsules. One use for these microcapsules is to enhance ultrasound imaging. The fact that air bubbles in the body can be used for echocardiography has been known for some time. U.S. Pat. No. 4,420,442 (Sands; PQ Corpn) discloses adding organic solvents to dispersions of film-forming solids, before the suspensions are spray-dried to form hollow microspheres, but the solvents (for example cellosolve or diglyme) were less volatile than water. Web site: http://www.delphion.com/details?pn=US06623722__
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Supported mesoporous carbon ultrafiltration membrane and process for making the same Inventor(s): Agarwal; Hans (Newark, DE), Foley; Henry C. (State Collage, PA), Strano; Michael (Wilmington, DE) Assignee(s): The University of Delaware (newark, De) Patent Number: 6,719,147 Date filed: April 27, 2001 Abstract: A novel supported mesoporous carbon ultrafiltration membrane and process for producing the same. The membranes comprise a mesoporous carbon layer that exists both within and external to the porous support. A liquid polymer precursor composition comprising both carbonizing and noncarbonizing templating polymers is deposited on the porous metal support. The coated support is then heated in an inertgas atmosphere to pyrolyze the polymeric precursor and form a mesoporous carbon layer on and within the support. The pore-size of the membranes is dependent on the molecular weight of the noncarbonizing templating polymer precursor. The mesoporous carbon layer is stable and can withstand high temperatures and exposure to organic chemicals. Additionally, the porous metal support provides excellent strength properties. The composite structure of the membrane provides novel structural properties and allows for increased operating pressures allowing for greater membrane flow rates.The invention also relates to the use of the novel ultrafiltration membrane to separate macromolecules from solution. An example is shown separating bovine serum albumin from water. The membrane functions by separating and by selective adsorption. Because of the membrane's porous metal support, it is well suited to industrial applications.The unique properties of the supported mesoporous carbon membrane also allow the membrane to be used in transient pressure or temperature swing separations processes. Such processes were not previously possible with existing mesoporous membranes. The present invention, however, possesses the requisite physical properties to perform such novel ultrafiltration processes. Excerpt(s): This invention relates to the field of filtration membranes, generally, and specifically to the field of mesoporous membranes, particularly ultrafiltration and diafiltration membranes. The invention also relates to the novel process of using supported porous carbon membranes for selective adsorption and separation. Membrane filtration technologies are critical to a variety of industrial process applications including cell harvesting, sterilization of biological solutions, clarification of antibiotics, concentration of protein solutions, and particulate filtration. Ultrafiltration is a particular type of membrane separation process that is used to separate macromolecules such as proteins from solutions containing solvents and low molecular weight solutes under the presence of a pressure gradient. Ultrafiltration membranes typically have a pore size from 1 nm to 100 nm. Diafiltration is similar to ultrafiltration, except that changes are made to the solution during processing; in diafiltration the dilution level is typically manipulated during filtration. Membranes used for either of these purposes have the ability to fractionate macromolecular components based upon their individual molecular masses. The typical membrane molecular weight cut-off range is from about 10.sup.3 to 10.sup.7 g/mol. Ultrafiltration is typically carried out with the solution to be processed (rententate) on one side of the membrane and the purified stream (permeate) exiting the system on the other side. The rejected-stream side is operated under higher pressure than the permeate side creating a pressure gradient that drives the solution through the porous membrane structure. The desired
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component or components remain behind, blocked or retained by their inability to permeate the membrane. Web site: http://www.delphion.com/details?pn=US06719147__ •
Test for rapid evaluation of ischemic states and kit Inventor(s): Bar-Or; David (Englewood, CO), Lau; Edward (Boulder, CO), Winkler; James V. (Denver, CO) Assignee(s): Ischemia Techologies, Inc. (arvada, Co) Patent Number: 6,492,179 Date filed: October 2, 1998 Abstract: The present invention relates to a rapid method for the detection of ischemic states and to a kit for use in such a method. Provided for is a rapid method of testing for the existence of and quantifying ischemia based upon method of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating blood, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay sepcific to the alterated form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring human albumin (including no additional chemical group), for detection and quantification of an ischemic event. Excerpt(s): The present invention relates to a rapid method for the detection of ischemic states and to a kit for use in such a method. More particularly, the invention relates to the measurement of a bound specific transition element to human serum to determine the presence or absence of ischemia. Ischemia is the leading cause of illness and disability in the world. Ischemia is a deficiency of oxygen in a part of the body causing metabolic changes, usually temporary, which can be due to a constriction or an obstruction in the blood vessel supplying that part. The two most common forms of ischemia are cardiovascular and cerebrovascular. Cardiovascular ischemia, in which the body's capacity to provide oxygen to the heart is diminished, is the leading cause of illness and death in the United States. Cerebral ischemia is a precursor to cerebrovascular accident (stroke) which is the third leading cause of death in the United States. The continuum of ischemic disease includes five conditions: (1) elevated blood levels of cholesterol and other blood lipids; (2) subsequent narrowing of the arteries; (3) reduced blood flow to a body organ (as a result of arterial narrowing); (4) cellular damage to an organ caused by a lack of oxygen; (5) death of organ tissue caused by sustained oxygen deprivation. Stages three through five are collectively referred to as "ischemic disease," while stages one and two are considered its precursors. Web site: http://www.delphion.com/details?pn=US06492179__
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Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof Inventor(s): Desai; Neil P. (Los Angeles, CA), Magdassi; Shlomo (Jerusalem, IL), SoonShiong; Patrick (Los Angeles, CA), Tao; Chunlin (Beverly Hills, CA), Yang; Andrew (Rosemead, CA), Yao; Zhiwen (Culver City, CA) Assignee(s): American Bioscience, Inc. (santa Monica, Ca) Patent Number: 6,528,067 Date filed: December 7, 1999 Abstract: In accordance with the present invention, there are provided stabilized total nutrient admixture (TNA) compositions which are useful for the in vivo parenteral delivery of pharmacologically acceptable lipids or fats, as well as methods for the preparation thereof. In particular, the pharmacologically acceptable lipid or fat is contained within a protein walled shell. In a particular embodiment of the invention, a TNA composition using human serum albumin (HSA) as a stabilizer has been prepared as a convenient three-in-one formulation (i.e., containing a fat emulsion, dextrose, and amino acids plus electrolytes). This "three-in-one" formulation can be prepared in liquid form or in dry form (comprising submicron-sized nanoparticles). The dried material is stable, even under long term storage, and is easily reconstituted immediately before use by simply adding sterile water (with or without vitamin supplementation) This serves to rehydrate the powder into a TNA suitable for injection. The long shelf life, ease of reconstitution, and single-component injectability of invention compositions provide significant cost savings, as such compositions can be reconstituted and administered safely, even in the home. In addition, HSA, the stabilizing agent of choice for use in the practice of the present invention, has been shown to improve survival and wellness when given as a supplement to patients receiving conventional forms of total nutrient admixtures. Excerpt(s): The present invention relates to stabilized liquid and solid compositions useful as total nutrient admixtures (TNA), as well as methods for the preparation thereof. Invention compositions are easily reconstituted with water to form multicomponent or three-in-one TNA compositions (i.e., containing fat emulsions, dextrose, and amino acids with electrolytes) suitable for parenteral administration of nutrition. Dextrose and amino acids have been the major components of glucose-based parenteral nutrition systems, with an optimal infusion rate of approximately 400 grams of dextrose per day for a 70-kg person. The addition of intravenous fat emulsions has improved patient care by preventing the development of essential fatty acid deficiencies, and by providing a calorically dense product to supplement nonprotein calories. Traditionally, intravenous fat emulsions have been infused separately from the parenteral nutrition solution (see Warshawsky in Nutrition in Clinical Practice 7:187-196 (1992)). Lipid for intravenous infusion was originally introduced as a 10% isotonic emulsion (Intralipid) which allowed total parenteral nutrition (TPN) to be administered via a peripheral vein, thereby reducing the complications associated with central venous administration. The lipid emulsion also provided a safe and effective method for administering essential fatty acids to patients receiving glucose from TPN. Web site: http://www.delphion.com/details?pn=US06528067__
Patents 189
Patent Applications on Albumin 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 albumin: •
Albumin fusion proteins Inventor(s): Ballance, David J.; (Berwyn, PA), Prior, Christopher P.; (Rosemont, PA), Sadeghi, Homayoun; (Doylestown, PA), Sleep, Darrell; (West Bridgford, GB), Turner, Andrew J.; (Eagleville, PA) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030199043 Date filed: April 12, 2001 Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disordrs or conditions using albumin fusion proteins of the invention. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119(e) based on the following U.S. provisional applications: No. 60/229,358 filed on Apr. 12, 2000; No. 60/199,384 filed on Apr. 25, 2000; and No. 60/256,931 filed on Dec. 21, 2000. Each of the provisional applications is hereby incorporated by reference in its entirety. The invention relates generally to Therapeutic proteins (including, but not limited to, a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or fragments or variants of albumin. The invention further relates to Therapeutic proteins (including, but not limited to, a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or fragments or variants of albumin, that exhibit extended shelf-life and/or extended or therapeutic activity in solution. These fusion proteins are herein collectively referred to as "albumin fusion proteins of the invention." The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and/or host cells. The invention is also directed to methods of in vitro stabilizing a Therapeutic protein via fusion or conjugation of the Therapeutic protein to albumin or fragments or variants of albumin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same Inventor(s): Tachibana, Katsuro; (Fukuoka-shi, JP), Tachibana, Shunro; (Fukuoka-shi, JP) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030191446 Date filed: March 26, 2003 Abstract: A booster comprising a plurality of microbubbles of a gas in a liquid, e.g. about 4.times.10.sup.7 cells/ml of microbubbles of a gas having a diameter of 0.1 to 100.mu.m in a 3 to 5% human serum albumin solution, and a pharmaceutical liquid composition comprising the booster as set forth above and a medicament, which are useful for the therapy of various diseases together with exposure of ultrasonic, where the therapeutic effects of the medicament is enhanced by the application of ultrasound in the presence of the booster. Excerpt(s): This invention relates to a booster useful for enhancing the effects of ultrasound in the therapy of various diseases and a pharmaceutical liquid composition containing the booster and a medicament which shows enhanced diffusion and penetration of the medicament into the body by applying ultrasound. More particularly, it relates to a booster useful for therapy of various disease by applying ultrasound which comprises a plurality of microbubbles of a gas in a liquid, a pharmaceutical liquid composition comprising a plurality of microbubbles of a gas and a medicament in a liquid, and the use thereof in the therapy of various diseases while applying ultrasound. It is known that various diseases are remedied by the aid of ultrasonic vibration. For example, it is described in Japanese Patent First Publication (Kokai) No. 115591/1977, etc. that percutaneous absorption of a medicament is enhanced by applying an ultrasonic vibration. Japanese Patent First Publication (Kokai) No. 180275/1990 discloses a drug-injecting device which is effective on the diffusion and penetration of the drug by applying an ultrasonic vibration in the step of injecting a drug into a human body via a catheter or a drug-injecting tube. U.S. Pat. Nos. 4,953,565 and 5,007,438 also disclose the technique of percutaneous absorption of medicaments by the aid of ultrasonic vibration. It is also reported that a tumor can be remedied by concentratedly applying ultrasound from outside the body. In order to enhance the therapeutic effects with ultrasound, it is required to apply a high energy ultrasonic vibration. However, ultrasonic vibration at an energy that is too high causes disadvantageously bums or unnecessary heat at the portion other than the desired portion. On the other hand, when the energy of an ultrasonic vibration is lowered for eliminating such disadvantages, there is a problem of less effect of the ultrasound at the desired portion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition for therapeutic and cosmetic botulinum toxin Inventor(s): Borodic, Gary; (Canton, MA) Correspondence: Milbank, Tweed, Hadley & Mccloy, Llp; One Chase Manhattan Plaza; New York; NY; 10005; US Patent Application Number: 20040037853 Date filed: May 28, 2003
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Abstract: This invention relates to a composition of botulinum based pharmaceuticals used for therapeutic and cosmetic treatment. This invention offers an improvement on the prior art by eliminating the potential of blood-borne contamination with botulinum based pharmaceuticals. Recombinant serum albumin is taught for use in the place of human serum albumin as a stabilizing or enhancing agent. Excerpt(s): I claim priority to U.S. Provisional Patent Application Serial No. 60/383,570, filed May 28, 2002, and hereby incorporate said application by reference herein in its entirety. Human serum albumin ("HSA") is used to stabilize botulinum toxin at high dilutions. This albumin is a human blood product-derived agent from pooled plasma collections. As the molecular weight of the material is low (69,000), filtration generally allows for excellent filtration sterilization, however, prions (non-nucleic acid dependent infectious agents) have become an increasing concern for both federal regulators and the general public. Most physicians and patients do not even know that there are human blood products within BOTOX-.TM., the market leading botulinum toxin product. Prion dependent diseases include Creutzfeld-Jacob disease, Kuru, fatal familial insomnia, and Gertmann-Straussler-Scheinker disease. Although the incidences of these diseases are rare (one in 1,000,000), it has been estimated that one in 10,000 are infected with prions at the time of death. Prion diseases generally cause spongiforma encephalopathies of the brain with serious attendant neurologic symptoms prior to death. Humans are thought to acquire prions in two ways: (1) infection from medical procedures such as surgery, biologic agents, and tissue transplants, and (2) genetically. The impact that these observations have made is to try to limit human blood products in biologic agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositon for culturing cells, in particular animal or tissue cells, and a culture medium comprisiing such a composition Inventor(s): Heron, Antoine; (Halluin, FR) Correspondence: Baker Botts, Llp; 910 Louisiana; Houston; TX; 77002-4995; US Patent Application Number: 20040087021 Date filed: October 15, 2003 Abstract: The invention concerns a composition for the culture of cells, in particular animal cells or tissues, free from animal proteins other than recombinant proteins, of the type including an albumin substitute, a transferrin substitute and an insulin substitute, the said composition being characterized in that the albumin substitute is polyethylene glycol in quantities greater than or equal to 1% by weight. The invention also includes reduced albumin compositions in which part of the albumin is replaced by polyethylene glycol.The invention also includes a culture medium including such a composition and methods of culturing cells or tissues in such compositions or media. Excerpt(s): This application claims foreign priority of the French application FR 0212878 filed on Oct. 16, 2002. The invention concerns a composition for culturing cells, in particular animal or tissue cells, and a culture medium comprising such a composition. In particular, the invention concerns a composition and a cell culture medium containing no animal proteins other than recombinant ones. In the field of in vitro culture media for cells which can be directly used in humans, media are already known whose main constituent is serum. These media do however have drawbacks. First of all, the composition of such media is only partially known, which poses problems in
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particular in terms of functional reproducibility between different serums and between different batches of the same serum. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Coumarin analog compounds for safer anticoagulant treatment Inventor(s): Carter, Daniel C.; (Huntsville, AL) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20040058985 Date filed: July 30, 2003 Abstract: The present invention relates to the albumin-guided development of coumarin analogs and the analogs developed thereby. The coumarin analogs of the present invention are identified and isolated by the fact that they have binding sites to albumin which are different than the binding sites of conventional coumarin analogs such as sodium warfarin, and as a result will be less prone to be displaced since the binding site of sodium warfarin is shared by numerous drugs such as aspirin. The coumarin analogs of the invention are advantageous because they can achieve the effects of the prior coumarin analogs with a minimum of metabolic complications and undesirable side effects. Excerpt(s): This application claims the benefit of U.S. Provisional Application Ser. No. 60/399,126, filed Jul. 30, 2002. The invention relates to the albumin-guided development of certain coumarin analog compounds which can be used as safer and more effective alternatives to previous analogs such as Sodium Warfarin, as well as methods for obtaining the coumarin analogs by assessing and utilizing the albumin-binding characteristics of the individual compounds so that the coumarin analogs of the invention may be identified or designed which will bind at sites which are less likely to be displaced by other drugs and which will thus result in safer, more controlled levels of coumarin analog in the bloodstream. Accordingly, the invention also relates to methods of providing anti-coagulant or anti-thrombotic treatment utilizing effective amounts of the coumarin analogs of the present invention which will have reduced potential for unfavorable drug interactions, reduced metabolic complications, and improved controllability within their therapeutic range. It has long been known to utilize coumarin analogs for various purposes such as to provide anti-thrombotic effects where needed. For example, one such analog known as Sodium Warfarin, which has been marketed under the tradename "Coumadin.RTM." by the DuPont company, is considered the generally accepted standard in the field of coumarin analogs, although this drug has been marketed as a generic drug under other brand names such as Marevan; Prothromadin; Tintorane; Warfarin sodium; Warfilone; and Waran. Coumarin analogs such as sodium warfarin are disclosed, for example, in U.S. Pat. Nos. 2,427,578; 2,765,321; 5,591,403; and 6,512,005, incorporated herein by reference, and these compounds have been utilized primarily for the ability to provide localized antithrombotic effects as needed during therapeutic treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Erythropoietin liposomal dispersion Inventor(s): Delmenico, Sandro; (Schaffhausen, CH), Floether, Frank-Ulrich; (Schaffhausen, CH), Naeff, Rainer; (Langwiesen, CH), Wetter, Andre; (Schaffhusen, CH) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040052838 Date filed: September 10, 2003 Abstract: The present invention relates to a liposome based formulation of erythropoietin comprising:(a) an effective amount of an erythropoietin;(b) a lipidic phase comprising:(i) lecithin or hydrogenated lecithin;(ii) optionally, a charged electropositive or electronegative lipid compound; and(iii) cholesterol or a derivative thereof selected from cholesterol esters, polyethylene glycol derivatives of cholesterol (PEG-cholesterols), and organic acid derivatives of cholesterols; and(c) a phosphate buffer.The liposome based parenteral dosage form of the invention is prepared by means of an ethanol injection technique. The composition avoids the need for use of human serum albumin and exhibits superior stability. Excerpt(s): The present invention relates to a liposome based formulation of erythropoietin. In particular, the invention relates to a liposome based parenteral dosage form of erythropoietin prepared by means of an ethanol injection technique which exhibits superior stability. Erythropoietin (EPO) is a glycoprotein which serves as the principal factor involved in the regulation of red blood cell synthesis. Erythropoietin is produced in the kidney and acts by stimulating precursor cells in the bone marrow causing them to divide and differentiate into mature red blood cells. The recombinantly produced 165 amino acid glycoprotein has been available for some time as an effective therapeutic agent in the treatment of various forms of anemia, including anemias associated with chronic renal failure, zidovidine treated HIV infected patients, and cancer patients on chemotherapy. The glycoprotein is administered parenterally, either as an intravenous (IV) or subcutaneous (SC) injection. Presently, the parenteral formulations in use are conventional sterile buffered aqueous solutions for IV or SC injection which contain human serum albumin (HSA) as a carrier. Such formulations are marketed in the United States under the trade names EPOGEN.RTM. and PROCRIT.RTM. These products contain erythropoietin in 1 ml single dose, preservativefree or 2 ml multidose preserved vials. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Evaluation and preservation solution Inventor(s): Steen, Stig; (Lund, SE) Correspondence: Smith, Gambrell & Russell, Llp; 1850 M Street, N.W., Suite 800; Washington; DC; 20036; US Patent Application Number: 20040029096 Date filed: September 3, 2003 Abstract: An evaluation and preservation solution for human and animal organs, tissues and parts thereof is described, wherein it comprises serum albumin at a concentration of 55-105 g/L, a scavenger and coating compound, preferably dextran compounds and derivatives thereof having essentially the same structure at a concentration of 1-55 g/L
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weight, and a physiological serum concentration of salts and nutrients in a physiologically acceptable medium. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/279 725 filed Mar. 30, 2001 and Swedish Application No. 0004032-9 filed Nov. 3, 2000, all of which are incorporated herein by reference. The present invention relates to an evaluation and preservation solution for human and animal organs and tissues and parts thereof for transplantation, to a method for evaluation of such organs and tissues and parts thereof before transplantation, and to a method for transplantation from a non-heart-beating donor. In clinical organ transplantation today kidneys, livers, hearts and lungs are the common transplanted organs. Pancreas is still not very often transplanted, and transplantation of small bowels and other organs are at the experimental stage. Regarding the preservation of kidneys, livers, hearts and lungs, the golden standard is cold ischemic preservation. This means that the organ which is to be preserved is flushed with a cold preservation solution and after that the organ is immersed in the same cold solution until it can be transplanted. The most common organ preservation solution used today is the University of Wisconsin solution (UW). For the preservation of kidneys and livers UW is the most frequently used preservation solution. Even for hearts it is used more and more, but for hearts St Thomas solution in different modifications is still the most common solution. A new solution used in heart preservation in the last few years is Celsior, which is a solution very similar to UK, except that the potassium concentration is much lower. For lungs Euro-Collins solution is still the most frequently used solution, but Perfadex is used increasingly. What all these solutions have in common is that initially stated, i.e. that the organs are flushed with a cold solution and after that immersed in the same cold solution. For kidneys and livers good preservation for up to 24 hours is obtained clinically, for lungs most transplant surgeons accept 6 hours and for hearts 4 hours of cold ischemic time. The organs to be transplanted have hitherto been obtained from so called brain-dead but heart-beating donors or from non-heart-beating persons within minutes after death, where the possibilities for acute harvesting and permission from next of kin to do it happened to be present; such cases are rare, and will not solve the donor organ shortage. This is also accepted for livers and kidneys. However, if organ donation from non-heart-beating donors will be a controlled clinical procedure, there is a need for an evaluation/preservation solution for organs from non-heart-beating donors, but so far no satisfactory solutions for this purpose have been produced. If this problem of lack of a convenient solution of this type could be solved, a larger number of organs would be available for transplantation, and the problem of lacking organs could be substantially eliminated. At the moment, thousands of people world-wide are dying or suffering while waiting for organs for transplantation. None of the solutions in use at present for cold ischemic preservation could be used as evaluation solutions for organs from a nonheart-beating donor. University of Wisconsin solution and Euro-Collins solution have an intracellular potassium content, which gives vascular spasm at normothermia, and the same will St Thomas and Celsior do, although not to the same degree. Perfadex, which is a low potassium-dextran solution and could be used if mixed with erythrocytes, has not the oncotic pressure necessary for perfusing, e.g. lungs without oedema development. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Fat replacement material and method of manufacture thereof Inventor(s): Campbell, Lydia Johanna; (Milnathort, GB) Correspondence: Venable Baetier Howard & Civiletti; P O Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20040047974 Date filed: June 19, 2003 Abstract: The present invention provides a method for the manufacture of a fat replacement material suitable for use in the manufacture of food products. The method comprises the steps of: a) providing a substantially homogeneous aqueous fluid containing albumin and at least one stabilizer selected from a sugar and salt; b) subjecting the fluid to a controlled heat treatment at a temperature and for a period of time not less and not greater than that sufficient for obtaining from 50 to 100% denaturation of the albumin; and c) spray drying of the heat treated fluid. The invention also provides a fat replacement material comprising a spray dried powder comprising an intimate admixture of 1 part by weight of from 50 to 100% denatured albumin, and from 3 to 100 parts by weight of at least one stabilizer selected from a sugar and salt. The material of the invention has excellent emulsifying properties as well as improved heat stability and resistance to acid conditions. Excerpt(s): The present invention relates to the manufacture of a fat replacement material suitable for use in the food industry. It has previously been proposed to use albumin proteins such as whey and egg white to substitute for fat to a greater or lesser extent so as to produce low-fat food products for which there is an ever increasing demand. It is however particularly important for safety reasons, when using albumin to ensure that it is properly pasteurized. When albumin is subjected to heat treatment, though, there is a considerable risk of the albumin coagulating and/or being hydrolyzed, which generally results in processing difficulties and adverse effects on the texture, mouth-feel, and other properties of the final food product in which it is used. Conventionally therefore manufacturers have gone to considerable lengths to avoid any denaturation of the albumin as far as possible in order to prevent the albumin from coagulating. Whey is generally defined as the liquid byproduct from the manufacture of cheese and casein by the acid or rennet coagulation of milk. The whey obtained from acid coagulation is called acid whey and that obtained from rennet coagulation, sweet whey. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Foam-forming wound dressing Inventor(s): Sierra, David; (Aptos, CA) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20030211137 Date filed: March 27, 2003 Abstract: This invention relates generally to a foamed-wound dressing containing albumin and at least one other protein. The foam dressing is prepared initially as a liquid composition, but forms a foam when a shear force is applied to the liquid. The wound dressing can be prepared as a foam in situ on the surface of the wound or can be
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pre-formed as a foam and then later applied to a wound. A biocompatible foam wound dressing for human can be prepared using human proteins. Excerpt(s): This invention relates to foam-forming wound dressing materials and methods to prepare and use such materials. Large scale burn wounds and other open wounds with skin loss often require treatment with temporary skin dressing. The purpose of temporary dressings is to provide immediate coverage and protect the wound from further injury; reduce the rate of evaporative water loss and associated heat loss; prevent or minimize infection; absorb materials exuded from the wound, including dead leukocytes, epidermal and dermal cells; and encourage vascularization and tissue regeneration in the wound. These factors are particularly relevant to traumatic wounds and burns such as those that occur in the field away from emergency medical treatment. Traditionally, wounds have been encouraged to heal by placing a gauze material over the wound. More recently, a number of products have been introduced in the market that have been used as temporary wound dressings. These include, for example, gels, synthetic foams, and acrylic polymer spray solutions. However such dressings are expensive to produce and/or fail to provide sufficient advantages over traditional dressings. Thus, a need exists for temporary a wound dressing that is low cost, easy to use, and provides superior properties over conventional dressings. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Fusion polypeptides of human serum albumin and a therapeutically active polypeptide Inventor(s): Fleer, Reinhard; (Bures-sur-Yvette, FR), Fournier, Alain; (ChatenayMalabry, FR), Guitton, Jean-Dominique; (Paris, FR), Jung, Gerard; (Montlhery, FR), Yeh, Patrice; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040086976 Date filed: November 7, 2003 Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides. Excerpt(s): The present invention relates to new biologically active polypeptides, their preparation and pharmaceutical compositions containing them. More particularly, the present invention relates to essentially recombinant polypeptides composed of an active part derived from a natural or artificial polypeptide having a therapeutic activity and coupled to an albumin or to a variant of albumin. It is understood that the therapeutic activity of the polypeptides of the invention can be either direct (treatment of diseases), or indirect (and for example capable of being used in the prevention of diseases, in the design of vaccines, in medical imaging techniques and the like). It is understood in the following text that the albumin variants designate any protein with a high plasma halflife which is obtained by modification (mutation, deletion and/or addition), by genetic engineering techniques, of a gene encoding a given isomorph of human serum albumin, as well as any macromolecule with a high plasma half-life obtained by in vitro
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modification of the protein encoded by such genes. Albumin being highly polymorphic, numerous natural variants have been identified and classified [Weitkamp L. R. et al., Ann. Hum. Genet. 37 (1973) 219]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Genetic analysis of peyer's patches and M cells and methods and compositions targeting peyer's patches and M cell receptors Inventor(s): Brayden, David; (Glenageary, IE), Byrne, Daragh; (Baumont, IE), Higgins, Lia; (Donabate, IE), Lambkin, Imelda; (Sutton, IE), O'Mahony, Daniel; (Blackrock, IE) Correspondence: Caesar, Rivise, Bernstein, Cohen & Pokotilow, LTD.; Attn: Elan; 12th Floor, Seven Penn Center; 1635 Market Street; Philadelphia; PA; 19103-2212; US Patent Application Number: 20030211476 Date filed: April 4, 2002 Abstract: Methods of increasing of or decreasing the levels of a protein in a PP cell; methods of increasing antigen, vaccine, DNA vaccine delivery to M cells, use of human serum albumin and other transport enhancing proteins to enhance oral drug delivery; use of calreticulin to enhance oral antigen delivery, use of other cell surface proteins, receptors, and transporters to enhance delivery to M cells of antigens or vaccine delivery vehicles, use of other cytoplasmic proteins to regulate intracellular trafficking and delivery to mucosal immune sampling and processing systems. Excerpt(s): This application claims the benefit of U.S. provisional application No. 60/281,387 filed Apr. 4, 2001, and U.S. provisional application No. 60/302,591 filed Jul. 2, 2001. This invention relates to the genetic analysis of M cells and methods and compositions targeting M cell receptors. The Peyer's patch of the intestinal lining is a specialized tissue that allows the immune system to identify foreign antigens that require an immune response. It is also a potential pathway for orally delivered drugs to cross the intestinal barrier into the bloodstream. Central to these properties are M cells, which populate the patch's epithelial sheet. In view of the importance of the Peyer's patch and its M cells for the immune response and drug delivery, it is desirable to identify the cell proteins important for these phenomena. It is also desirable to increase the amounts of such important proteins in order to either facilitate the immune response and drug delivery or promote the conversion of non-M cells to M cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hepatotropic conjugates of antiblastic drugs accomplishing a loco-regional chemotherapy of liver micrometastases after adminstration by peripheral venous route Inventor(s): Busi, Corrado; (Bologna, IT), Di Stefano, Giuseppina; (Bologna, IT), Fiume, Luigi; (Bologna, IT) Correspondence: James R Haller; Fredrikson & Byron; 4000 Pillsbury Center; 200 South Sixth Street; Minneapolis; MN; 55402-1425; US Patent Application Number: 20040044178 Date filed: July 9, 2003
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Abstract: Pharmaceutical compositions containing as active compound conjugates of lactosaminated albumin with antiblastic nucleosides (and their analogs) are here described. These compositions are particularly useful to increase the efficacy of the antiblastic nucleosides (and their analogs) on liver micrometastases. They preferably consist of aqueous solutions administered by parenteral route, preferably by intravenous injection. The antiblastic nucleoside of choice is 5-fluoro-2'-deoxyuridine (FUdR). Excerpt(s): The present invention refers to pharmaceutical compositions containing as active compound conjugates of antiblastic nucleosides (and their analogs), preferably FUdR, with lactosaminated albumin (L-SA) and, more particularly, with lactosaminated human albumin (L-HSA). These conjugates are particularly useful to increase the efficacy of the antiblastic nucleosides (and their analogs) on liver micrometastases (avascular metastases nourished by the blood of liver sinusoids). The conjugates selectively enter into hepatocytes and release the drugs into liver blood in pharmacologically active amounts. Colorectal cancer is one of the most common malignant disease with about half million deaths and more than 700,000 new cases diagnosed worldwide each year (Pisani P., et al. "Estimates of the world wide mortality. " Int J Cancer 1993, 55, 891-903). Hepatic metastases develop in 60% of patients with colorectal cancer and autopsy studies have shown that metastatic disease remains confined to the liver in a third of patients who die of this tumor (Kemeny N., et al. "Hepatic arterial infusion. " New Engl J Med 1999, 341, 2039-2048). Fluoropyrimidines (5-fluoro-2'-deoxyuridine (FUdR) and its precursor 5-fluorouracil (FU)) are the drugs of choice for the post-operative chemotherapy of metastases from colon carcinoma (Robustelli Della Cuna G., Gennari L. "Neoplasie dell'apparato digerente" in Bonadonna G., Robustelli Della Cuna G. "Medicina Oncologica", Masson, Milano, Parigi, 1999). Fluoropyrimidines are characterised by high hepatic extraction: in patients receiving these drugs by peripheral venous administration, the levels of FUdR (Ensminger W. D., et al. "A clinical-pharmacological evaluation. " Cancer Res 1978, 38, 3784-3792) and of FU (Wagner J. G., et al. "Steady-state non linear pharmacokinetics. " Cancer Res 1986, 46, 1499-1506) are lower in hepatic veins than in systemic circulation. This extraction causes cells of liver micrometastases (early metastases nourished by the blood of liver sinusoids) to be exposed to drug concentrations lower than those achievable in systemic circulation. This is a serious disadvantage, since micrometastases should be one of the major targets of post-operative chemotherapy. To increase the efficacy of fluoropyrimidines on liver micrometastases these drugs were locally administered through portal vein (Taylor I., et al. "Randomised controlled trial. " Br J Surg 1985, 72, 359-363; Fielding L. P., et al. "Randomised controlled trial. " Lancet 1992, 340, 502-506; Liver Infusion Meta-analysis Group "Portal vein chemotherapy. " J Nat[ Cancer Inst 1997, 89, 497-505; Rougier P., et al. "Adjuvant portal vein infusion. " Lancet 1998, 351, 1677-1681). However, portal vein infusion requires laparatomy and the inserted catheter often causes complications. In recent years, it was observed that nucleoside analogs (NAs) (the chemical family of FUdR) when coupled to peptides exposing galactosyl residues (e.g. lactosaminated poly-L-lysine (L-poly(LYS)) selectively enter into hepatocytes after binding to the asialoglycoprotein receptor expressed only on hepatocyte surface (Fiume L., et al. "Liver targeting. " J Viral Hep 1997, 4, 363-370). It was found that, after the intracellular release from the carrier, NAs partly exit from hepatocytes into bloodstream (Fiume L., et al. "Coupling to lactosaminated poly-Llysine. " J Hepatol 1998, 29, 1032-1033; Di Stefano G., et al. "Inhibition of [.sup.3H]thymidine incorporation. " Biochem Pharmacol 1999, 57, 793-799). Although this exit reduces the efficacy of hepatocyte targeting, it may have a useful consequence, since H results in higher NA concentrations in hepatic blood than in systemic circulation
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(Di Stefano G., et al. "Enhanced liver blood concentrations. " Biochem Pharmacol 2000, 59, 301-304). Therefore, administration of antiblastic nucleosides (and their analogs) coupled to galactosylated peptides, such as L-poly(LYS), could reproduce the locoregional chemotherapy performed by the intra-portal infusion of fluoropyrimidines with the advantage of avoiding the drawbacks of this invasive procedure and permitting repeated cycles of treatment. The feasibility of this approach received support by the finding that in mice a conjugate of FUdR with L-poly(LYS) released the drug in liver blood in amounts high enough to inhibit the growth of hepatic metastases (Di Stefano G., et al., "Coupling of fluorodeoxyuridine to lactosaminated. " Biochem Pharmacol 2001, 61, 457-463). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunoassay method/equipment, biological component measurable toilet, antialbumin monoclonal antibody, cell strain producing the same, and albumin detection kit Inventor(s): Kamei, Akihito; (Kyoto, JP), Kawamura, Tatsurou; (Kyoto, JP), Shigetoh, Nobuyuki; (Kyoto, JP), Yugawa, Keiko; (Nara, JP) Correspondence: Jack Q. LEVER,JR.; Mcdermott, Will & Emery; 600 Thirteenth Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20030219910 Date filed: May 20, 2003 Abstract: The immunoassay method of this invention measures the content of a subject substance in a sample. The method includes the steps of: (a) preparing a mixed solution by mixing the sample and an antibody solution including a first monoclonal antibody and a second monoclonal antibody capable of specifically binding to the subject substance; and (b) measuring an optical property of the mixed solution. The first monoclonal antibody is capable of binding to a first epitope of the subject substance, and the second monoclonal antibody is capable of binding to a second epitope of the subject substance different from the first epitope. Each of the first and second epitopes exists singly in the subject substance. Excerpt(s): The present invention relates to an immunoassay method for measuring a specific component in a sample. Conventionally, various immunoassay methods using antibodies have been proposed as methods for measuring a specific component (subject substance) in a sample easily without involving dilution or agitation of a sample liquid. Immunoturbidimetry is known as one of the immunoassay methods. An assay kit used for immunoturbidimetry (Microalbumin-HA TestWako of Wako Pure Chemicals Industries, Ltd) is commercially available. This assay kit is essentially composed of a buffer (50 mM Good's buffer, pH 7.4) and an antibody solution. The antibody solution includes a rabbit-derived anti-human albumin polyclonal antibody (1.5 mg Ab/ml) and a mouse-derived anti-human albumin monoclonal antibody (4.0 mg Ab/ml). In measurement, a sample is allowed to act with the antibody solution in the buffer. If albumin is included in the sample, the albumin specifically reacts with the anti-human albumin antibodies as an antigen-antibody reaction, turning the solution turbid. The degree of being turbid (turbidity) is proportional to the concentration of albumin in the sample. By measuring the turbidity, therefore, the albumin amount in the sample can be determined. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Kit for assaying saccharified protein Inventor(s): Sode, Koji; (Tokyo, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030226769 Date filed: February 4, 2003 Abstract: A novel method of assaying glycated hemoglobin, glycated albumin or a fructosamine which is a degradation product thereof are disclosed. In particular, the present invention provides a method for assaying fructosamine which comprises oxidizing fructosamine by using a compound having an imidazole group as a catalyst in the presence of an appropriate mediator (an electron acceptor), and measuring the reduced form of the mediator. Excerpt(s): The present invention relates to a novel method for assaying glycated proteins. More specifically, it relates to a method for assaying glycated hemoglobin (HbA1c), glycated albumin, and fructosyl-valine or fructosamine which is a degradation product of these proteins, as well as an assay reagent and a sensor for use in the method. The method of the invention my be used in the field of, for example, clinical laboratory tests. Fructosamine oxidases that act upon amadori compounds have been isolated from various species. It has been suggested that glycated albumin, HbA1c, and other glycated proteins and fructosamines can be assayed by the use of fructosamine oxidase (Japanese Patent Public Disclosure No. 61-268178, No. 61-280297, No. 03-155780, No. 05192193, No. 07-289253, and No. 08-154672; Agric. Biol. Chem., 53(1), 103-110,1989; Agric. Biol. Chem., 55(2), 333-338,1991; J. Biol. Chem., 269(44), 27297-27302, 1994; Appl. Environ. Microbiol., 61(12), 4487-4489, 1995; Biosci. Biotech. Biochem., 59(3), 487-491, 1995; J. Biol. Chem., 270(1), 218-224, 1995; J. Biol. Chem., 271(51), 32803-32809,1996; J. Biol. Chem., 272(6), 3437-3443,1997). It would be desirable to improve the stability of fructosamine oxidases and provide a novel catalyst capable of catalyzing oxidation of fructosamines. It is also desirable to provide a method for assaying glycated hemoglobin (HbA1c), glycated albumin and other glycated proteins by measuring fructosamines, as well as assay reagents and sensors for use in clinical laboratory tests. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Latent reactive blood compatible agents Inventor(s): Amos, Richard A.; (St. Anthony, MN), Anderson, Aron B.; (Minnetonka, MN), Everson, Terrence P.; (Eagan, MN), Guire, Patrick E.; (Eden Prairie, MN) Correspondence: Philip M. Goldman; Fredrikson & Byron, P.A.; 4000 Pillsbury Center; 200 South Sixth Street; Minneapolis; MN; 55402-1425; US Patent Application Number: 20030215419 Date filed: April 24, 2003 Abstract: A reagent and related method for use in passivating a biomaterial surface, the reagent including a latent reactive group and a bifunctional aliphatic acid (e.g., fatty acid), in combination with a spacer group linking the latent reactive group to the aliphatic acid in a manner that preserves the desired function of each group. Once bound to the surface, via the latent reactive group, the reagent presents the aliphatic
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acid to the physiological environment, in vivo, in a manner (e.g., concentration and orientation) sufficient to hold and orient albumin. Excerpt(s): The present application is a divisional of U.S. patent application filed Jul. 29, 2002 and assigned Ser. No. 10/207,944, which is a divisional of U.S. patent application filed Oct. 22, 1998 and assigned Ser. No. 09/177,318, which is a continuation of provisional U.S. patent application filed Mar. 18, 1998 and assigned Ser. No. 60/078,383, the entire disclosure of which is incorporated herein by reference. The present invention relates to reagents and methods for rendering a surface biocompatible, and in particular to reagents and methods for "passivating" the surface of an implantable medical device in order to render it hemocompatible. In another aspect, the invention relates to biomedical devices, per se, and in particular those having biocompatible, including hemocompatible, tissue-contacting surfaces. Manufacturers of implantable medical devices have long attempted to understand, and in turn improve, the performance of materials used in blood-contacting applications (Leonard, E. F., et al. Ann. N.Y. Acad. Sci. 516, New York, Acad. Sci., New York, 1987). The biological response of the body, as well as problems with infection, have hindered the application of implantable, disposable, and extracorporeal devices. Anticoagulant drugs, such as heparin and coumadin, can improve the use of such devices, although anticoagulants have their own corresponding risks and drawbacks. For these reasons, development of materials having greater compatibility with blood has been pursued aggressively (Sevastianov, V. I., CRC Crit. Rev. Biocomp. 4:109, 1988). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Macroaggregated albumin-polyethyleneimine (MAA-PEI) lung-targeted delivery of respiratory syncytial virus DNA vaccines Inventor(s): Harcourt, Jennifer L.; (Lilburn, GA), Tripp, Ralph A.; (Decatur, GA) Correspondence: Needle & Rosenberg, P.C.; Suite 1000; 999 Peachtree Street; Atlanta; GA; 30309-3915; US Patent Application Number: 20040009903 Date filed: June 2, 2003 Abstract: The present invention provides a composition comprising: 1) macroaggregated albumin, 2) a nucleic acid comprising a nucleotide sequence encoding an RSV protein, and 3) polyethylamine (PEI), wherein the MAA, PEI and nucleic acid form a complex. Also provided by the present invention is a method of preventing respiratory syncytial virus (RSV) infection in a subject comprising administering to the subject an amount of a composition of this invention. Excerpt(s): This application claims the benefit of priority of U.S. Provisional Application No. 60/384,586, filed May 31, 2002. The 60/384,586 provisional patent application is herein incorporated by this reference in its entirety. This invention relates to compositions and methods for preventing respiratory syncytial virus (RSV) infection. Currently, no safe and effective RSV vaccine is available. DNA vaccines encoding RSV F or G glycoproteins are one RSV vaccine option being examined for safety and efficacy. However, DNA vaccination has been problematic because of the need for repeated vaccination requiring large amounts of DNA, and DNA vaccination does not often result in mucosal immunity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and apparatus for enhancing the integrity of an implantable sensor device Inventor(s): Gottlieb, Rebecca; (Culver City, CA), Miller, Michael E.; (Culver City, CA), Reghabi, Bahar; (Marina del Rey, CA), Shah, Rajiv; (Rancho Palos Verdes, CA), Zhang, Yanan; (Valencia, CA) Correspondence: Foley & Lardner; 2029 Century Park East; Suite 3500; Los Angeles; CA; 90067 Patent Application Number: 20040064156 Date filed: December 31, 2002 Abstract: A method and apparatus for enhancing the integrity of an implantable sensor. Voids formed between an outer tubing and a sensor substrate or spacing element may be back-filled with a curable, implantable material, minimizing the extent to which unwanted fluids diffuse within the sensor. An enzyme or protein matrix pellet below the sensor window may be pre-treated with a reducing agent to enhance its bond stability, and to reduce undesired swelling that may cause the sensor window to detach or leak. The bonding between the enzyme pellet and a hydrogel layer may be reinforced by application of an intervening bonding layer of a protein material, such as human serum albumin (HSA). The size of the window may be minimized by minimizing the size of an underlying electrode, providing reduced flux and lengthening sensor. A coating may be deposited on the surface of the sensor leads, providing stiffening and lubrication. Excerpt(s): Embodiments of the present invention relate to U.S. Provisional Application Serial No. 60/414,142, filed Sep. 27, 2002, entitled "Method and Apparatus for Enhancing the Integrity of an Implantable Sensor Device," which is incorporated by reference herein and is a basis for a claim of priority. The present invention relates generally to the field of medical devices, and, more specifically, to sensor structures for medical implants. The combination of biosensors and microelectronics has resulted in the availability of portable diagnostic medical equipment that has improved the quality of life for countless people. Many people suffering from disease or disability who, in the past, were forced to make routine visits to a hospital or doctor's office for diagnostic testing currently perform diagnostic testing on themselves in the comfort of their own homes using equipment with accuracy to rival laboratory equipment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for kidney disease detection Inventor(s): Comper, Wayne D.; (Victoria, AU) Correspondence: Mcdermott, Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20040029175 Date filed: March 19, 2003 Abstract: A method for diagnosing early stage renal disease and/or renal complications of a disease in which intact albumin is an indicator of the renal disease and/or complications. The method includes an isolated intact protein, an anti-intact protein antibody thereto, and methods for preparing the same. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/892,797 filed on Jun. 28, 2001, which is a continuation-in-part of U.S. patent
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application Ser. No. 09/415,217, filed on Oct. 12, 1999, which claims priority to Australian Patent Application Serial No. PP7843, filed on Dec. 21, 1998, the entire disclosures of which are incorporated herein by reference. The invention relates to improved methods of detecting and treating an early stage of renal disease and/or renal complications of a disease, particularly diabetes. The appearance of excess protein such as albumin in the urine is indicative of kidney disease. Diabetic nephropathy is such a disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for preparing an albumin isolate from a substance containing albumin Inventor(s): Neumuller, Waldemar; (Gottingen, DE) Correspondence: Thomas, Kayden, Horstemeyer & Risley, Llp; 100 Galleria Parkway, NW; Ste 1750; Atlanta; GA; 30339-5948; US Patent Application Number: 20030229206 Date filed: February 13, 2003 Abstract: For preparing an albumin isolate from a substance containing albumin, the substance is first ground to a flour. The flour is then suspended in an aqueous solution. The albumin is extracted from the flour into the solution by an at least two stage extraction process using at least one protease, at a pH greater than 8 and at a temperature between 30 and 60.degree. C. In the first stage the flour is treated at a lower protease to albumin weight ratio, at a lower pH and at a higher temperature than in the second stage. After the first stage, a first upper flow and a fraction containing the flour are separated, and the albumin is precipitated from said upper flow. The fraction containing the flour is subjected to the second extraction stage. After that, a second upper flow is separated and fed back to the first stage. Excerpt(s): This application is a continuation-in-part of copending U.S. application Ser. No. 09/914,343, entitled, "Method For Preparing An Albumin Isolate From A Substance Containing Albumin," of the same title, which is the National Phase of Patent Cooperation Treaty Patent Application having Ser. No. WO 00/49887 filed Feb. 23, 2000, which claims priority to German Patent Application No. DE 199 07 725.8, filed Feb. 23, 1999, all of which are entirely incorporated herein by reference. The invention relates to albumin isolates, and more particularly, to methods for preparing an albumin isolate from a substance containing albumin. Several methods are known to extract albumin from vegetable raw materials, an alkaline extraction of the albumin at a pH of between 7 and 9 and at a temperature of 40 to 50.degree. C. being the basis of these methods. The extracted albumin is then purified by centrifugation and acidified with a mineral acid until the isoelectric point of the albumin is reached. The albumin precipitated at the isoelectric point is again concentrated and purified by means of centrifugation. In this way, yields of 70% as related to the albumin contained in the raw materials are possible. However, it is a serious drawback that only such raw materials may be used in which the albumin has a low level of denaturation. Especially in exploring the most important vegetable albumin isolate, i.e., soya albumin isolate, the limitation to so called "white flakes" as a raw material is an economic drawback. White flakes are only obtained by means of a special drying method for the remainders of soya oil production. Normally, the remainders are dried less carefully, and they are then present in a form of so called "toasted flakes" in which the albumin is strongly denatured. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for reconstituting lyophilized proteins Inventor(s): Grandgeorge, Michel; (Vaugneray, FR), Rapp, Mirna; (Marburg, DE) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040005310 Date filed: March 11, 2003 Abstract: A method for reconstituting lyophilized proteins, in which the reconstitution takes place in a receptacle in which the gas pressure is between 1 mbar and atmospheric pressure, is described. In the lyophilized protein-containing receptacle, the gas pressure of between 1 mbar and atmospheric pressure, which gas pressure is required in accordance with the invention, is set by introducing air or an inert gas, and the quantity of water for injection purposes which is required for dissolving the protein is added. The method is particularly suitable for blood coagulation factors, the von Willebrand factor and albumin. Excerpt(s): The invention relates to a method for reconstituting lyophilized proteins in which optimal dissolution behavior of the protein is ensured by setting defined pressure ratios during reconstitution. It is customary to use a freeze drying, which is termed lyophilization, to convert proteins which are used as pharmaceuticals into a form which can be stored over a relatively long period of time and, in connection with this, preserve their biological activity. In freeze drying, the labile proteins are frozen rapidly and carefully under sterile conditions, after which the water, which has been converted into ice, is rapidly removed by sublimation under high vacuum conditions. At the same time, the substance which is to be dried remains in the frozen state due to the cold arising from the evaporation. When lyophilizates are prepared in practice, the solutions containing the protein are customarily aliquoted into small receptacles which are designed for the vapor release, after which what are termed lyophilization stoppers are put on them and they are introduced into a freeze drying chamber. While still on the shelves, the receptacles are then sealed in the freeze drying chamber by the shelves being pressed together hydraulically or manually, with the stoppers being pressed down into the receptacles. This ensures that the vacuum in the receptacles is comparable with that in the freeze drying chamber. Subsequently, the chamber is ventilated, and the receptacles, containing the finished lyophilizates, are removed and subsequently sealed with flange caps and packed ready for use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of detecting saccharified albumin Inventor(s): Taguchi, Michihiro; (Saitama, JP), Tsuboi, Isami; (Saitama, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20040048387 Date filed: June 9, 2003 Abstract: The object of the present invention is to quantify glycated albumin, by providing means for providing quantification data, which correlate to the data of the quantification of glycated albumin by the HPLC method, without producing any intercept which might complicate use of the means in clinical medicine in a case where a
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regression curve is plotted by using the corrective quantification method with use of enzymes. Namely, the invention provides a method of detecting glycated albumin in the serum by using a reagent for assaying fructosamine, which comprises using a reagent for assaying glycated proteins by quantifying glycated proteins in the serum, correcting the value by dividing the thus-obtained value by the total albumin content in the serum and referring to the thus-corrected value as the glycated albumin content in the serum, wherein the method employs, as a glycated albumin standard, glycated albumin obtained from human blood by subjecting an albumin fraction originating in the blood of a healthy human to a treatment for distinguishing glycated albumin from non-glycated albumin. Excerpt(s): The present invention relates to a method of assaying a specific glycated protein in serum. Treatment of diabetes mellitus is desirably carried out on the basis of diagnosis performed as early and as accurately as possible. As one marker employable for diagnosis of diabetes mellitus, serum glycated albumin has become of interest as an index for short-term blood sugar assessment. Thus, a suitable method for assaying glycated albumin is currently under investigation. Presently, serum glycated albumin is determined by means of HPLC (Rinshokensa, vol. 40: 1275-1280, 1996). However, with HPLC, processing of a large number of specimens is difficult and operational cost is high. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and devices for preparing protein concentrates Inventor(s): Pathak, Chandrashekhar P.; (Austin, TX) Correspondence: Patterson, Thuente, Skaar & Christensen, P.A.; 4800 Ids Center; 80 South 80th Street; Minneapolis; MN; 55402-2100; US Patent Application Number: 20040002456 Date filed: February 11, 2003 Abstract: Materials, methods, and compositions for making crosslinked albumin hydrogels are included in the application. Embodiments include a biocompatible material of albumin crosslinked with an n-functional crosslinking agent wherein n is at least 3. Other embodiments include a cross-linking agent having a polyalkylene oxide member. Other embodiments include a system for administering an albumin material, the system having albumin and a crosslinking agent that reacts with the albumin to form a crosslinked material made of crosslinked albumin. Another embodiment is a method of making a biocompatible material that includes a step of mixing albumin with an n-functional crosslinking agent wherein n is at least 3. Excerpt(s): This application is a continuation-in-part of U.S. application serial No. 60/026,536 filed Sep. 23, 1996; U.S. application serial No. 60/039,904 filed Mar. 4, 1997 and U.S. application serial No. 60/040,417 filed Mar. 13, 1997, the disclosures of which are herein incorporated by reference. The field of the invention is the preparation of concentrated protein compositions. Methods of preparing concentrated protein compositions from initial dilute protein compositions find use in a variety of different industries, including the chemical, biological, academic research, biotechnological and medical industries. For example, "Fibrin Sealants" (also known as fibrin gels or fibrin glues) are a type of blood derived composition used in the medical industry which are prepared through methods of concentrating blood plasma proteins that have been developed for use as tissue adhesives, drug delivery vehicles and the like. Although
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such compositions are not yet FDA approved in the United States due to concerns over blood borne contaminants, such compositions are marketed in Europe and elsewhere throughout the world. A typical commercial fibrin glue kit consists of a vial of lyophilized concentrated human fibrinogen, prepared from pooled human donor blood, that also contains fibronectin, Factor XIII and reduced amounts of plasminogen. The concentrate, also known as cryoprecipitate, is reconstituted with a reconstituting solution and warmed to 37.sup.0 C The second component of the adhesive system is a lyophilized bovine thrombin solution which is reconstituted with a calcium chloride solution. The formulation may also contain additional components like a fibrionolysis inhibitor. The reconstituted solutions are mixed and used as a surgical adhesive system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for sterilizing preparations containing albumin Inventor(s): Burgess, Wilson; (Clifton, VA), Drohan, William N.; (Springfield, VA), Griko, Yuri; (Gaithersburg, MD), Kent, Randy; (Thousand Oaks, CA), Macphee, Martin J.; (Montgomery Village, MD), Mann, David; (Gaithersburg, MD), Miekka, Shirley I.; (Gaithersburg, MD) Correspondence: Fleshner & Kim, Llp; P.O. Box 221200; Chantilly; VA; 20153; US Patent Application Number: 20030213920 Date filed: August 31, 2001 Abstract: Methods are disclosed for sterilizing preparations containing albumin to reduce the level of one or more active biological contaminants or pathogens therein, such as viruses, bacteria (including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias), yeasts, molds, fungi, prions or similar agents responsible, alone or in combination, for TSEs and/or single or multicellular parasites. These methods involve sterilizing preparations containing albumin, such as plasma protein fractions, with irradiation. Excerpt(s): The present invention relates to methods for sterilizing preparations containing albumin to reduce the level of one or more active biological contaminants or pathogens therein, such as viruses, bacteria (including inter- and intracellular bacteria, such as mycoplasmas, ureaplasmas, nanobacteria, chlamydia, rickettsias), yeasts, molds, fungi, prions or similar agents responsible, alone or in combination, for TSEs and/or single or multicellular parasites. The present invention particularly relates to methods of sterilizing preparations containing albumin, such as plasma protein fraction (PPF) products, with irradiation. Albumin is a highly soluble, ellipsoidal protein (MW 66,500), accounting for 70-80% of the colloid osmotic pressure of plasma. Accordingly, albumin is important in regulating the volume of circulating blood. When injected intravenously, 5% albumin will increase the circulating plasma volume by an amount approximately equal to the volume infused. This extra fluid reduces hemoconcentration and decreases blood viscosity. The degree and duration of volume expansion depend upon the initial blood volume. When treating patients with diminished blood volume, the effect of infused albumin may persist for many hours. In individuals with normal blood volumes, the hemodilution lasts for a much shorter time. Albumin is also a transport protein and binds naturally occurring, therapeutic, and toxic materials in the circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Microencapsulated materials and method of making same Inventor(s): D'Souza, Martin J.; (Duluth, GA) Correspondence: Jason A. Bernstein; Bernstein & Associates, P.C.; Embassy Row 400, Suite 495; 6600 Peachtree Dunwoody Road, N.E.; Atlanta; GA; 30328-1649; US Patent Application Number: 20040043079 Date filed: August 29, 2002 Abstract: A method of forming microspheres of a bioactive material, such as a protein polymer or drug by nebulizing a solubilized form of a material to be encapsulated and an encapsulating material, such as albumin, in a stirred chilled solvent system comprising a vegetable oil, mineral oil and/or a lower alcohol such that the formed microspheres demonstrate intracellular bioactivity when taken up by macrophages. Excerpt(s): This application is a continuation-in-part of co-pending application U.S. application Ser. No. ______, filed Jun. 13, 2002, entitled "MICROENCAPSULATED COMPOUNDS AND METHOD OF PREPARING SAME", which is a continuation of application Ser. No. 08/434,542, filed May 4, 1995 (now abandoned), which is a continuation-in-part of application Ser. No. 07/977,057, filed Nov. 16, 1992 (now abandoned), all of which are commonly assigned to the assignee of the present application. The disclosures of all these applications are incorporated by reference in their entirety herein. The present invention relates to the field of drug delivery systems. Specifically, the present invention relates to methods for preparing microencapsulated drugs using non-antigenic, biodegradable materials and also to microencapsulated compositions that are targeted to phagocytic cells such as macrophages, endothelial cells, Kupffer cells, dendritic cells and the like, or a diseased organ (such as the liver, kidneys, lungs, heart, spleen), or a diseased site (such as tumors, arthritic joints), which digest the biodegradable coating, releasing the intact drug or active component either intracellularly or at the site of accumulation. Such compositions are useful in the treatment and prevention of diseases. Microencapsulation of water-soluble compounds contained in albumin microspheres ("MS") has been demonstrated by our laboratory (and disclosed in previous co-pending applications) to target phagocytic cells such as macrophages/monocytes, which produce the majority of the pro-inflammatory cytokines. This technique has been demonstrated to improve the efficacy of cytokine inhibiting compounds such as neutralizing antibodies. We have further evaluated the method of preparation of albumin microspheres containing other categories of drugs such as CNI-1493 (a guanylhydrazone compound which inhibits p38 MAP kinase), clodronate (a bisphosphonate), antioxidants such as pyrrolidine dithiocarbamate, and antisense oligomers to NF-kB. Microencapsulation of these compounds has improved inhibition of cytokines such as TNF, and IL1-beta in an in-vitro whole blood model, endotoxin shock model, and a bacterial septic shock model. We also have evaluated the preparation and completed the efficacy testing of a melanoma vaccine preparation, which worked very well in preventing tumors in mice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Microencapsulation of magentic material using heat stabilization Inventor(s): Chatterjee, Jhunu; (Tallahassee, FL), Chen, Ching-Jen; (Tallahassee, FL), Haik, Yousef; (Tallahassee, FL) Correspondence: Sutherland Asbill & Brennan Llp; 999 Peachtree Street, N.E.; Atlanta; GA; 30309; US Patent Application Number: 20040065969 Date filed: October 1, 2003 Abstract: Microencapsulation methods and products are provided. The method includes forming, at a first temperature, a emulsion which comprises aqueous microdroplets, including the agent (e.g., a magnetic material or drug) and a cross-linkable matrix material (e.g., a protein such as albumin), dispersed in a hydrophobic continuous phase comprising an oil and an oil-soluble surfactant, the first temperature being below the temperature effective to initiate cross-linking of the matrix material, and then heating the emulsion to a temperature and for a time effective to cause the matrix material to self-cross-link, to form microparticles comprising the agent encapsulated by the crosslinked matrix material. Excerpt(s): Priority is claimed to U.S. Provisional Application No. 60/415,493, filed Oct. 2, 2002. The application is incorporated herein by reference. This invention relates generally to micro- and nano-encapsulation methods, particularly for synthesizing magnetic microparticles, for use in biomedical or other applications. Chemically crosslinked materials have been used in to form microparticles. The cross-linkable material forming the matrix can be a synthetic polymer or a natural polymer or protein, for example. The microparticles formed with these materials have been used for biomedical applications, primarily in the areas of drug delivery, immunoassay, and cell separation technologies. Chatterjee, et al., J. Mag. Magn. Mat. 225:21 (2001) discloses a method of forming encapsulated particles by dissolving a polymer and a particular inorganic particle in an aqueous solvent, forming an oil-in-water emulsion, and stabilizing the particles using chemical cross-linking. The stabilization by chemical cross-linking can undesirably permit agglomeration. It therefore would be desirable to avoid using a chemical cross-linker in a process for forming microparticles. It would be particularly desirable to make such nanoparticles without requiring an emulsion polymerization reaction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Molecular press dehydration method for vegetative tissue using the solid phase of water soluble polymer substances as a dehydrating agent Inventor(s): Seo, Hyun-Chang; (Seoul, KR), Yoo, Myung-Shik; (Kyunggi-do, KR) Correspondence: Greenblum & Bernstein, P.L.C.; 1950 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20040062843 Date filed: June 23, 2003 Abstract: The present method is related to a molecular press dehydration method of vegetative tissues using water-soluble polymers in solid-phase as dehydrating agents. The molecular press dehydration method of the present invention is characterized by that dehydration is done by induction of cytorrhysis to vegetative tissues mixed with
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water-soluble polymers such as PEG, gum arabic, arabinogalactan, egg albumin, milk protein, soybean protein, etc. in its solid-phase. Compared to the conventional dehydration methods, the present method enables to obtain much greater dehydration effects in the amount and the rate, even though a very small amount of polymer substance is used; and the method enables to obtain excellent quality of dehydrated tissues as well as dehydrated exudates; and is environmentally friendly under favor of reduced energy consumption. The dehydrated vegetative tissues are excellent in their storage stability, and flavor and texture after rehydration, and dehydrated exudates are excellent in the concentrated useful components, flavor, and preservation quality. Therefore, the dehydrated vegetative tissues and exudates obtained by using the dehydration method of the present invention may be usefully applied to various fields such as foods and beverages, feeds, cosmetics, medicines, flavorings, agricultural chemicals, coloring agents, etc. according to the characteristics of plants. Excerpt(s): The present invention is related to a molecular press dehydration method of vegetative tissues. Dehydration of vegetables is a very useful technology for the manufacture and development of foods and beverages, feeds, cosmetics, and pharmaceuticals. Traditional dehydration and drying methods of vegetative tissues include osmotic dehydration, hot-air drying, freeze drying, etc. In osmotic dehydration, water of hypotonic solution in cytoplasms transfers to the hypertonic solution of a dehydrating agent through semipermeable cell membranes. In this method, immersion of vegetables into the concentrated dehydrating solution induces dehydration by the gradients of concentration between cell membranes. Included in this method are salting using salts such as the table salt, etc. and sugaring using sugars such as sucrose, etc. as dehydrating agents. This method is advantageous in that the initial dehydration rate is high. However, it is disadvantageous in that the final amount of dehydration is small because most of transferred water remains in the cell wall by rapid shrinking and destruction of cell membranes, and dehydration is stopped immediately after the dehydrating agent is diffused into the cell wall and there is no difference in the concentrations of dehydrating agents in and out of the cells. Also, a large amount of the dehydrating agent penetrated into the cell wall reduces the rate of drying after dehydration due to a lowered water activity by the solute of the dehydrating agent, and it affects the taste of dehydrated tissues adversely, and lowers rehydration quality of tissues after drying as the dehydrating agent denatures cell wall components during dehydration. Further, the quality of tissues is lowered as useful components of dehydrated tissues are reduced since a large amount of cell fluid components flows out of the cells due to destruction of cell membranes during dehydration. Therefore, this method is used for the preservation of dehydrated tissues with a dehydrating agent as in salting or sugaring, reducing the dehydration time, and partially as the pre-step of drying for improving the quality of dried tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel cocoa albumin and its use in the production of cocoa and chocolate flavor Inventor(s): Hansen, Carl Eric; (Epalinges, CH), Juillerat, Marcel Alexandre; (Lausanne, CH), Kochhar, Sunil; (Savigny, CH), McCarthy, James; (Noizay, FR) Correspondence: Winston & Strawn; Patent Department; 1400 L Street, N.W.; Washington; DC; 20005-3502; US Patent Application Number: 20040010123 Date filed: May 21, 2003
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Abstract: The present invention is directed to a novel 2S cocoa albumin protein that has now been isolated, purified and identified from cocoa beans. The present invention is further directed to flavor precursors generated from the enzymatic hydrolysis of this novel protein and to use of the flavor precursors to form a cocoa flavor useful in making chocolate flavored compositions. Excerpt(s): This application is a continuation of the US national stage designation of International Application PCT/EP01/13536 filed Nov. 21, 2001, which claims priority to European patent application 00125523.1 filed Nov. 21, 2000, the disclosures of both of which are incorporated herein by express reference thereto. The present invention relates to a novel cocoa polypeptide and the nucleic acid sequence encoding it. In particular, the present invention pertains to the use of said polypeptide and/or flavor precursor fragments thereof in the production of chocolate flavor and for use in making chocolate flavored compositions. In processing cocoa beans the generation of the typical cocoa flavor requires two steps, the fermentation step and the roasting step. During fermentation the pulp surrounding the beans is degraded by micro-organisms with the sugars contained in the pulp being essentially transformed to acids. Fermentation also results in a release of peptides exhibiting differing sizes and a generation of a high level of free hydrophobic amino acids. This latter finding led to the hypothesis that proteolysis occurring during fermentation is not due to a random protein hydrolysis but seems to be rather based on the activity of specific endoproteinases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel use of arylethene sulfonamide derivative Inventor(s): Fujimori, Akira; (Ibaraki, JP), Shibasaki, Kumiko; (Tsukuba-shi, JP), Sonoda, Rie; (Tsukuba-shi, JP), Tahara, Atsuo; (Tsukuba-shi, JP), Yuyama, Hironori; (Ibaraki, JP) Correspondence: Finnegan Henderson Farabow; Garrett & Dunner; 1300 I Street NW; Washington; DC; 20005-3315; US Patent Application Number: 20040097529 Date filed: September 26, 2003 Abstract: Novel use of N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2yl)pyrimidin- -4-yl]-2-phenylethenesulfonamide or a pharmaceutically acceptable salt thereof. Improvement of the following particular condition in a diabetic patient: (1) Elevation of blood glucose level; (2) Elevation of blood lipid level after the onset of early-stage nephropathy; (3) Renal dysfunction after the onset of early-stage nephropathy; (4) Increase of urinary albumin excretion after the onset of early-stage nephropathy; (5) Glomerular hyperfiltration after the onset of early-stage nephropathy; (6) Renal dysfunction after the progress toward chronic renal failure; (7) Increase of urinary protein excretion after the progress toward chronic renal failure. Excerpt(s): The present invention relates to novel use of N-[6-methoxy-5-(2methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2 -phenylethenesulfonamide or salts thereof. Endothelin (hereinafter referred to as "ET") is an endogenous physiologically active peptide consisting of 21 amino acids, and known to exist as 3 types of iso-peptides, i.e., ET-1, ET-2 and ET-3, of which the amino acid sequences are slightly different each other. ET binds to the ET receptor on the target cellular membrane to exhibit a physiological activity. Up to now, as for the ET receptor, it is known that there are at least 2 sub-types, i.e., ET.sub.A and ET.sub.B. ET.sub.A receptor has higher affinity to ET-1 and ET-2 than to ET-3, and ETB receptor has the same degree
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of affinity to ET-1, ET-2 and ET-3. N-[6-Methoxy-5-(2 -methoxyphenoxy)-2-(pyrimidin-2yl)pyrimidin-4-yl- ]-2-phenylethenesulfonamide (hereinafter referred to as "Compound A") or salts thereof have been disclosed in International Patent Publication No. 97/22595, in which their effect of inhibiting the binding of ET-1 to the ET.sub.A receptor as well as the effect of inhibiting the ET-1-induced vasoconstriction and elevation of blood pressure have been disclosed specifically, but there is no disclosure on other particular effect. On the other hand, a number of diseases in which ET is possibly involved have been exemplified as follows: essential hypertension, pulmonary hypertension, erythropoietin-induced hypertension, cyclosporin A-induced hypertension, bronchial asthma, acute renal failure, chronic renal failure, glomerular nephritis, cyclosporin-induced renal failure, acute myocardial infarction, unstable angina pectoris, chronic heart failure, cerebrovascular spasm mainly caused by subarachnoid hemorrhage, cerebral ischemic disturbance, urinary incontinence, benign prostatic hypertrophy, arteriosclerosis, Raynaud's syndrome, diabetic peripheral circulatory disturbance, diabetic nephropathy, preeclampsia, premature labor, peptic ulcer, hepatic insufficiency, rheumatism, restenosis after PTCA, chronic respiratory failure, chronic obstructive pulmonary disease, cor pulmonale, acute respiratory failure, pulmonary edema, ischemic hepatopathy, adult respiratory distress syndrome, interstitial pneumonia, fibroid lung, glaucoma, osteoarthritis, chronic rheumatoid arthritis, liver cirrhosis, inflammatory enteropathy, cancer, and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pancreatic progenitor cells and methods for isolating the same Inventor(s): Krakowski, Michelle L.; (Del Mar, CA), Kritzik, Marcie R.; (La Jolla, CA), Sarvetnick, Nora; (San Diego, CA) Correspondence: Ivor R. Elrifi; Mintz Levin; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20040058398 Date filed: September 26, 2003 Abstract: The invention provides animal models, where the ectopic expression of KGF, EGF, or both is under the control of a pancreas-specific promoter, e.g., the insulin promoter. The expression of KGF in the ins-KGF pancreatic islets of Langerhans results in enlarged islets, with substantial proliferation of duct cells within the islet mass, and the presence of albumin and alpha-fetoprotein-producing hepatocytes in the islets of the ins-KGF pancreata. The compositions and methods disclosed are useful for identifying and isolating pancreatic stem/progenitor cells, including a common stem/progenitor to liver cells and pancreatic cells. Excerpt(s): This invention relates to generally to models for identifying and isolating pancreatic stem cells, and in one embodiment, to models for identifying and isolating a common stem/progenitor cell that gives rise to hepatic cells and pancreatic cells. A healthy adult pancreas is usually a developmentally stable organ, but a targeted cell loss or aberrant cell growth and development have pathological consequences. For example, in human Insulin Dependent Diabetes Mellitus (IDDM), autoimmune mechanisms cause the selective and permanent destruction of the insulin-producing beta cells in the islets of Langerhans The lost cells are not restored in vivo, although Sarvetnick et al. Cell 52:773-782 , (1988) have shown that beta cells have the potential to regenerate. On the other hand, the proliferation of duct cells can contribute to pancreatic disease pathologies, such as chronic pancreatitis, pancreatic cancer, and cystic fibrosis.
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Pancreatic duct cell proliferation and differentiation have also been shown by Arnush et al., Lab Invest 74: 985-990 (1995) to play a critical role in a transgenic mouse model of islet regeneration. Further, endocrine cell differentiation is frequently seen in pancreatic duct cell carcinomas, suggesting that duct cell proliferation can lead to islet neogenesis. Growth factors are critical for modulating cellular proliferation and differentiation. The growth factors that regulate and promote pancreatic growth are not well characterized, but keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is known to be involved in wound healing and in the differentiation of many epithelial tissues. KGF upregulates epithelial cell proliferation and pancreatic duct cell proliferation in rats. Also, epidermal growth factor (EGF) and transforming growth factor beta-1(TGF.beta.-1) can induce ductal and endocrine cell development, respectively. EGF, which is known to stimulate epithelial cell and fibroblast proliferation, also has mitogenic properties for pancreatic growth. The overexpression of EGF and EGF receptor (EGF-R) is linked both to chronic pancreatitis and to malignant pancreatic growth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical proteins, human therapeutics, human serum albumin, insulin, native cholera toxic b submitted on transgenic plastids Inventor(s): Daniell, Henry; (Winter Park, FL) Correspondence: Schnader Harrison Segal & Lewis; IP Department 36th Floor; 1600 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20030204864 Date filed: April 18, 2001 Abstract: Transgenic chloroplast technology could provide a viable solution to the production of Insulin-like Growth Factor I (IGF-I), Human Serum Albumin (HSA), or interferons (IFN) because of hyper-expression capabilities, ability to fold and process eukaryotic proteins with disulfide bridges (thereby eliminating the need for expensive post-purification processing). Tobacco is an ideal choice because of its large biomass, ease of scale-up (million seeds per plant), genetic manipulation and impending need to explore alternate uses for this hazardous crop. Therefore, all three human proteins will be expressed as follows: a) Develop recombinant DNA vectors for enhanced expression via tobacco chloroplast genomes b) generate transgenic plants c) characterize transgenic expression of proteins or fusion proteins using molecular and biochemical methods d) large scale purification of therapeutic proteins from transgenic tobacco and comparison of current purification/processing methods in E. coli or yeast e) Characterization and comparison of therapeutic proteins (yield, purity, functionality) produced in yeast or E. coli with transgenic tobacco f) animal testing and pre-clinical trials for effectiveness of the therapeutic proteins.Mass production of affordable vaccines can be achieved by genetically engineering plants to produce recombinant proteins that are candidate vaccine antigens. The B subunits of Enteroxigenic E. coli (LTB) and cholera toxin of Vibrio cholerae (CTB) are examples of such antigens. When the native LTB gene was expressed via the tobacco nuclear genome, LTB accumulated at levels less than 0.01% of the total soluble leaf protein. Production of effective levels of LTB in plants, required extensive codon modification. Amplification of an unmodified CTB coding sequence in chloroplasts, up to 10,000 copies per cell, resulted in the accumulation of up to 4.1% of total soluble tobacco leaf protein as oligomers (about 410 fold higher expression levels than that of the unmodified LTB gene). PCR and Southern blot analyses confirmed
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stable integration of the CTB gene into the chloroplast genome. Western blot analysis showed that chloroplast synthesized CTB assembled into oligomers and was antigenically identical to purified native CTB. Also, GM.sub.1,-ganglioside binding assays confirmed that chloroplast synthesized CTB binds to the intestinal membrane receptor of cholera toxin, indicating correct folding and disulfide bond formation within the chloroplast. In contrast to stunted nuclear transgenic plants, chloroplast transgenic plants were morphologically indistinguishable from untransformed plants, when CTB was constitutively expressed. The introduced gene was stably inherited in the subsequent generation as confirmed by PCR and Southern blot analyses. Incrased production of an efficient transmucosal carrier molecule and delivery system, like CTB, in transgenic chloroplasts makes plant based oral vaccines and fusion proteins with CTB needing oral administration a much more practical approach. Excerpt(s): (60/115,987) Research efforts have been made to synthesize high value pharmacologically active recombinant proteins in plants. Recombinant proteins such as vaccines, monoclonal antibodies, hormones, growth factors, neuropeptides, cytotoxins, serum proteins and enzymes have been expressed in nuclear transgenic plants (May et al., 1996). It has been estimated that one tobacco plant should be able to produce more recombinant protein than a 300-liter fermenter of E. coli. In addition, a tobacco plant produces a million seeds, thereby facilitating large-scale production. Tobacco is also an ideal choice because of its relative ease of genetic manipulation and an impending need to explore alternate uses for this hazardous crop. (60/185,987) A primary reason for the high cost of production via fermentation is the cost of carbon source co-substances as well as maintenance of a large fermentation facility. In contrast, most estimates of plant production are a thousand-fold less expensive than fermentation. Tissue specific expression of high value proteins in leaves can enable the use of crop plants as renewable resources. Harvesting the cobs, tubers, seeds or fruits for food and feed and leaves for value added products should result in further economy with no additional investment. (60/185,987) However, one of the major limitations in producing pharmaceutical proteins in plants is their low level of foreign protein expression, despite reports of higher level expression of enzymes and certain proteins. May et al. (1998) discuss this problem using the following examples. Although plant derived recombinant hepatitis B surface antigen was as effective as a commercial recombinant vaccine, the levels of expression in transgenic tobacco were low (0.01% of total soluble protein). Even though Norwalk virus capsid protein expressed in potatoes caused oral immunization when consumed as food (edible vaccine), expression levels were low (0.3% of total soluble protein). A synthetic gene coding for the human epidermal growth factor was expressed only up to 0.001% of total soluble protein in transgenic tobacco. Human serum albumin has been expressed only up to 0.02% of the total soluble protein in transgenic plants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preparation and xenotransplantation or porcine islets Inventor(s): Basta, Guiseppe; (Dimisem Perugia, IT), Calafiore, Riccardo; (Dimisem Perugioa, IT), Elliott, Robert Bartlett; (Auckland, NZ), Luca, Giovanni; (Dimisem Perugia, IT) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20040014212 Date filed: June 25, 2003 Abstract: The invention relates to a method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising: (i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, (iii) the culture of the harvested pancreas being a) of mechanically reduced harvested pancreas, and b) a supportive mammalian albumin substantially free of non-human microbiological agents,wherein (at least some stage in the method) the islets are associated with Sertoli cells. The preparations is preferably used in one of two implantation devices, the method of preparation of which are disclosed: a vascularised subcutaneous collagen tube, a capsule formed from a biocompatible xenotransplantable material Further disclosed are methods of treating a mammalian patient predisposed to or suffering from diabetes which involves the xenotransplantation into such patient an implantation device of the invention. Excerpt(s): The present invention relates to improvements in and/or relating to the treatment of diabetes using xenotransplantation. More particularly but not exclusively the present invention relates to the preparation of viable xenotransplantable porcine islets and/or the treatment of a mammalian patient (including humans) suffering from diabetes involving the transplantation into the mammal of viable porcine islets capable of producing insulin within the host and the associated use of sertoli cells within the procedure. Type 1 (insulin-dependent) diabetes mellitus is a common endocrine disorder that results in substantial morbidity and mortality, and leads to considerable financial costs to individual patients and healthcare systems. Treatment with insulin, while life-saving, often does not provide sufficient control of blood glucose to prevent the feared complications of the disease, which has provided the impetus for intensive research into better methods of sustaining normoglycaemia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for the purification of serum albumin Inventor(s): Johannes Piet, Marcellinus Petrus; (Haarlem, NL), Van Der Laken, Cornelis Jacobus; (Leiden, NL) Correspondence: Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20030204060 Date filed: December 30, 2002 Abstract: Recombinantly produced serum albumin is purified in a series of steps, optionally by incubation with an anion-exchange adsorbent, followed by affinity
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chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase. Said immobile phase comprises a carrier coupled to a 2-mercapto or 2-hydroxy alkanoic acid. Excerpt(s): The field concerns purification of serum albumins, particularly human serum albumins. Human serum albumin (HSA) is the major protein component of plasma. The primary function of albumin in plasma is maintenance of the colloid osmotic pressure within the blood vessel. Furthermore, the protein acts as a carrier of several ligands, for instance bilirubin and fatty acids. (See reviews by F. Rothstein, V. M. Rosenoer and W. L. Hughes in Albumin Struct. Funct. Uses (1977) 7-25; U. Kragh-Hansen, Pharmacol. Rev. (1981) 33:17-53; T. Peters Jr., Adv. Prot. Chem. (1985) 37:161-245). Purified serum albumin is indicated for the prevention and treatment of hypovolemic shock, in conditions where there is severe hypoalbuminemia, as an adjunct in haemodialysis and in cardiopulmonary bypass procedures and in conjunction with exchange transfusion in the treatment of neonatal hyperbilirubinemia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process of high purity albumin production Inventor(s): Berezenko, Stephen; (Hucknall, GB), Burton, Stephen James; (Little Eversden, GB), Goodey, Andrew Robert; (Mapperley Park, GB), Johnson, Richard Alan; (West Bridgford, GB), Quirk, Alan Victor; (Loughborough, GB), Sleep, Darrell; (West Bridgford, GB), Van Urk, Hendrik; (Radcliffe-on-Trent, GB), Wood, Patricia Carol; (Burton-Trent, GB), Woodrow, John Rodney; (West Bridgford, GB) Correspondence: Naomi Biswas; Centeon L.L.C.; 1020 First Avenue; King OF Prussia; PA; 19406-1310; US Patent Application Number: 20030187226 Date filed: November 21, 2002 Abstract: A process is provided for the preparation of albumin which has extremely low levels of or is essentially free of colorants, metal ions, human proteins, host proteins, fragments of albumin, polymers or aggregates of albumin and viruses, and which is essentially non-glycated, relatively high in free thiol and with an intact C-terminus. The process comprises passing albumin (preferably expressed and secreted by transformed yeast) through positive mode cation exchange and then positive mode anion exchange chromatography. Other steps may also be employed, for example ultrafiltration, gel permeation chromatography, affinity chromatography binding the albumin (for example using blue dyes) and affinity chromatography binding contaminants (for example using an aminophenylboronic acid resin). Elution of albumin, with a compound having affinity for albumin, from a material having no specific affinity for albumin is also disclosed, as is removal of ammonium ions with a counter-ion. Excerpt(s): This application is a continuation of U.S. application Ser. No. 08/952,558, which is a continuation-in-part of U.S. application Ser. No. 08/378,859, filed May 25, 1995, the contents of which are hereby incorporated herein by reference. The present invention relates to purifying the protein human serum albumin (HSA) extracted from serum or recombinant human albumin (rHA) produced by transforming a microorganism with a nucleotide coding sequence encoding the amino acid sequence of human serum albumin. In this specification, the term Aalbumin.congruent.refers generically to HSA and/or rHA. Albumin is used to treat patients with severe burns, shock or blood loss. It is also used to supplement media used for growing higher
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eukaryotic cells and as an excipient in the formulation of therapeutic proteins. At present, the demand for the product is satisfied by albumin extracted from human blood. Examples of extraction and separation techniques include those disclosed in: JP 03/258 728 on the use of a cation exchanger; EP 428 758 on the use of anion exchange followed by cation exchange; and EP 452 753 on the use of heating, adding salt and diafiltering. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Proliferation of hepatocyte precursors Inventor(s): Agelli, Maria; (Summit, NJ), Ochs, Andreas; (Bronx, NY), Reid, Lola M.; (Chapel Hill, NC) Correspondence: Patent Adminstrator; Katten Muchin Zavis Rosenman; 525 West Monroe Street; Suite 1600; Chicago; IL; 60661-3693; US Patent Application Number: 20040037814 Date filed: August 22, 2003 Abstract: A composition which comprises an animal cell population which contains immature animal cells. The immature animal cells are characterized by expression of alpha-fetoprotein or lack of essential expression of alpha-fetoprotein and albumin, and at least a portion of said immature animal cells or at least a portion of the progeny of said immature animal cells is capable of differentiating into cells which express albumin. The cell population is cultured under conditions which result in expansion of the cells. Expansion of the cells may be achieved by culturing the cells in the presence of an extracellular matrix and liver stromal cells; and preferably in the presence of growth factors. Such cells may be used for liver transplantation, artificial livers, and for toxicology and pharmacology studies. Such cells may also be genetically engineered to express proteins or polypepetides of interest. Excerpt(s): This invention relates to the expansion, or proliferation of cells and in particular cells whose progeny may differentiate into mature hepatocytes. More particularly, this invention relates to the enrichment of, and to the expansion or proliferation of such cells in the presence of stromal cells, an extracellular matrix, and/or growth factors. In another aspect, this invention relates to genetically engineered cells which are capable of differentiating into hepatocytes. In accordance with an aspect of the present invention, there is provided a composition which comprises an animal cell population. The cell population contains immature cells (i) at least a portion of said cells or a portion of the progeny of said cells is capable of differentiating into hepatocytes and (ii) which are characterized by expression of alpha-fetoprotein or lack of essential expression of alpha-fetoprotein and albumin, and at least a portion of said cells or of the progeny of said cells is capable of differentating into cells which express albumin. In general, the differentiated cells which express albumin have morphological and physiological characteristics of mature hepatocytes. The cell population has been cultured under conditions which result in expansion of the immature cells. Such cells are sometimes hereinafter referred to as "hepatocyte precursors". The hepatocyte precursors may be derived from any animal, preferably from mammals. Mammals from which the hepatocyte precursors may be derived include, but are not limited to, humans, rodents (e.g., rats, mice, hamsters), rabbits, bovines, horses, pigs, and sheep. Preferably, the hepatocyte precursors are derived from humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Recombinant human albumin fusion proteins with long-lasting biological effects Inventor(s): Fu, Yan; (Baltimore, MD), Yu, Zailin; (Baltimore, MD) Correspondence: Fortunerock INC.; Attn: DR. Zailin YU; APT. D109; 3120 Saint Paul ST.; Baltimore; MD; 21218; US Patent Application Number: 20040063635 Date filed: June 26, 2003 Abstract: Compositions, kits and methods are provided for promoting general health or for prevention or treatment of diseases by using novel recombinant fusion proteins of human serum albumin (HSA) and bioactive molecules. The bioactive molecules may be a protein or peptide having a biological function in vitro or in vivo, and preferably, having a therapeutic activity when administered to a human. By fusing the bioactive molecule to HSA, stability of the bioactive molecule in vivo can be improved and the therapeutic index increased due to reduced toxicity and longer-lasting therapeutic effects in vivo. In addition, manufacturing processes are provided for efficient, costeffective production of these recombinant proteins in yeast. Excerpt(s): This application claims the priority benefit of U.S. Provisional Application Serial No: 60/392,948 filed Jul. 1, 2002, which is hereby incorporated herein by reference in its entirety. This invention relates to the manufacture and use of recombinant albumin fusion proteins and combinations thereof, and particularly to yeast expressed fusion proteins formed between human albumin and bioactive molecules such as therapeutic proteins and peptides, and more particularly to yeast expressed fusion proteins formed between human albumin and cell proliferation stimulatory factor (CPSF), such as, blood cell-stimulatory factors, erythropoietin (EPO), interleukins (ILs), stem cell factor (SCF), thrombopoietin (TPO), granulocyte colony stimulating factor (GCSF), and granulocyte macrophage colony stimulating factor (GM-CSF). Albumin is a soluble, monomeric protein which comprises about one-half of the blood serum protein. Albumin functions primarily as a carrier protein for steroids, fatty acids, and thyroid hormones and plays a role in stabilizing extracellular fluid volume. Mutations in this gene on chromosome 4 result in various anomalous proteins. Albumin is a globular unglycosylated serum protein of molecular weight 65,000. The human albumin gene is 16,961 nucleotides long from the putative `cap` site to the first poly(A) addition site. It is split into 15 exons which are symmetrically placed within the 3 domains that are thought to have arisen by triplication of a single primordial domain. Albumin is synthesized in the liver as pre-pro-albumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin. HSA has 35 cysteins; in blood this protein monomer has 17 disulfide linkage (Brown, J. R. "Albumin structure, Function, and Uses" Pergamon, New York, 1977). HSA is misfolded when produced intracellularly in yeast without its amino terminal secretion peptide sequence. This conclusion is based on its insolubility, loss of great than 90% of its antigenicity (as compared to human-derived HSA), and formation of large protein aggregates. At present albumin for clinical use is produced by extraction from human blood. The production of recombinant albumin in microorganisms has been disclosed in EP 330 451 and EP 361 991. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Serum albumin binding peptides for tumor targeting Inventor(s): Dennis, Mark S.; (San Carlos, CA) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20040001827 Date filed: June 28, 2002 Abstract: Peptide ligands having affinity for serum albumin are useful for tumor targeting. Conjugate molecules comprising a serum albumin binding peptide fused to a biologically active molecule demonstrate modified pharmacokinetic properties as compared with the biologically active molecule alone, including tissue (e.g., tumor) uptake, infiltration, and diffusion. Excerpt(s): This invention relates to compounds comprising a peptide ligand domain and an active domain, useful, for example, as therapeutic and diagnostic agents. In particular, hybrid molecules comprising a peptide ligand domain that binds serum albumin and a active domain, such as a biologically active molecule, are useful as tumor targeting agents, having altered pharmacokinetic and pharmacological properties as compared to the active domain alone. Therapeutic methods for the treatment of disease rely on the administration of a therapeutic molecule to a patient, the distribution of the administered therapeutic in the body, generally via blood circulation, and the uptake and efficacy of the administered drug at the target tissue. The effectiveness of an administered protein depends heavily on upon the intrinsic pharmacokinetics of the molecule, for example, protein. Generally, high doses are utilized to offset rapid and efficient clearance of such molecules, for example, protein therapeutics from the circulation, including degradation mechanisms. As a consequence, the amount of time that the therapeutic molecule is exposed to the desired tissue may be short, reducing possible therapeutic effects. Several parameters can be addressed to improve efficacy and efficiency of an administered therapeutic molecule. These include increasing halflife, increasing uptake into tissue, and increasing diffusion of the molecule into tissue. Decreasing the size of the molecule, for example, administering a Fab fragment rather than a fulisize IgG molecule, improves two of these parameters, tissue uptake and diffusion. However, decreased size is also associated with more rapid clearance and reduced half-life. See, for example, Adams et.al., 1999, J. Immunol. Methods 231:249-260. For most applications, these parameters must be balanced, so that optimization of one factor does not lead to difficulties with another. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Serum protein-associated target-specific ligands and identification method therefor Inventor(s): Edge, Albert; (Newton, MA), Sato, Aaron K.; (Somerville, MA) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20040071705 Date filed: June 23, 2003 Abstract: Disclosed is an artificial target-specific ligand that binds to both serum albumin and a particular molecular target. Interaction with serum albumin improves properties when administered to a subject. For example, an interaction between the ligand and serum albumin can extend the half-life of the ligand in circulation.
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Excerpt(s): This application claims priority to U.S. application Ser. No. 60/390,657, filed on Jun. 21, 2002, the contents of which are incorporated by reference in their entirety for all purposes. Serum albumin is an abundant transport protein of approximately 70 kiloDaltons in circulating blood of mammalian species. For example, serum albumin is normally present at a concentration of approximately 3 to 4.5 grams per 100 ml of whole blood. Serum albumin provides several important functions in the circulatory system. For instance, it functions as a transporter of a variety of organic molecules found in the blood, as the main transporter of various metabolites such as fatty acids, hematin, and bilirubin, and, owing to its abundance, as an osmotic regulator of the circulating blood. It also has a broad affinity for small, negatively charged aromatic compounds. These binding functions enable serum albumin to serve as the principal carrier of fatty acids that are otherwise insoluble in circulating plasma. Serum albumin can also bind to drugs that are administered to a subject. Indeed, one indicator of the efficacy of a drug is its affinity for serum albumin or other serum proteins. Binding to serum albumin can affect the overall distribution, metabolism, and bioavailability of many drugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Simple methods for the drug monitoring of gpiib/iiia-receptor antagonists Inventor(s): Bucha, Elke; (Erfurt, DE), Nowak, Gotz; (Erfurt, DE) Correspondence: Kagan Binder, Pllc; Suite 200, Maple Island Building; 221 Main Street North; Stillwater; MN; 55082; US Patent Application Number: 20040029193 Date filed: August 7, 2003 Abstract: The invention relates to the use of monodisperse polymer particles of human albumin, fibrin, fibrinogen or polyphenylmethacrylate for quantitative measuring of the adhesion of platelets in vitro. Excerpt(s): The thrombogenicity of arterial occlusive diseases and the predisposition thereof is determined by means of pathological platelet reactions. The blood plateletdirected starter reaction for manifest arterial macro and micro thromboses is focus for a range of drug developments. In recent years, the therapeutic principle of blocking GPIIb/IIIa receptors of platelets has shown to be particularly promising. In various studies (Capture, Epilog, Epic, Epistent and others), it could be demonstrated without doubt that a thrombotic reaction can be prevented or antagonised by means of substances obstructing fibrinogen receptors of the platelets (GPIIb/IIIa). So far, the greatest experience has been gained with a monoclonal antibody fragment, the so-called Abciximab (Reopro), but also further substances from other sources, such as natural disintegrines or peptide antagonists or peptidomimetica are being subjected to clinical examination at present. In practice, the essential problem with these substances is the fact that they exhibit clinical efficiency only when 60-80% of the GPIIb/IIIa receptors of all platelets in circulation are blocked. The extremely low therapeutic index of these substances is to be explained by the fact that already at 90-95% receptor blocking, there is an excessive bleeding tendency. This severe side effect also limits a broad application of this new substance group. In the past, there were plenty of attempts to control the blood level by means of the most varied methods determining the function of the platelets. However, there is no correlation between the blood level of the GPIIb/IIIa antagonists and the effect, since there is no direct relationship between the height of the substance blood level and the strength of the aggregation inhibition. This lack of correlation is, above all, due to the variable number of circulating platelets but also the
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number of the integrin molecules exposed at the platelet surface. Mostly, methods for measuring the platelet aggregation are used for the detection of the efficacy. The aggregation agonists reactions carried out in plasma containing platelets or platelet-rich plasma for collagenes or ADP are time-consuming and costly and show the real conditions in the blood of the patient only indirectly, since they do not allow reactions that are identical to natural reactions due to the obligatory separation and enrichment of the plasma of the patient with blood platelets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tests for the rapid evaluation of ischemic states and kits Inventor(s): Bar-Or, David; (Englewood, CO), Lau, Edward; (Boulder, CO), Winkler, James V.; (Denver, CO) Correspondence: Swanson & Bratschun L.L.C.; 1745 Shea Center Drive; Suite 330; Highlands Ranch; CO; 80129; US Patent Application Number: 20030190691 Date filed: April 15, 2003 Abstract: The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue. Excerpt(s): The subject application is a divisional of co-pending U.S. Ser. No. 09/806,247, filed Oct. 1, 1999; which is a 35 USC 371 of PCT/US/22905, filed Oct. 1, 1999, which is a continuation-in-part of U.S. Ser. No. 09/165,581, filed Oct. 2, 1998, now U.S. Pat. No. 6,492,179; and a continuation-in-part of U.S. Ser. No. 09/165,926, filed Oct. 2, 1998, now U.S. Pat. No. 6,461,875. The foregoing cases are all incorporated by reference in their entirety. The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. More particularly, the invention relates to the measurement of a bound specific transition element to human serum albumin or the measurement of albumin N-terminal derivatives to determine the presence or absence of ischemia. Ischemia is the leading cause of illness and disability in the world. Ischemia is a deficiency of oxygen in a part of the body causing metabolic changes, usually temporary, which can be due to a constriction or an obstruction in the blood vessel supplying that part. The two most common forms of ischemia are cardiovascular and cerebrovascular. Cardiovascular ischemia, in which the body's capacity to provide oxygen to the heart is diminished, is the leading cause of illness and death in the United States. Cerebral ischemia is a precursor to cerebrovascular accident (stroke) which is the third leading cause of death in the United States. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of thiol redox proteins for reducing protein intramolecular disulfide bonds, for improving the quality of cereal products, dough and baked goods and for inactivating snake, bee and scorpion toxins Inventor(s): Buchanan, Bob B.; (Berkeley, CA), Jiao, Jin-An; (Miami, FL), Kobrehel, Karoly; (Montpellier, FR), Lozano, Rosa M.; (Madrid, ES), Shin, Sungho; (Taejon, KR), Wong, Joshua H.; (San Francisco, CA), Yee, Boihon C.; (Walnut Creek, CA) Correspondence: Morrison & Foerster Llp; 425 Market Street; San Francisco; CA; 941052482; US Patent Application Number: 20030215542 Date filed: June 17, 2003 Abstract: Methods of reducing cystine containing animal and plant proteins, and improving dough and baked goods' characteristics is provided which includes the steps of mixing dough ingredients with a thiol redox protein to form a dough and baking the dough to form a baked good. The method of the present invention preferably uses reduced thioredoxin with wheat flour which imparts a stronger dough and higher loaf volumes. Methods for reducing snake, bee and scorpion toxin proteins with a thiol redox (SH) agent and thereby inactivating the protein or detoxifying the protein in an individual are also provided. Protease inhibitors, including the Kunitz and BowmanBirk trypsin inhibitors of soybean, were also reduced by the NADP/thioredoxin system (NADPH, thioredoxin, and NADP-thioredoxin reductase) from either E. coli or wheat germ. When reduced by thioredoxin, the Kunitz and Bowman-Birk soybean trypsin inhibitors lose their ability to inhibit trypsin. Moreover, the reduced form of the inhibitors showed increased susceptibility to heat and proteolysis by either subtilisin or a protease preparation from germinating wheat seeds. The 2S albumin of castor seed endosperm was reduced by thioredoxin from either wheat germ or E. coli. Thioredoxin was reduced by either NADPH and NADP-thioredoxin reductase or dithiothreitol. Analyses showed that thioredoxin actively reduced the intramolecular disulfides of the 2S large subunit, but was ineffective in reducing the intermolecular disulfides that connect the large to the small subunit. A novel cystine containing protein that inhibits pullulanase was isolated. The protein was reduced by thioredoxin and upon reduction its inhibitory activity was destroyed or greatly reduced. Excerpt(s): This application is a continuation-in-part of application of Ser. No. 07/935,002, filed Aug. 25, 1992 which is a continuation-in-part application of Ser. No. 07/776,109, filed Oct. 12, 1991. The present invention relates to the use of thiol redox proteins to reduce seed protein such as cereal proteins, enzyme inhibitor proteins, venom toxin proteins and the intramolecular disulfide bonds of certain other proteins. More particularly, the invention involves use of thioredoxin and glutaredoxin to reduce gliadins, glutenins, albumins and globulins to improve the characteristics of dough and baked goods and create new doughs and to reduce cystine containing proteins such as amylase and trypsin inhibitors so as to improve the quality of feed and cereal products. Additionally, the invention involves the isolation of a novel protein that inhibits pullulanase and the reduction of that novel protein by thiol redox proteins. The invention further involves the reduction by thioredoxin of 2S albumin proteins characteristic of oil-storing seeds. Also, in particularly the invention involves the use of reduced thiol redox agents to inactivate snake neurotoxins and certain insect and scorpion venom toxins in vitro and to treat the corresponding toxicities in individuals. (Florencio F. J., et al. (1988), Arch. Biochem. Biophys. 266:496-507; Johnson, T. C., et al. (1987), Plant Physiol. 85:446-451; Suske, G., et al. (1979), Z. Naturforsch. C. 34:214-221). Current evidence suggests that the cohesiveness to dough. Gluten is composed mostly
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of the gliadin and glutenin proteins. It is formed when rye or wheat dough is washed with water. It is the gluten that gives bread dough its elastic type quality. Flour from other major crop cereals barley, corn, sorghum, oat, millet and rice and also from the plant, soybean do not yield a gluten-like network under the conditions used for wheat and rye. 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 albumin, 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 “albumin” (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 albumin. You can also use this procedure to view pending patent applications concerning albumin. 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 ALBUMIN Overview This chapter provides bibliographic book references relating to albumin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on albumin 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 “albumin” (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 albumin: •
Insulin Resistance: The Metabolic Syndrome X Source: Totowa, NJ: Humana Press, Inc. 1999. 384 p. Contact: Available from Humana Press, Inc. Customer Service, 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. PRICE: $145.00 plus shipping and handling. ISBN: 0896035883. Summary: This book summarizes the current understanding of how insulin resistance and its compensating hyperinsulinemia play a role in the pathogenesis and clinical course of high blood pressure, cardiovascular disease, and polycystic ovary disease. Part one focuses on genetic and lifestyle factors that contribute to the differences in insulin action that exist in the population at large. Topics include the genetic determinants of insulin resistance, ethnic variation in insulin resistance and risk of type 2 diabetes, fetal effects on insulin resistance and glucose tolerance, obesity and insulin resistance, the
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role of body fat distribution in insulin resistance, physical activity and insulin resistance in humans, and insulin resistance in smokers and other long-term users of nicotine. Part two focuses on the pathophysiologic consequences of insulin resistance and the efforts made to compensate for this defect to prevent decompensation of glucose homeostasis. Topics include insulin resistance and inhibitors of insulin receptor tyrosine kinase, nuclear magnetic resonance studies on the mechanism of insulin resistance, skeletal muscle insulin resistance in humans, the role of the liver in insulin action and resistance, the pathophysiological consequences of adipose tissue insulin resistance, and insulin action and endothelial function. Part three considers the clinical syndromes excluding type 2 diabetes, that are related to insulin resistance. Topics include the implications of insulin resistance and dyslipidemia for coronary heart disease risk; insulin resistance and blood pressure; microalbuminuria and insulin resistance; plasminogen activation inhibitor, obesity, and insulin resistance; insulin resistance and cardiovascular disease; and insulin resistance effects on sex hormones and ovulation in the polycystic ovary syndrome. Numerous figures. 31 tables. Numerous references. •
Guidelines for the Nutritional Intervention of the Adult Dialysis Patient Source: Marina del Rey, CA: R and D Laboratories, Inc. 1990. 88 p. Contact: Available from R and D Laboratories, Inc. 4640 Admiralty Way, Suite 710, Marina del Rey, CA 90292. (800) 338-9066. PRICE: Contact directly for current price. Summary: This handbook is designed to assist the renal dietitian through the complex steps of evaluating the nutrition status of a dialysis patient. The guidelines are arranged by individual diagnoses or problems, and are based primarily on laboratory chemistries, presented as a quick reference. Expected patient outcome criteria are listed for each problem, along with a list of appropriate dietary interventions. A patient education documentation sheet suitable for use in the medical record is provided for each of the problems. Topics include hyperlipidemia, body weight changes, hyper-and hypocalcemia, hyperphosphatemia, elevated BUN, depressed serum albumin, hyperkalemia, fluid overload, and low hematocrit. 18 references.
Chapters on Albumin In order to find chapters that specifically relate to albumin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and albumin 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 “albumin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on albumin: •
Albumin Metabolism in the Nephrotic Syndrome: Implications for Patient Management Source: in Andreucci, V.E.; Fine, L.G., eds. International Yearbook of Nephrology 1991. Hingham, MA: Kluwer Academic Publishers. 1990. p. 121-138. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA02018-0358. (617) 871-6600. PRICE: $135.00. ISBN: 0792310020.
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Summary: The urinary loss of as little as 3.5 grams of protein a day (the amount of protein in half a hen's egg) may cause the entire spectrum of the nephrotic syndrome: severe hypoalbuminemia, hyperlipidemia, and edema formation. This chapter, from an international yearbook in nephrology, discusses albumin metabolism in the nephrotic syndrome, focusing on the implications for patient management. Topics covered include: homeostatic responses to the development of proteinuria; mobilization of the extravascular albumin pool; albumin catabolism; albumin catabolic rate in the nephrotic syndrome; regulation of albumin synthesis; albumin synthesis, dietary protein intake and albuminuria in the nephrotic syndrome; the effect of dietary protein on glomerular permselectivity; and tentative recommendations for patient management. 6 figures. 92 references. •
Microalbuminuria and Diabetic Pregnancy Source: in Mogensen, C.E. Kidney and Hypertension in Diabetes Mellitus. 3rd ed. Norwell, MA: Kluwer Academic Publishers. 1997. p. 415-422. Contact: Available from Kluwer Academic Publishers. 101 Philip Drive, Assinippi Park, Norwell, MA 02061. (617) 871-6600. Fax (617) 871-6528. PRICE: $130.00. ISBN: 0792343530. Summary: This chapter, from a medical text about kidney involvement and hypertension in diabetes, addresses the pattern of urinary albumin excretion rate in diabetic pregnancy as studied with a sensitive radioimmunoassay for albumin using 24 hour urine samples. The authors note that renal and vascular damage, including blood pressure elevation, are often involved in complications of pregnancies involving diabetes. Topics include patients, methods, and classifications; urinary albumin excretion during pregnancy; and urinary albumin excretion in the management of diabetic pregnancy. The chapter points out that new prognostic markers, with possible therapeutic implications, are clearly needed so that the frequency of harmful complications in diabetic pregnancy can be reduced to a level no higher than that in nondiabetic pregnancy. (AA-M).
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CHAPTER 7. PERIODICALS AND NEWS ON ALBUMIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover albumin.
News Services and Press Releases One of the simplest ways of tracking press releases on albumin 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 “albumin” (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 albumin. 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 “albumin” (or synonyms). The following was recently listed in this archive for albumin: •
Cardiovascular risk rises steadily as albuminuria worsens in patients with LVH Source: Reuters Medical News Date: December 11, 2003
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Microalbuminuria associated with higher mortality rates Source: Reuters Medical News Date: October 03, 2003
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Losartan reduces microalbuminuria in normotensive patients with diabetes Source: Reuters Industry Breifing Date: July 22, 2003
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Albumin volume expansion lowers mortality after bypass surgery Source: Reuters Medical News Date: July 02, 2003
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Renal insufficiency without albuminuria, retinopathy common in type 2 diabetics Source: Reuters Medical News Date: June 25, 2003
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Microalbuminuria frequently regresses in patients with type 1 diabetes Source: Reuters Medical News Date: June 04, 2003
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Serum albumin tied to outcome in women with HIV Source: Reuters Medical News Date: June 02, 2003
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Cobalt-binding capacity of albumin is a sensitive marker of coronary ischemia Source: Reuters Medical News Date: May 23, 2003
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Heart failure risk can be estimated in type 2 diabetics with microalbuminuria Source: Reuters Medical News Date: April 07, 2003
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FDA clears albumin test as a diagnostic aid in MI Source: Reuters Medical News Date: February 14, 2003
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Rapid drop in serum albumin in ICU indicates poor outcome Source: Reuters Medical News Date: February 03, 2003
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Serum albumin not linked to carotid atherosclerosis Source: Reuters Medical News Date: January 10, 2003
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Childhood BP predicts adult microalbuminuria in African Americans Source: Reuters Medical News Date: December 20, 2002
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Amlodipine and fosinopril curb hypertension, albuminuria in hypertensive diabetics Source: Reuters Industry Breifing Date: December 16, 2002
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Irbesartan reduces albumin excretion in normotensive diabetics Source: Reuters Industry Breifing Date: November 07, 2002
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Nocturnal blood pressure rises before microalbuminuria occurs in type 1 diabetes Source: Reuters Medical News Date: September 11, 2002
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High-normal albuminuria increases renal insufficiency risk in hypertensive men Source: Reuters Medical News Date: July 24, 2002
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Hypoalbuminemia, hypercreatinemia raise risk of diarrhea after renal transplant Source: Reuters Medical News Date: July 19, 2002
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Microalbuminuria, type 2 diabetes, CVD develop together over decades Source: Reuters Medical News Date: June 21, 2002
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Diet can improve microalbuminuria in type 2 diabetic patients Source: Reuters Medical News Date: April 02, 2002
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Pregnant women with microalbuminuria have high prevalence of preterm delivery Source: Reuters Medical News Date: November 19, 2001
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Microalbuminuria may not be a useful predictor of diabetic nephropathy Source: Reuters Medical News Date: October 11, 2001
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Urinary albumin helps delineate surgical stress in children Source: Reuters Medical News Date: September 17, 2001
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Value of microalbuminuria screening in diabetics questioned Source: Reuters Medical News Date: August 14, 2001
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ProMetic, Genzyme Transgenics to deliver recombinant albumin outside the US Source: Reuters Industry Breifing Date: July 25, 2001
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Even very low levels of microalbuminuria raise risk of cardiovascular events Source: Reuters Medical News Date: July 24, 2001
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Fresenius acquires further rights from Genzyme to transgenic albumin product Source: Reuters Industry Breifing Date: July 18, 2001
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Microalbuminuria linked to CVD mortality in older women Source: Reuters Medical News Date: June 25, 2001
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ACE inhibitor delays progression of diabetic microalbuminuria Source: Reuters Medical News Date: May 29, 2001
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High fish protein intake reduces risk of albuminuria in type 1 diabetics Source: Reuters Medical News Date: May 17, 2001
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ACE inhibitor therapy does not affect renal structure in diabetics with albuminuria Source: Reuters Industry Breifing Date: April 18, 2001
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ACE inhibitors slow progression to macroalbuminuria in type 1 diabetics Source: Reuters Industry Breifing Date: March 05, 2001
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Albumin-to-creatinine ratio can predict microalbuminuria risk Source: Reuters Medical News Date: January 01, 2001 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 “albumin” (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 “albumin” (or synonyms). If you know the name of a company that is relevant to albumin, 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 “albumin” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “albumin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on albumin: •
Nephropathy in NIDDM as Compared With IDDM Source: Diabetes News. 16(2): 5-8. 1995. Contact: Available from Excerpta Medica. P.O. Box 1126, 1000 BC Amsterdam, Netherlands. Summary: In this article, the author reports on nephropathy in people with noninsulindependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). The author notes that renal disease in both NIDDM and IDDM is frequently associated with poor metabolic control as well as with elevated blood pressure. To date, these two risk factors appear to be the only ones that are clearly linked to the development of renal disease, though several other modifying factors are known. Topics covered include population-based studies of individuals without known diabetes; renal function at the clinical diagnosis of diabetes; normal albumin excretion and the transition to microalbuminuria; overt diabetic retinopathy; end-stage renal failure; epidemiological studies; and screening. 2 figures. 2 tables. 12 references. (AA-M).
•
Interpreting Laboratory Values in the Renal Patient Source: Renal Nutrition Forum. 19(1): 1, 3-5. Winter 2000. Summary: This article, from a newsletter for renal (kidney) dietitians, focuses on interpreting laboratory values in the renal patient. The author reminds readers that every measurement in the clinical laboratory is made with an accuracy and precision determined in large part by the test methodology. The author explains the differences between accuracy (how well does the test measure what it is supposed to measure, i.e., validity) and precision (reproducibility, i.e., reliability). Renal failure itself also has a variety of effects on laboratory values. The most common of these result from loss of renal clearance. The renal handling of certain biochemical markers (e.g., serum protein prealbumin) must be considered in clinical interpretation of their values. Another effect from renal failure on laboratory values is the accumulation of normally cleared substances that interfere with an assay; common examples include therapeutic drug monitoring (for phenytoin and vancomycin, for example). Inability to take this reduction in clearance into consideration may lead to under dosing of the drugs involved. A further complication arises when drugs are bound to protein, especially albumin, in plasma (blood). The author concludes that both the clinician and the laboratory need to be aware of the importance of method selection when dealing with patients with renal failure. Two way communication is the key to the proper use of the laboratory results. One appendix reprints a sample monthly lab report, listing the lab test and acceptable level, a blank space for the patient's value to be entered, what to do if the level is too high or too low, the symptoms that the patient may experience, and why the level may have gotten high or low. The lab tests included are: BUN (blood urea
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nitrogen), albumin, potassium, phosphorus, calcium, and average fluid gain. 1 figure. 3 tables. 9 references. •
SSI Perspective: Overcoming Barriers to Employment Source: Renal Rehabilitation Report. 5(5): 4-5. September-October 1997. Contact: Available from Life Options Rehabilitation Program. Medical Education Institute, Inc, 414 D'Onofrid Drive., Suite 200, Madison, WI 53719. (608) 833-8033. Email:
[email protected]. Summary: This article, from a special issue on vocational rehabilitation and employment for dialysis patients, discusses overcoming barriers to employment. Many dialysis patients fear the potential loss of financial benefits they receive, either through Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI). The article provides a case study that illustrates how the SSI system works and how patients can best work within the SSI framework. The case study emphasizes the importance of working closely with the Social Security Administration (SSA) to learn about all the possibilities that are available for people with end-stage renal disease. The article then provides an interview that discusses common questions about SSI. The interview is with Wayne Nix, educational consultant for the National Kidney Foundation of Michigan and director of the OUTREACH: Renal Rehabilitation and Empowerment Program. Topics covered include SSI work incentives, Medicaid coverage, handling overpayment problems, the appeal process, where to get assistance with problems involving the SSI, vocational counseling, training and education issues, the role of part time work, and the indicators that are essential to health and rehabilitation (adequate dialysis, good hematocrit readings, acceptable serum albumin levels, properly controlled blood pressure, and a regular exercise program).
•
New Techniques for Improving Quality of Life on Dialysis Source: Clinical Strategies: The AKF Newsletter for Nephrology Professionals. 3(1): 4, 13-14. Summer 1996. Contact: Available from American Kidney Fund. 6110 Executive Boulevard, Suite 1010, Rockville, MD 20852. (800) 638-8299 or (301) 881-3052. Fax (301) 881-0898. Summary: This newsletter article reviews new techniques for improving quality of life on dialysis. The author emphasizes that, although the focus of this article is on techniques, some of the more recent advances in managing ESRD have come from better understanding the pathogenesis and clinical manifestations of uremia, the state of toxicity resulting from loss of kidney function. Topics include the use of erythropoietin; the importance of nutrition in the ESRD patient; prevention issues for the predialysis patient; dialysis amyloidosis; renal osteodystrophy; monitoring serum albumin concentration; peritoneal dialysis; advances in equipment design and function; vascular access complications; the importance of hemodialysis adequacy; and advances in other biomedical disciplines that impact dialysis therapy. 34 references.
Academic Periodicals covering Albumin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to albumin. In addition to these sources, you can search for articles covering albumin that have been published by any of the
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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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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for albumin. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with albumin. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to albumin: Albumin Microspheres Sonicated •
Systemic - U.S. Brands: Optison http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203714.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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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 “albumin” (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 132281 365 414 359 574 133993
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 “albumin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Albumin In the following section, we will discuss databases and references which relate to the Genome Project and albumin. 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 “albumin” (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 albumin: •
Albumin Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103600
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D Site of Albumin Promoter-binding Protein Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124097
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Lactalbumin, Alpha Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=149750 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
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome,
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Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
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
•
Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “albumin” (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 “albumin” (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 albumin 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 albumin. 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 albumin. 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 “albumin”:
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Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.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 albumin. 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: •
Microalbuminuria in Diabetic Kidney Disease Source: New York, NY: National Kidney Foundation. 1996. 5 p. Contact: Available from National Kidney Foundation of Southern California. 5777 West Century Boulevard, Suite 1450, Los Angeles, CA 90045-7404. (310) 641-8152. Fax (310) 641-5246. Website: www.kidneysocal.org. PRICE: Single copy free; bulk copies available. Summary: Kidney disease is one of the most serious complications of diabetes. After years of diabetes, the filtering units of the kidney (glomeruli) get scarred so that they cannot filter the blood efficiently. Eventually, the kidneys may fail completely so that the patient needs dialysis or a kidney transplant. This fact sheet offers readers with information about microalbuminuria in diabetic kidney disease. The risk factors for getting kidney disease for people with diabetes include having a family member with diabetic kidney disease (diabetic nephropathy), high blood glucose levels (hyperglycemia), high blood pressure (hypertension), and cigarette smoking. Microalbuminuria (microscopic protein in the urine) means that the kidney has some damage and is starting to spill some albumin (a kind of protein) in the urine. Microalbuminuria is measured by a specific urine test; routine urinalysis does not detect microalbuminuria. The microalbuminuria does not itself cause any symptoms. The fact sheet recommends that all people with diabetes (type 1 and type 2) should be tested for microalbuminuria. Readers are encouraged to keep their blood glucose levels in as tight control as possible, to lower the risk of all diabetes complications, including diabetic
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kidney disease. The fact sheet concludes with a brief description of the National Kidney Foundation (NKF) and its activities. 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 albumin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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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/
•
WebMDHealth: 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 albumin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with albumin. 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 albumin. 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.
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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “albumin” (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 “albumin”. 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 “albumin” (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 “albumin” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
24
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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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/
•
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/
•
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
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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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/
•
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
•
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
•
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/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on albumin: •
Basic Guidelines for Albumin Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm
•
Signs & Symptoms for Albumin Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm
•
Diagnostics and Tests for Albumin Bilirubin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Growth hormone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003706.htm
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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •
Nutrition for Albumin Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm
•
Background Topics for Albumin Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Burns Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000030.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Kidney disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000457.htm Necrosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002266.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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ALBUMIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [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] Acidemia: Increased acidity of blood. [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] Acrosome: Cap-like structure covering the nucleus and anterior part of the sperm head. [NIH]
Acrylamide: A colorless, odorless, highly water soluble vinyl monomer formed from the hydration of acrylonitrile. It is primarily used in research laboratories for electrophoresis, chromatography, and electron microscopy and in the sewage and wastewater treatment industries. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [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 leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow).
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[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 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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] 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] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris,
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glaucoma, migraine headaches, and anxiety. [NIH] Adrenoleukodystrophy: A chromosome X-linked disease. [NIH] 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] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [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]
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Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] 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] Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. [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] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [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] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] 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] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH]
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Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alpha-lactalbumin: A human milk protein which could be used as a nutritional supplement. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Aminocamptothecin: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of
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organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance
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of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Anhydrous: Deprived or destitute of water. [EU] 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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH]
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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] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anthraquinones: An anthracene ring which contains two ketone moieties in any position. Can be substituted in any position except on the ketone groups. [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] Antidote: A remedy for counteracting a poison. [EU] 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-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics
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(especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress 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] 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] Antiplasmin: A member of the serpin superfamily found in human plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. It is a glycoprotein, molecular weight approximately 70,000 that migrates in the alpha 2 region in immunoelectrophoresis. It is the principal plasmin inactivator in blood, rapidly forming a very stable complex with plasmin. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [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 associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU]
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Arterial Occlusive Diseases: Diseases in which arterial vessels are partially or completely obstructed or in which the blood flow through the vessels is impeded. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH]
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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] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] 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] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH]
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Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] 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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] 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] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]
Biliary Tract: The gallbladder and its ducts. [NIH]
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Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: 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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] 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] 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 non-
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synthetic (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] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood 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 Proteins: Proteins that are present in blood serum, including serum albumin, blood coagulation factors, and many other types of proteins. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [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] Blood-Testis Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the testis capillaries and seminiferous epithelium. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
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Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Body Weight Changes: A clinical manifestation consisting of alterations in an individual's weight from his or her norm. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bromcresol Green: An indicator and reagent. It has been used in serum albumin determinations and as a pH indicator. [NIH]
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Bromcresol Purple: An indicator and reatgent. It has been used for several purposes including the determination of serum albumin concentrations [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadaverine: A foul-smelling diamine formed by bacterial decarboxylation of lysine. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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]
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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] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] 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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [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] Carbaryl: A carbamate insecticide and parasiticide. It is a potent anticholinesterase agent belonging to the carbamate group of reversible cholinesterase inhibitors. It has a particularly low toxicity from dermal absorption and is used for control of head lice in some countries. [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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH]
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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] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [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] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [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] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell
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division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell 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] Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord.
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Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [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] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] 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
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unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] 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 Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and
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it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales, parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [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] 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] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active
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enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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
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the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conalbumin: A glycoprotein albumin from hen's egg white with strong iron-binding affinity. [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that
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provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or
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treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] 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] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cor pulmonale: Heart disease that results from resistance to the passage of blood through the lungs; it often leads to right heart failure. [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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [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]
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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corrosion: Irreversible destruction of skin tissue. [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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] 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] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] Coumarin: A fluorescent dye. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross Infection: Any infection which a patient contracts in a healthcare institution. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [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] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an
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increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] 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] Cyst: A sac or capsule filled with fluid. [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] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]
Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices.
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The process is usually preliminary to statistical analysis of the data. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [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] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Dental Amalgam: An alloy used in restorative dentistry that contains mercury, silver, tin, copper, and possibly zinc. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]
Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine
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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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] 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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diacetyl: Carrier of aroma of butter, vinegar, coffee, and other foods. [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] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions
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of the ventricles. [NIH] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [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]
Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [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] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU]
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Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]
Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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 Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [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
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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] 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] 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] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [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] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]
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Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
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] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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
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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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU]
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Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [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]
Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]
for
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] 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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] 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] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most
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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] Epirubicin: An anthracycline antibiotic which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, pancreatic cancer, gastric cancer, small-cell lung cancer and acute leukemia. It is equal in activity to doxorubicin but exhibits less acute toxicities and less cardiotoxicity. [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]
Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] 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] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
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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] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [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 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]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at
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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] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [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] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extravascular Lung Water: Water present within the lungs; its volume is roughly equal to, or a little less than, the intracellular blood volume of the lungs. Accumulations of extravascular lung water result in pulmonary edema. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [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]
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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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] 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] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [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] Filipin: A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important. [NIH]
Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fistulas: An abnormal passage from one hollow structure of the body to another, or from a
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hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [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] Flow Injection Analysis: The analysis of a chemical substance by inserting a sample into a carrier stream of reagent using a sample injection valve that propels the sample downstream where mixing occurs in a coiled tube, then passes into a flow-through detector and a recorder or other data handling device. [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 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] 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,
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and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Fossil Fuels: Any hydrocarbon deposit that may be used for fuel. Examples are petroleum, coal, and natural gas. [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] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frozen Sections: Thinly cut sections of frozen tissue specimens prepared with a cryostat or freezing microtome. [NIH] Fructosamine: An amino sugar formed when glucose non-enzymatically reacts with the Nterminal amino group of proteins. The fructose moiety is dervied from glucose by the "classical" Amadori rearrangement. [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] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] 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
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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] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Bypass: Surgical procedure in which the stomach is transected high on the body. The resulting proximal remnant is joined to a loop of the jejunum in an end-to-side anastomosis. This procedure is used frequently in the treatment of morbid obesity. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH]
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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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH]
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Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [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] Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with celiac disease. [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]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] 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] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after 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]
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Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] 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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] 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] 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]
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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] Grafting: The operation of transfer of tissue from one site to another. [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] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth Cones: Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis. [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] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gum Arabic: Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals. [NIH] Haematuria: Blood in the urine. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haemophilia: A haemorrhagic diathesis occurring in two main forms: 1. Haemophilia A (classic haemophilia, factor VIII deficiency), an X-linked disorder due to deficiency of coagulation factor VIII; 2. Haemophilia B (factor IX deficiency, Christmas disease), also X-
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linked, due to deficiency of coagulation factor IX. Both forms are determined by a mutant gene near the telomere of the long arm of the X chromosome (Xq), but a different loci, and are characterized by subcutaneous and intramuscular haemorrhages; bleeding from the mouth, gums, lips, and tongue; haematuria; and haemarthroses. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] 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] Hawaii: A group of islands in Polynesia, in the north central Pacific Ocean, comprising eight major and 114 minor islands, largely volcanic and coral. Its capital is Honolulu. It was first reached by Polynesians about 500 A.D. It was discovered and named the Sandwich Islands in 1778 by Captain Cook. The islands were united under the rule of King Kamehameha 1795-1819 and requested annexation to the United States in 1893 when a provisional government was set up. Hawaii was established as a territory in 1900 and admitted as a state in 1959. The name is from the Polynesian Owhyhii, place of the gods, with reference to the two volcanoes Mauna Kea and Mauna Loa, regarded as the abode of the gods. (From Webster's New Geographical Dictionary, 1988, p493 & Room, Brewer's Dictionary of Names, 1992, p2330 [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [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] Heart Transplantation: The transference of a heart from one human or animal to another.
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[NIH]
Heartbeat: One complete contraction of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematuria: Presence of blood in the urine. [NIH] Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [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] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] 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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to
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make enough of certain proteins needed to form blood clots. [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] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatic Veins: Veins which drain the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]
Hepatoma: A liver tumor. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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] Hetastarch: A derivative of starch used as a plasma substitute in the treatment of hemorrhage. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they
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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 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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [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 therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [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] Hospital Records: Compilations of data on hospital activities and programs; excludes patient medical records. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [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] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or
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disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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 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] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [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] 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] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [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] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [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] Hypertension, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [NIH] Hyperthermic perfusion: A procedure in which a warmed solution containing anticancer drugs is used to bathe, or is passed through the blood vessels of, the tissue or organ containing the tumor. [NIH] Hyperthyroxinemia: Excess of thyroxine in the blood. [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] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [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] Immersion: The placing of a body or a part thereof into a liquid. [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
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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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH]
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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] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] 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] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU]
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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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [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-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] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis,
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secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]
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] 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
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positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] 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 dipolar ions are at a maximum. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [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
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layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [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] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [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] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [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] 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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]
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Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [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] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [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] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH]
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Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] 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 A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [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] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liquid Ventilation: Artificial respiration using an oxygenated fluid. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH]
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Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] 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] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [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] 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
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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] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysinoalanine: N(6)-(2-Amino-2-carboxyethyl)-L-lysine. An unusual amino acid, not a dipeptide, which has been found in proteins of cooked foods. It is formed in food that is heated or treated with alkali. Has been implicated in nephrocytomegalia in rats. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely
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expressed in behaviour. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [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] Mean blood pressure: The average blood pressure, taking account of the rise and fall that occurs with each heartbeat. It is often estimated by multiplying the diastolic pressure by two, adding the systolic pressure, and then dividing this sum by three. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Meconium Aspiration: Syndrome caused by sucking of thick meconium into the lungs, usually by term or post-term infants (often small for gestational age) either in utero or with first breath. The resultant small airway obstruction may produce respiratory distress, tachypnea, cyanosis, pneumothorax, and/or pneumomediastinum. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] 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]
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Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanoma vaccine: A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with
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application chiefly in the areas of research and medicine. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [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] Microscopy, Atomic Force: A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample. [NIH] Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microtubule-Associated Proteins: High molecular weight proteins found in the
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microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] 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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [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 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] 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
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radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [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] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidose: Occurring in, or using multiple doses. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in
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chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [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] Myocardial Reperfusion: Generally, restoration of blood supply to heart 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. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH]
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Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] 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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [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] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] 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] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to
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6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] 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] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] 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
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nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [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] 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] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nidation: Implantation of the conceptus in the endometrium. [EU] 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] 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] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the
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next. [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] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] 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] Oligomenorrhea: Abnormally infrequent menstruation. [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] Oncotic: Pertaining to, caused by, or marked by swelling. [EU] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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] Ophthalmoscope: A lighted instrument used to examine the inside of the eye, including the retina and the optic nerve. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the
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retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] Organ Preservation: The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [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] Organic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] 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] 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] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of
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an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovarian Hyperstimulation Syndrome: Syndrome composed of a combination of ovarian enlargement and an acute fluid shift out of the intravascular space. The enlargement is caused by ovarian cyst formation and the fluid shift may result in ascites, hydrothorax, or generalized edema. The syndrome is most usually seen as a complication of ovulation induction, a treatment for infertility. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [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]
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Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paracentesis: A procedure in which fluid is withdrawn from a body cavity via a trocar and cannula, needle, or other hollow instrument. [NIH] Parathion: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide. [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] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are
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administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] 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] 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 Education: The teaching or training of patients concerning their own health needs. [NIH]
Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Initiation: The process whereby the formation of a peptide chain is started. This process requires (1) the 30s subunit, (2) the mRNA coding for the polypeptide to be made, (3) Met-tRNAi, (4) initiation factors, and (5) GTP. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood
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vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] 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] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove
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dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [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] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: 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] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photobiology: The branch of biology dealing with the effect of light on organisms. [NIH]
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Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physicochemical: Pertaining to physics and chemistry. [EU] 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] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma expander: Artificial plasma extender. [EU] 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] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating
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circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] 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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] 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 Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Pneumovirus: A genus of the familyParamyxoviridae (subfamily Pneumovirinae) where the human and bovine virions have neither hemagglutinin nor neuraminidase activity. Pneumonia virus of mice has hemagglutinin activity. Human respiratory syncytial virus is the type species. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [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]
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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [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] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [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]
Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polyethyleneimine: Strongly cationic polymer that binds to certain proteins; used as a marker in immunology, to precipitate and purify enzymes and lipids. Synonyms: aziridine polymer; Epamine; Epomine; ethylenimine polymer; Montrek; PEI; Polymin(e). [NIH] Polygeline: A 3.5 per cent colloidal solution containing urea- cross-linked polymerized peptides. It has a molecular weight of approximately 35,000 and is prepared from gelatin and electrolytes. The polymeric solution is used as a plasma expander. [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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They
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affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [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] 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] Polyurethanes: A group of thermoplastic or thermosetting polymers containing polyisocyanate. They are used as elastomers, as coatings, as fibers and as foams. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] 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
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symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [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] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Prions: Small proteinaceous infectious particles which resist inactivation by procedures that modify nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PrPSc proteins) and the cellular isoform PrPC (PrPC proteins). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include Creutzfeldt-Jakob syndrome and Gerstmann-Straussler syndrome. [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] 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]
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Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [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] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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] 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 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] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH]
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Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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 Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place
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when c-mos proteins are expressed at the wrong time. [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] Provirus: Virus that is integrated into the chromosome of a host cell and is transmitted in that form from one host cell generation to another without leading to the lysis of the host cells. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [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 Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [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] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine
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and ornithine. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Pyrogens: Substances capable of increasing body temperature; they may be of microbial origin, often polysaccharides and may contaminate distilled water. [NIH] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] 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] Radioactive iodine: A radioactive form of the chemical element iodine, often used for imaging tests or as a treatment for cancer. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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] 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]
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Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Raffinose: A trisaccharide occurring in Australian manna (from Eucalyptus spp, Myrtaceae) and in cottonseed meal. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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]
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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] 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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [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] Regional chemotherapy: Treatment with anticancer drugs that is directed to a specific area. [NIH]
Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [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]
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Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] 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] Renal Plasma Flow: The amount of plasma that perfuses the kidneys per unit time, approximately 10% greater than effective renal plasma flow (renal plasma flow, effective). It should be differentiated from the renal blood flow (RBF) which refers to the total volume of blood flowing through the renal vasculature, while the renal plasma flow refers to the rate of plasma flow (RPF). [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [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] 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] 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] Research Support: Financial support of research activities. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any
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of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [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] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH]
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Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [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] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses. [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]
Roentgenography: Production of an image of an object on film, or other kind of sensitized plate, usually by means of X-radiation or gamma radiation, the contrast between different areas of the image being the result of differential interaction of the radiation in the object. [NIH]
Root Caries: Dental caries involving the tooth root, cementum, or cervical area of the tooth. [NIH]
Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]
Saline: A solution of salt and water. [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]
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Salivary: The duct that convey saliva to the mouth. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [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] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called prions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] 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] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an
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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] Seminiferous tubule: Tube used to transport sperm made in the testes. [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] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] 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] 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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sertoli: One of the supporting cells of the seminiferous tubules, lying between clumps of germinal cells and having a number of spermatids partially buried in its cytoplasm. [NIH] Sertoli Cells: Supporting cells found in the seminiferous tubules of the testes in mammals. They surround and nourish developing sperm cells. They secrete androgen-binding protein and establish the blood-testis barrier. [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 Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to
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reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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]
Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [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] 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]
Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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]
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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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] Spectroscopic: The recognition of elements through their emission spectra. [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] Sperm Capacitation: The process by which a spermatozoon becomes capable of fertilizing an ovum after it reaches the ampullary portion of the uterine tube. [NIH] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [NIH] Spermatids: Male germ cells derived from spermatocytes and developing into spermatozoa. [NIH]
Spermatocytes: Male germ cells derived from spermatogonia and developing into spermatids. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermatozoon: The mature male germ cell. [NIH]
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Sphincters: Any annular muscle closing an orifice. [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] 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] Splenectomy: An operation to remove the spleen. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steatosis: Fatty degeneration. [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] Stellate: Star shaped. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [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] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat,
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chemical, or other means. [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] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [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] Stroma: The middle, thickest layer of tissue in the cornea. [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] Subcutaneous: Beneath the skin. [NIH] Sublimation: A defense mechanism through which unacceptable impulses and instinctive
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urges are diverted into personally and socially acceptable channels; e.g., aggression may be diverted through sports activities. [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] 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] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. [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] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which
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in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] 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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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 Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Systolic pressure: The highest pressure to which blood pressure rises with the contraction of the ventricles. [NIH] Tachypnea: Rapid breathing. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and
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atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Teniposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] 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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] 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] Thoracic: Having to do with the chest. [NIH] Thorium: Thorium. A radioactive element of the actinide series of metals. It has an atomic symbol Th, atomic number 90, and atomic weight 232.04. It is used as fuel in nuclear reactors
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to produce fissionable uranium isotopes. Because of its radioopacity, various thorium compounds are used to facilitate visualization in roentgenography. [NIH] Thorium Compounds: Inorganic compounds that contain thorium as an integral part of the molecule. [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] 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]
Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] 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]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]
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Tissue Adhesives: Substances used to cause adherence of tissue to tissue or tissue to nontissue surfaces, as for prostheses. [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 Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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] Toxicologic: Pertaining to toxicology. [EU] Toxicology: The science concerned with the detection, chemical composition, and
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pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] 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] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [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] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translation: The process whereby the genetic information present in the linear sequence of
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ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [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] Transport Vesicles: Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichosanthin: Plant-derived ribosome-inactivating protein purified from the Chinese medicinal herb tian-hua-fen which is obtained from the root tubers of Trichosanthes kirilowii. It has been used as an abortifacient and in the treatment of trophoblastic tumors. GLQ223 (Compound Q), a highly purified form of trichosanthin, has been proposed as antiviral treatment for AIDS. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [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]
Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [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] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other
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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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [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] Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [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] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH]
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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] Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] Urolithiasis: Stones in the urinary system. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage,
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secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [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] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU]
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Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Vinorelbine: 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 Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] Viremia: The presence of viruses in the blood. [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]
Dictionary 371
Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Vitellogenin: A serum and yolk protein which has been characterized as a calcium-binding glycolipophosphoprotein. It is induced by estrogen or juvenile hormone and is essential for yolk formation in various insect species. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [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] 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]
372
Albumin
Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
373
INDEX 3 3-dimensional, 67, 261, 346 A Abdomen, 261, 275, 296, 317, 321, 336, 338, 358, 359, 371 Abdominal, 28, 153, 164, 261, 262, 290, 317, 325, 336, 338 Abdominal Pain, 261, 338 Aberrant, 16, 52, 75, 107, 211, 261 Ablate, 171, 261, 294 Ablation, 171, 261 Abscess, 261, 301 Absolute risk, 9, 261 Acceptor, 30, 173, 200, 261, 321, 335, 363, 365 Acetylcholine, 146, 261, 281, 331, 332 Acidemia, 45, 261 Acidosis, 54, 261, 319 Acrosome, 143, 152, 261 Acrylamide, 128, 261 Acrylonitrile, 261 Actin, 55, 83, 261, 331 Actinin, 83, 261 Acute leukemia, 261, 297, 362, 370 Acute renal, 3, 211, 262 Acyl, 30, 79, 262 Adaptability, 262, 279 Adaptation, 262, 328, 341 Adduct, 29, 33, 66, 114, 134, 262 Adenine, 262, 347 Adenocarcinoma, 174, 262, 310, 346 Adenoma, 127, 262 Adenosine, 157, 262, 339 Adenosine Triphosphate, 157, 262, 339 Adenovirus, 64, 71, 76, 262 Adenylate Cyclase, 262, 281 Adipocytes, 66, 75, 262, 285, 320 Adipose Tissue, 37, 50, 224, 262 Adjuvant, 46, 152, 160, 198, 262 Adrenal Cortex, 262, 264, 287, 312, 344, 351 Adrenal Glands, 262, 266 Adrenal Medulla, 262, 296, 332 Adrenergic, 39, 262, 269, 297, 361 Adrenergic beta-Antagonists, 262, 269 Adrenoleukodystrophy, 81, 263 Adsorption, 24, 28, 45, 74, 77, 90, 91, 141, 176, 186, 263
Adsorptive, 263 Adverse Effect, 41, 195, 263, 339, 356 Aerobic, 263, 335 Aerobic Metabolism, 263, 335 Aerobic Respiration, 263, 335 Aerosol, 78, 263, 360 Afferent, 263, 320 Affinity, 22, 56, 105, 128, 140, 141, 147, 176, 180, 210, 214, 215, 218, 219, 263, 284, 321, 356 Affinity Chromatography, 215, 263 Agar, 263, 287, 340 Age of Onset, 263, 367 Age-Adjusted, 35, 263 Agonist, 30, 263, 282, 332 Airway, 18, 39, 78, 147, 149, 264, 324 Airway Obstruction, 264, 324 Alanine, 37, 53, 161, 264 Alanine Transaminase, 37, 264 Albuminuria, 6, 9, 12, 18, 138, 139, 140, 147, 225, 227, 228, 229, 264 Aldosterone, 39, 264 Algorithms, 18, 264, 273 Alimentary, 4, 264, 336, 337 Alkaline, 175, 180, 203, 261, 264, 265, 276, 339, 362 Alkaline Phosphatase, 180, 264 Alkaloid, 22, 264, 277, 332 Alkalosis, 54, 264, 362 Alleles, 38, 264, 321 Allergen, 264, 290, 355 Allogeneic, 183, 264 Allylamine, 264, 265 Alpha 1-Antitrypsin, 73, 264 Alpha Particles, 265, 348 Alpha-1, 131, 133, 265, 288, 339 Alpha-fetoprotein, 77, 83, 127, 211, 216, 265, 300 Alpha-lactalbumin, 77, 79, 89, 148, 151, 265 Alternative medicine, 230, 265 Aluminum, 94, 265 Alveoli, 265, 289, 369 Ameliorating, 189, 265 Amenorrhea, 265, 342 Amine, 33, 158, 180, 265, 311 Amino Acid Sequence, 46, 84, 168, 210, 215, 265, 266, 268, 298, 304, 344
374
Albumin
Amino Acid Substitution, 53, 265 Aminocamptothecin, 151, 162, 265 Amino-terminal, 87, 265 Ammonia, 86, 265, 306, 360, 367 Amnion, 266 Amniotic Fluid, 43, 266, 304, 324 Amplification, 82, 84, 85, 167, 212, 266 Amylase, 221, 266 Amyloid, 20, 53, 84, 266, 355 Amyloidosis, 52, 87, 232, 266 Anabolic, 62, 68, 266, 291 Anaerobic, 266, 329 Anaesthesia, 123, 266, 315 Anal, 142, 149, 150, 266, 299, 301, 322 Analgesic, 266, 291, 313, 320, 360 Analog, 107, 168, 192, 266, 301 Analogous, 25, 266, 342, 365 Anaphylaxis, 102, 160, 266 Anaplasia, 266, 346 Anastomosis, 117, 118, 266, 303 Anatomical, 266, 271, 280, 285, 314, 336, 354 Androgen-Binding Protein, 266, 355 Anemia, 154, 193, 245, 266, 274, 282, 302, 309 Anesthesia, 43, 264, 266, 267, 295 Anesthetics, 18, 267, 297 Aneuploidy, 22, 267 Angina, 72, 98, 128, 211, 262, 267 Angina Pectoris, 98, 128, 211, 262, 267 Angiography, 32, 267 Angiopathy, 20, 267 Angioplasty, 128, 267, 329 Angiotensin-Converting Enzyme Inhibitors, 104, 267, 269 Angiotensinogen, 28, 39, 267, 351 Anhydrous, 177, 267 Animal model, 16, 17, 25, 29, 35, 36, 37, 41, 44, 45, 211, 267 Anionic, 165, 267 Anions, 23, 76, 158, 264, 267, 318, 355 Ankle, 72, 267 Annealing, 267, 342 Anode, 267 Anorexia, 62, 153, 268, 367 Anovulation, 268, 342 Antecedent, 69, 268 Anterior Cerebral Artery, 268, 279 Anterior Cruciate Ligament, 34, 268 Anthracycline, 268, 289, 297, 313 Anthraquinones, 158, 268 Antibacterial, 268, 357, 369
Antibiotic, 268, 289, 292, 297, 313, 337, 342, 353, 357, 359 Antibodies, 69, 86, 114, 119, 138, 147, 163, 199, 207, 268, 308, 309, 312, 313, 314, 327, 340 Antibody, 22, 24, 74, 92, 96, 107, 157, 163, 173, 177, 189, 199, 202, 219, 263, 268, 283, 296, 297, 308, 311, 314, 315, 318, 324, 327, 348, 349, 355, 357, 371 Anticoagulant, 192, 201, 268, 346, 371 Anticonvulsant, 268, 277, 339 Antidote, 268, 276 Antifungal, 268, 300 Antigen-presenting cell, 88, 268, 289 Antihypertensive, 5, 13, 14, 89, 268 Antihypertensive Agents, 13, 268 Anti-inflammatory, 110, 269, 270, 290, 291, 305, 313, 360 Anti-Inflammatory Agents, 269, 270 Antimetabolite, 269, 289, 301, 326, 362 Antineoplastic, 162, 269, 292, 301, 325, 326, 336, 341, 362, 364, 368, 370 Antioxidant, 48, 91, 109, 150, 269, 270, 335 Antiplasmin, 30, 269 Antipyretic, 269, 291, 360 Antiviral, 77, 95, 269, 314, 316, 337, 366 Anuria, 269, 319 Anus, 266, 269, 283, 350 Aorta, 269, 277, 286, 325, 370 Apolipoproteins, 65, 67, 269, 321 Apoptosis, 37, 63, 77, 269 Aqueous fluid, 195, 269 Arachidonic Acid, 269, 345 Arginine, 53, 76, 161, 269, 311, 332, 334, 347, 366 Argon, 121, 269 Arterial, 6, 8, 13, 18, 33, 34, 65, 126, 131, 177, 187, 198, 219, 264, 269, 270, 275, 279, 281, 286, 313, 346, 361, 365 Arterial Occlusive Diseases, 219, 270 Arteries, 34, 187, 267, 269, 270, 274, 286, 318, 322, 325, 329, 347 Arteriolar, 72, 270, 275, 351 Arterioles, 58, 270, 274, 277, 326, 329 Arteriolosclerosis, 270 Arteriosclerosis, 67, 211, 270, 313 Arteriosus, 270, 347 Arteriovenous, 34, 270, 326 Artery, 30, 108, 267, 268, 269, 270, 286, 287, 290, 294, 295, 300, 318, 329, 347, 351, 361, 364 Articular, 270, 334
375
Artificial Organs, 116, 125, 270, 353 Ascites, 4, 75, 101, 116, 132, 270, 333, 335 Ascorbic Acid, 183, 185, 270, 312, 335 Aseptic, 161, 270, 334, 358 Aspartate, 37, 270 Aspiration, 270, 300 Aspirin, 192, 270 Assay, 5, 31, 36, 71, 85, 86, 97, 100, 107, 123, 127, 132, 158, 172, 174, 180, 187, 199, 200, 220, 231, 270, 314, 348, 353 Astigmatism, 270, 350 Astringents, 270, 325 Asymptomatic, 271, 336 Ataxia, 245, 271, 362 Atmospheric Pressure, 204, 271 Atrial, 102, 271, 286, 366, 371 Atrial Fibrillation, 102, 271, 371 Atrioventricular, 271, 286 Atrium, 271, 277, 286, 366, 370 Atrophy, 244, 245, 271, 297 Attenuated, 9, 271, 291 Atypical, 160, 271 Auditory, 107, 271 Autodigestion, 271, 336 Autoimmune disease, 17, 271 Autologous, 183, 271 Autopsy, 198, 271 Axons, 47, 271, 307, 317, 333, 334, 338 B Bacterial toxin, 56, 271 Bactericidal, 271, 298 Bacterium, 271, 285 Bacteriuria, 271, 368 Basal Ganglia, 271, 272, 275, 303 Basal Ganglia Diseases, 271, 272 Base, 73, 74, 176, 262, 264, 272, 289, 302, 304, 318, 319, 327, 338, 339, 341, 362, 367 Base Sequence, 272, 302, 304 Basement Membrane, 272, 299, 319 Basophil, 272, 311 Benign, 174, 211, 262, 270, 272, 300, 303, 308, 320, 330, 345, 349 Beta Rays, 272, 294 Beta-pleated, 266, 272 Beta-Thromboglobulin, 272, 316 Bewilderment, 272, 285 Bilateral, 272, 297, 342 Bile, 4, 59, 272, 273, 296, 303, 306, 310, 318, 321, 324, 359, 361 Bile Acids, 4, 272, 359, 361 Bile Acids and Salts, 272 Bile duct, 59, 272
Bile Pigments, 272, 318, 324 Biliary, 23, 42, 97, 272, 276, 310, 336 Biliary Atresia, 97, 272 Biliary Tract, 272, 276, 336 Binding Sites, 30, 82, 114, 123, 141, 192, 273 Bioassays, 29, 184, 273 Bioavailability, 23, 29, 219, 273 Biochemical reactions, 273, 362 Biological response modifier, 273, 316 Biological therapy, 273, 307 Biological Transport, 273, 291 Biomarkers, 29, 32, 40, 71, 90, 129, 273 Biomass, 212, 273 Biomechanics, 34, 273 Biopsy, 273, 337 Biosynthesis, 269, 273, 355, 368 Biotechnology, 73, 89, 121, 151, 167, 180, 230, 241, 243, 244, 245, 246, 273 Biotin, 44, 180, 183, 273 Biotransformation, 29, 273 Biphasic, 132, 274 Bladder, 33, 153, 177, 274, 281, 284, 302, 315, 331, 345, 368, 371 Blastocyst, 274, 284, 294 Blood Cell Count, 274, 309 Blood Coagulation, 162, 204, 274, 276, 353, 363 Blood Coagulation Factors, 204, 274 Blood Glucose, 6, 12, 13, 210, 214, 248, 274, 309, 313, 316 Blood Platelets, 220, 274, 324, 341, 355 Blood Proteins, 161, 274 Blood transfusion, 274, 309 Blood urea, 231, 274, 319 Blood Viscosity, 206, 274, 309 Blood Volume, 126, 142, 206, 274, 299 Blood-Brain Barrier, 44, 47, 53, 274, 330 Blood-Testis Barrier, 274, 355 Blot, 16, 69, 212, 274 Body Composition, 7, 275 Body Fluids, 264, 273, 275, 276, 293, 356, 366 Body Mass Index, 10, 72, 275, 335 Body Weight Changes, 224, 275 Bone Cements, 275, 343 Bone Marrow Cells, 275, 307, 324 Bone metastases, 275, 282 Boron, 275, 287 Bowel, 266, 275, 317, 320, 331, 338, 359 Brachial, 72, 275 Brachytherapy, 275, 317, 318, 348, 371
376
Albumin
Bradykinin, 275, 332, 340 Brain Hypoxia, 275, 362 Brain Infarction, 275 Brain Ischemia, 44, 275 Brain Stem, 275, 279, 331 Bromcresol Green, 4, 275 Bromcresol Purple, 4, 276 Bronchi, 276, 297, 365 Bronchial, 211, 276, 311 Bronchitis, 276, 281 Bronchoalveolar Lavage, 39, 276 Bronchoalveolar Lavage Fluid, 39, 276 Bronchoconstriction, 147, 149, 276 Bronchus, 276 Bullous, 129, 276 Bypass, 228, 276, 329 C Cachexia, 30, 88, 276 Cadaverine, 30, 276 Calcification, 270, 276 Calcium Channel Blockers, 269, 276 Calcium Chloride, 206, 276 Calcium Oxalate, 49, 124, 276 Calculi, 276 Callus, 276, 294 Camptothecin, 22, 120, 150, 277 Cancer vaccine, 277, 325 Cannula, 277, 336 Capillary, 19, 48, 53, 68, 71, 121, 126, 140, 141, 172, 275, 277, 305, 353, 370 Capillary Permeability, 19, 48, 71, 275, 277 Capsid, 213, 277 Capsules, 277, 300, 305 Carbamazepine, 120, 277 Carbaryl, 150, 277 Carbohydrate, 50, 277, 305, 306, 333, 343 Carbon Dioxide, 277, 289, 301, 303, 351, 367, 369 Carcinogen, 29, 33, 262, 277, 325, 368 Carcinogenesis, 63, 277, 280 Carcinogenic, 277, 315, 344, 359 Carcinoma, 16, 33, 84, 198, 277, 370 Cardiomyopathy, 52, 277 Cardiopulmonary, 101, 215, 277, 309 Cardiopulmonary Bypass, 101, 215, 277, 309 Cardiotoxicity, 277, 297 Cardiovascular disease, 6, 10, 15, 26, 28, 29, 48, 65, 72, 128, 223, 278, 321 Cardioversion, 102, 278 Carotene, 278, 352 Carrier Proteins, 163, 278, 340, 348
Castor Oil, 149, 177, 278 Catabolism, 79, 89, 225, 278 Catheter, 18, 131, 165, 190, 198, 278, 295 Catheterization, 267, 278, 329 Cathode, 267, 272, 278, 294 Cations, 103, 278, 318 Caudal, 278, 343 Causal, 50, 278, 309, 317 Cause of Death, 28, 187, 220, 278, 289 Caveolae, 48, 65, 278 Caveolins, 278 Celiac Disease, 114, 278, 305 Cell, 13, 16, 17, 19, 21, 23, 24, 31, 34, 35, 36, 37, 38, 45, 47, 48, 52, 59, 60, 63, 65, 66, 73, 76, 82, 85, 87, 88, 90, 94, 98, 104, 105, 109, 110, 116, 122, 146, 147, 154, 171, 173, 176, 178, 179, 183, 184, 185, 186, 191, 193, 197, 199, 208, 209, 211, 212, 216, 217, 244, 245, 261, 263, 265, 267, 268, 269, 270, 271, 273, 274, 276, 278, 279, 280, 281, 283, 285, 287, 288, 289, 290, 293, 294, 295, 297, 298, 299, 300, 301, 302, 303, 304, 307, 309, 310, 311, 312, 314, 315, 316, 317, 318, 319, 320, 323, 324, 327, 328, 329, 330, 331, 332, 333, 334, 335, 338, 339, 340, 341, 343, 345, 346, 347, 349, 351, 353, 354, 356, 357, 358, 359, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371 Cell Adhesion, 24, 278 Cell Aggregation, 90, 278, 334 Cell Cycle, 278, 298, 346, 362, 369 Cell Death, 48, 184, 269, 279, 298, 330, 362 Cell Differentiation, 147, 183, 212, 279, 356, 358 Cell Division, 244, 271, 279, 298, 307, 324, 327, 340, 345, 354 Cell membrane, 173, 209, 273, 276, 278, 279, 290, 298, 303, 318, 339, 343 Cell Membrane Structures, 278, 279 Cell proliferation, 104, 110, 212, 217, 270, 279, 316, 356 Cell Respiration, 263, 279, 335, 351 Cell Size, 279, 301 Cell Survival, 16, 185, 279, 307 Cellular adhesion, 107, 279 Central Nervous System, 87, 261, 264, 279, 280, 281, 303, 306, 308, 334, 355 Centrifugation, 24, 203, 279, 309, 326 Ceramide, 61, 279 Cerebellar, 183, 184, 271, 279, 350 Cerebellum, 275, 279, 350
377
Cerebral Cortex, 271, 279, 330, 348 Cerebral Infarction, 43, 275, 279 Cerebrospinal, 44, 279, 356 Cerebrospinal fluid, 44, 279, 356 Cerebrovascular, 187, 211, 220, 272, 276, 278, 280, 362 Cerebrum, 279, 280, 366 Cervical, 115, 128, 280, 353 Cervix, 280, 351 Character, 267, 280, 289, 306 Chemokines, 50, 280 Chemoprevention, 29, 280 Chemopreventive, 29, 280 Chemoprotective, 29, 280 Chemotaxis, 24, 280 Chemotherapy, 33, 90, 131, 145, 149, 193, 198, 280, 370 Chin, 26, 88, 280, 325 Chlamydia, 206, 280 Chloroform, 125, 280 Chlorophyll, 280, 302 Chloroplasts, 212, 280 Cholecystokinin, 53, 280 Cholera, 65, 212, 280, 281, 370 Cholera Toxin, 212, 281 Cholesterol Esters, 193, 281, 321 Cholinergic, 281, 332 Cholinesterase Inhibitors, 277, 281 Chondrocytes, 183, 185, 281, 300 Chromatin, 38, 78, 79, 269, 281, 323, 357 Chromosomal, 18, 22, 38, 40, 41, 66, 74, 266, 267, 281, 304, 311, 362 Chromosome, 18, 82, 109, 217, 263, 267, 281, 285, 308, 321, 328, 347, 354, 362, 366, 367 Chronic Disease, 276, 281, 283 Chronic Obstructive Pulmonary Disease, 211, 281 Chronic renal, 21, 62, 81, 193, 210, 211, 281, 303, 342, 367 Chylomicrons, 281, 321 Ciliary, 269, 270, 281 Ciliary processes, 269, 281 Circadian, 101, 281 Circadian Rhythm, 101, 281 Circulatory system, 219, 281 Cirrhosis, 4, 50, 116, 126, 133, 282 CIS, 118, 141, 282, 352 C-kit receptor, 282, 358 Clamp, 51, 282 Claviceps, 282, 353 Clear cell carcinoma, 282, 290
Clinical Medicine, 129, 148, 204, 282, 343 Clinical trial, 15, 44, 51, 56, 58, 64, 68, 212, 241, 282, 286, 288, 292, 346, 349 Clodronate, 207, 282 Clomiphene, 105, 282 Cloning, 75, 167, 174, 273, 282 Coagulation, 117, 149, 195, 274, 282, 307, 310, 340, 371 Cobalt, 129, 172, 187, 220, 228, 282 Codon, 212, 282, 304 Coenzyme, 270, 282 Cofactor, 162, 283, 332, 346, 363 Collagen, 30, 69, 104, 170, 179, 214, 272, 283, 299, 300, 312, 324, 341, 344 Collagen disease, 283, 312 Collapse, 45, 266, 283, 341 Colloidal, 83, 97, 264, 283, 294, 298, 338, 342, 355, 360 Colon, 81, 123, 198, 244, 283, 319 Colorectal, 198, 283 Colorectal Cancer, 198, 283 Combinatorial, 92, 283 Communis, 278, 283 Complement, 283, 284, 304, 323, 340, 355 Complementary and alternative medicine, 145, 155, 284 Complementary medicine, 145, 284 Complementation, 38, 284 Complete remission, 284, 351 Compliance, 21, 30, 126, 284 Computational Biology, 241, 243, 284 Computed tomography, 108, 284 Computer Simulation, 34, 284 Computerized axial tomography, 284 Computerized tomography, 284 Conalbumin, 78, 284 Concentric, 270, 284, 332 Conception, 284, 285, 300, 358 Concomitant, 7, 10, 284 Conduction, 27, 69, 284 Cones, 284, 352 Confounding, 54, 71, 285 Confusion, 120, 285, 292, 367, 368 Congestion, 285, 297 Congestive heart failure, 44, 72, 285, 321 Conjugated, 30, 106, 114, 126, 163, 166, 272, 285, 288, 329, 353 Conjugation, 189, 274, 285 Conjunctiva, 285, 315 Connective Tissue, 42, 270, 275, 283, 285, 290, 300, 303, 322, 325, 338, 359, 362 Connective Tissue Cells, 285
378
Albumin
Consciousness, 266, 285, 289, 292, 310, 352 Constipation, 285, 338 Constriction, 187, 220, 285, 318, 369 Constriction, Pathologic, 285, 369 Consultation, 56, 285 Contamination, 168, 185, 191, 285, 310 Continuum, 118, 187, 285 Contraception, 36, 285 Contractility, 267, 285, 293 Contraindications, ii, 285 Contrast medium, 267, 286 Control group, 63, 286, 344, 349 Conus, 286, 347 Convulsions, 268, 286, 293, 344 Coordination, 66, 279, 286 Cor, 211, 286 Cor pulmonale, 211, 286 Cornea, 269, 270, 286, 359 Coronary, 11, 26, 32, 72, 98, 108, 116, 135, 224, 228, 267, 278, 286, 287, 329 Coronary Arteriosclerosis, 286, 329 Coronary Artery Bypass, 135, 286 Coronary Circulation, 267, 286 Coronary heart disease, 11, 26, 72, 224, 278, 286 Coronary Thrombosis, 287, 329 Corrosion, 132, 287 Cortex, 287, 311, 350 Cortical, 30, 287, 298, 354, 362 Corticosteroids, 42, 287, 305 Cortisol, 264, 287 Cortisone, 287, 290 Cost Savings, 188, 287 Coumarin, 192, 287 Creatinine clearance, 9, 140, 287 Critical Care, 51, 91, 92, 98, 110, 114, 133, 135, 136, 287 Cross Infection, 96, 287 Crossing-over, 287, 350 Cryostat, 287, 302 Culture Media, 183, 184, 185, 191, 263, 287 Cultured cells, 65, 287 Curative, 287, 332, 353, 362 Curcumin, 132, 287 Cutaneous, 287, 340 Cyanogen Bromide, 93, 287 Cyanosis, 287, 324 Cyclic, 31, 60, 262, 288, 307, 332, 345 Cyclodextrins, 36, 288 Cyclosporine, 6, 288 Cyst, 288, 335
Cysteine, 94, 111, 117, 142, 280, 288, 292, 360 Cystine, 221, 288, 292 Cytochrome, 17, 142, 150, 288 Cytokine, 19, 30, 61, 68, 177, 207, 288, 316 Cytoplasm, 269, 279, 281, 288, 296, 323, 331, 332, 353, 355, 361 Cytoskeletal Proteins, 69, 288 Cytoskeleton, 34, 288, 327 Cytostatic, 162, 163, 288 Cytotoxic, 22, 47, 163, 288, 314, 349, 356 Cytotoxicity, 23, 264, 288 Cytotoxins, 213, 288 D Data Collection, 56, 288 Daunorubicin, 162, 289, 292 Deamination, 289, 367 Death Certificates, 73, 289 Decarboxylation, 276, 289, 311, 347 Decompensation, 224, 264, 289 Deferoxamine, 48, 289 Degenerative, 286, 289, 310, 334, 352 Dehydration, 208, 209, 280, 289 Dehydroepiandrosterone, 101, 289 Deletion, 42, 52, 73, 74, 92, 168, 196, 269, 289, 304 Delivery of Health Care, 289, 308 Dementia, 289, 331 Denaturation, 195, 203, 289, 342 Dendrites, 289, 307, 331 Dendritic, 207, 289, 324 Dendritic cell, 207, 289 Dental Amalgam, 26, 41, 289 Dentition, 41, 289 Deoxyguanosine, 29, 289 Deoxyribonucleic, 289, 353 Deoxyribonucleic acid, 289, 353 Deoxyuridine, 198, 289, 363 Depolarization, 290, 356 Deprivation, 187, 290 Dermis, 102, 147, 183, 290, 360, 365 DES, 215, 290 Desensitization, 290, 314 Detoxification, 182, 290, 306 Deuterium, 66, 100, 290, 312 Dexamethasone, 183, 290 Diabetes Mellitus, 5, 6, 7, 8, 9, 10, 11, 13, 14, 19, 56, 133, 205, 211, 214, 225, 231, 290, 305, 309 Diabetic Retinopathy, 231, 290, 340 Diacetyl, 180, 290 Diagnostic procedure, 159, 230, 290
379
Dialysate, 290 Dialyzer, 103, 290, 309 Diaphragm, 19, 290, 341 Diarrhea, 160, 229, 290 Diastole, 290 Diastolic, 10, 12, 28, 84, 290, 313, 324 Diastolic blood pressure, 10, 12, 28, 290 Diastolic pressure, 290, 313, 324 Diathesis, 291, 307 Diclofenac, 96, 291 Diclofenac Sodium, 291 Dietary Fats, 291, 321 Dietitian, 224, 291 Diffusion, 53, 57, 165, 170, 190, 218, 273, 277, 291, 307, 315, 367 Digestion, 264, 272, 275, 291, 317, 321, 337, 359, 368 Digestive tract, 291, 356, 358 Dihydrotestosterone, 291, 350 Dihydroxy, 264, 291, 298, 353 Dilated cardiomyopathy, 126, 291 Dilution, 91, 186, 199, 291, 297, 340 Diphtheria, 171, 291 Diphtheria Toxin, 171, 291 Diploid, 267, 284, 291, 328, 340, 366 Discrete, 18, 59, 62, 291, 305, 322, 362 Discrimination, 142, 291 Disease Progression, 291, 370 Disinfectant, 291, 298 Disorientation, 285, 292 Dissection, 135, 292 Dissociation, 23, 63, 85, 263, 292 Dissociative Disorders, 292 Distal, 25, 286, 292, 294, 338, 347 Disulphides, 292 Dithiothreitol, 221, 292 Diuresis, 51, 292 Diuretic, 51, 276, 292, 303, 324, 357 Diuretics, Thiazide, 269, 292 Docetaxel, 162, 292 Dorsal, 292, 343 Double-blind, 9, 292 Doxorubicin, 90, 162, 292, 297 Drug Delivery Systems, 177, 207, 292 Drug Interactions, 17, 192, 236, 292 Drug Monitoring, 131, 219, 231, 292 Drug Tolerance, 292, 364 Duct, 211, 277, 278, 293, 298, 323, 354, 360 Duodenum, 272, 293, 318, 337, 359 Dyes, 215, 266, 293, 301 Dyslipidemia, 14, 28, 224, 293 Dysplasia, 245, 293
Dyspnea, 289, 293 Dystrophy, 244, 293 E Echocardiography, 44, 135, 179, 185, 293 Eclampsia, 272, 293, 344 Ectopic, 211, 293 Edema, 47, 51, 71, 175, 225, 289, 290, 293, 303, 329, 330, 333, 335, 344, 367 Effector, 47, 178, 261, 283, 293 Effector cell, 47, 178, 293 Ejection fraction, 44, 293 Elastic, 222, 293, 306, 357, 360, 364 Elasticity, 270, 286, 293 Elastin, 170, 283, 293, 299 Elastomers, 293, 343 Elective, 128, 293 Electrocardiography, 72, 118, 293 Electrocoagulation, 282, 294 Electrode, 202, 267, 278, 294 Electrolysis, 267, 278, 294 Electrolyte, 43, 264, 294, 309, 319, 343, 356, 367 Electrons, 173, 269, 272, 278, 294, 317, 323, 335, 348, 349 Electrophoresis, 121, 140, 141, 146, 261, 294, 314 Elementary Particles, 294, 323, 331, 346 Emboli, 33, 98, 294, 371 Embolism, 294, 347, 371 Embolization, 98, 294, 371 Embryo, 44, 113, 171, 266, 274, 279, 294, 315, 342 Embryo Transfer, 113, 294 Embryogenesis, 63, 294, 358 Embryology, 42, 294 Emollient, 294, 327 Emphysema, 264, 281, 294 Empirical, 175, 294 Emulsion, 188, 208, 294, 301 Enalapril, 9, 138, 295 Encapsulated, 96, 158, 207, 208, 295, 321 Encephalopathy, 185, 295 Endarterectomy, 267, 295 Endemic, 280, 295, 358 Endocytosis, 65, 91, 278, 295 Endogenous, 11, 79, 86, 210, 220, 274, 295, 306, 335, 346, 365, 366 Endothelial cell, 31, 48, 55, 65, 82, 91, 109, 113, 146, 175, 207, 274, 295, 300, 316, 363 Endothelium, 31, 48, 53, 88, 91, 295, 332 Endothelium, Lymphatic, 295 Endothelium, Vascular, 295
380
Albumin
Endothelium-derived, 295, 332 Endotoxic, 295, 321 Endotoxin, 61, 90, 100, 147, 207, 295, 367 End-stage renal, 4, 5, 13, 14, 28, 55, 62, 135, 231, 232, 281, 295, 342 Energy balance, 295, 320 Enhancer, 17, 76, 79, 83, 87, 88, 171, 295, 352 Enterohepatic, 295, 296, 360 Enterohepatic Circulation, 296, 360 Enteropeptidase, 296, 366 Environmental Exposure, 296, 333 Environmental Health, 134, 240, 242, 296 Environmental Pollutants, 40, 296 Enzymatic, 16, 103, 126, 141, 157, 174, 210, 276, 278, 283, 296, 311, 342, 352 Enzyme Inhibitors, 296, 340 Enzyme-Linked Immunosorbent Assay, 138, 296 Eosinophil, 147, 296, 307 Eosinophilic, 296 Epidemic, 40, 166, 296, 358 Epidemiological, 71, 231, 296 Epidermal, 196, 212, 213, 296, 318, 324 Epidermal Growth Factor, 212, 213, 296 Epidermis, 290, 296, 318 Epidermoid carcinoma, 296, 358 Epigastric, 296, 336 Epinephrine, 262, 296, 331, 332, 367 Epirubicin, 162, 297 Epithelial, 19, 24, 39, 75, 174, 197, 212, 262, 273, 281, 296, 297, 318, 319, 345 Epithelial Cells, 19, 75, 281, 296, 297, 318, 319, 345 Epithelium, 42, 174, 272, 274, 295, 297, 346 Epitope, 199, 297 Ergot, 297, 353 Erythema, 99, 297, 368 Erythema Nodosum, 99, 297 Erythrocyte Indices, 274, 297 Erythrocyte Volume, 274, 297 Erythrocytes, 88, 133, 194, 266, 274, 275, 297, 309, 350, 355 Erythropoietin, 168, 193, 211, 217, 232, 297 Escalation, 43, 297 Esophagus, 291, 297, 337, 339, 350, 359, 370 Essential Tremor, 244, 297 Estrogen, 74, 76, 282, 297, 371 Estrogen receptor, 74, 282, 297 Ethanol, 36, 54, 89, 185, 193, 298, 300 Ethanolamine, 184, 298
Ether, 142, 298 Ethylene Glycol, 24, 120, 150, 163, 298 Etoposide, 162, 298 Eukaryotic Cells, 216, 288, 298, 334, 367 Excipient, 216, 298, 307 Excitation, 298, 301, 331 Excitatory, 298, 306 Excitotoxicity, 184, 298 Excrete, 269, 298, 319, 351 Exocrine, 280, 298, 336 Exocytosis, 298, 311, 361 Exogenous, 172, 187, 220, 263, 273, 295, 298, 304, 306, 346, 366, 367 Exon, 59, 79, 82, 298 Expander, 161, 176, 298 Expiration, 298, 351 Expiratory, 18, 298 Extender, 298, 340 External-beam radiation, 298, 318, 348, 371 Extracellular Matrix, 19, 58, 81, 216, 285, 299, 300, 324 Extracellular Matrix Proteins, 81, 299, 324 Extracellular Space, 299, 326 Extracorporeal, 18, 126, 201, 299, 309 Extraction, 105, 165, 168, 198, 203, 216, 217, 299 Extrapyramidal, 45, 299 Extravascular, 51, 178, 225, 299 Extravascular Lung Water, 51, 299 Extremity, 72, 299 Exudate, 299, 307 Eye Infections, 262, 299 F Family Planning, 241, 299 Fatigue, 299, 308 Fatty Liver, 36, 50, 299 Febrile, 133, 299 Fecal Incontinence, 120, 299, 315 Feces, 285, 299, 300, 359 Femoral, 34, 277, 300 Femoral Artery, 277, 300 Femur, 268, 300, 363 Fermentation, 210, 213, 300 Fetoprotein, 79, 216, 300 Fetus, 265, 297, 300, 324, 344, 368 Fibril, 53, 300 Fibrin, 205, 219, 269, 274, 300, 338, 341, 363, 364 Fibrinogen, 26, 27, 30, 51, 72, 74, 77, 78, 80, 84, 90, 98, 106, 117, 206, 219, 300, 340, 363
381
Fibroblast Growth Factor, 212, 300 Fibroblasts, 285, 300, 316 Fibroid, 211, 300, 320 Fibronectin, 24, 27, 30, 105, 206, 300 Fibrosis, 18, 37, 50, 211, 245, 264, 300, 354 Filipin, 152, 300 Filler, 161, 300 Filtration, 50, 69, 109, 125, 148, 169, 186, 191, 300, 319 Fine-needle aspiration, 300, 330 Fistulas, 97, 300 Fixation, 102, 301, 355 Flatus, 299, 301, 303 Flow Cytometry, 17, 301 Flow Injection Analysis, 99, 301 Fluorescence, 32, 45, 47, 78, 90, 106, 125, 127, 132, 149, 152, 178, 301, 326 Fluorescent Dyes, 301 Fluorouracil, 198, 301 Folate, 68, 290, 301, 302 Fold, 18, 35, 40, 212, 213, 301, 325 Folic Acid, 111, 152, 301 Follicles, 302, 315 Follow-Up Studies, 11, 302 Forearm, 274, 302 Fosinopril, 228, 302 Fossil Fuels, 71, 302 Fovea, 301, 302 Fractionation, 56, 80, 126, 302 Frameshift, 74, 302 Free Radicals, 109, 172, 173, 269, 292, 302, 329 Freeze Drying, 204, 209, 302 Freeze-dried, 168, 302 Friction, 302, 322 Frontal Lobe, 268, 279, 302 Frozen Sections, 46, 302 Fructosamine, 107, 140, 200, 205, 302 Fructose, 302, 306, 317 Fundus, 56, 302, 333 Fungus, 297, 302, 353 Furosemide, 51, 303 G Gadolinium, 32, 136, 303 Gallbladder, 261, 272, 280, 302, 303 Gamma Rays, 172, 303, 348, 349 Ganglia, 261, 272, 303, 330, 360 Ganglion, 303, 333, 334 Ganglionic Blockers, 269, 303 Ganglioside, 213, 303 Gap Junctions, 303, 361 Gas exchange, 18, 303, 351, 369
Gastric, 51, 68, 84, 271, 296, 297, 303, 311, 337 Gastric Bypass, 51, 303 Gastric Juices, 303, 337 Gastrin, 303, 311 Gastrointestinal tract, 281, 298, 300, 303, 320, 355, 358, 366 Gels, 18, 196, 205, 304 Gene Deletion, 52, 304 Gene Expression, 18, 38, 46, 54, 83, 85, 88, 178, 184, 245, 304 Gene Targeting, 45, 89, 304 Gene Therapy, 45, 64, 165, 166, 262, 304 Genetic Code, 304, 332 Genetic Engineering, 196, 273, 282, 304, 350 Genetic Markers, 40, 304 Genetic Techniques, 40, 304 Genetic testing, 304, 342 Genetics, 13, 39, 52, 82, 167, 285, 304 Genotype, 19, 28, 64, 134, 304, 339 Germ Cells, 304, 324, 333, 335, 357 Gestation, 214, 304 Gestational, 43, 56, 123, 154, 304, 324 Gestational Age, 43, 123, 304, 324 Ginseng, 155, 305 Gland, 78, 262, 287, 305, 322, 336, 340, 345, 354, 359, 360, 363 Gliadin, 222, 305 Glioma, 104, 305 Glomerular Filtration Rate, 12, 14, 29, 62, 147, 305, 319, 324 Glomeruli, 69, 129, 150, 248, 305 Glomerulosclerosis, 58, 129, 305 Glomerulus, 305, 330 Glucans, 288, 305 Glucocorticoid, 290, 305, 312 Glucose Intolerance, 15, 56, 290, 305 Glucose tolerance, 56, 223, 305 Glucose Tolerance Test, 56, 305 Glucuronic Acid, 305, 306, 310, 368 Glucuronides, 23, 79, 305, 306 Glutamate, 70, 184, 264, 298, 306 Glutamic Acid, 88, 301, 306, 309, 331, 344 Glutamine, 64, 184, 306 Glutathione Peroxidase, 306, 355 Gluten, 221, 278, 305, 306 Glycine, 161, 180, 272, 306, 331, 355 Glycogen, 66, 280, 306, 339 Glycols, 306, 312 Glycolysis, 70, 306 Glycosaminoglycans, 299, 306
382
Albumin
Glycoside, 306, 354 Glycosidic, 306, 331, 339 Glycosylation, 86, 140, 168, 306 Gonadal, 306, 359 Governing Board, 306, 343 Gp120, 306, 337 Grade, 58, 307, 346 Graft, 34, 135, 307, 329 Grafting, 286, 307, 314 Gram-negative, 90, 280, 295, 307, 329, 370 Granule, 30, 84, 183, 184, 307, 353 Granulocyte, 39, 217, 307 Granulocyte-Macrophage ColonyStimulating Factor, 39, 307 Granulosa Cells, 112, 307, 315 Grasses, 282, 302, 307 Gravis, 307, 330, 348 Growth Cones, 47, 307 Growth factors, 43, 46, 59, 163, 184, 185, 212, 213, 216, 307 Guanine, 289, 307, 347 Guanylate Cyclase, 307, 332 Gum Arabic, 209, 307 H Haematuria, 307, 308 Haemodialysis, 215, 307 Haemophilia, 168, 307 Hair follicles, 290, 308, 371 Half-Life, 172, 196, 218, 308 Haploid, 308, 340 Haplotypes, 28, 308 Haptens, 263, 308, 348 Hawaii, 143, 253, 308 Headache, 308, 315 Health Care Costs, 62, 308 Health Expenditures, 308 Health Promotion, 15, 308 Health Status, 21, 308 Heart attack, 278, 308 Heart failure, 211, 228, 267, 286, 308, 333 Heart Transplantation, 126, 308 Heartbeat, 309, 324 Hematocrit, 21, 224, 232, 274, 297, 309 Hematopoietic Stem Cells, 16, 309 Hematuria, 6, 309 Hemin, 77, 99, 309 Hemodiafiltration, 169, 309, 367 Hemodialysis, 21, 54, 62, 68, 98, 103, 116, 118, 120, 143, 151, 169, 232, 290, 309, 319, 367 Hemodilution, 152, 206, 309 Hemodynamics, 25, 34, 51, 309
Hemofiltration, 169, 309, 367 Hemoglobin A, 9, 71, 99, 120, 309 Hemoglobin C, 132, 297, 309 Hemoglobinopathies, 304, 309 Hemoglobinuria, 244, 309 Hemolysis, 91, 309 Hemophilia, 162, 245, 309 Hemorrhage, 44, 102, 164, 211, 290, 294, 308, 310, 329, 359 Hemostasis, 65, 310, 355 Heparin, 107, 201, 310, 341 Hepatic Encephalopathy, 131, 310 Hepatic Veins, 198, 310 Hepatitis, 17, 29, 35, 37, 81, 134, 181, 213, 310, 370 Hepatitis A, 37, 310 Hepatobiliary, 23, 310 Hepatoblastoma, 16, 310 Hepatocellular, 16, 29, 35, 63, 127, 310 Hepatocellular carcinoma, 16, 29, 35, 127, 310 Hepatocyte, 17, 36, 37, 42, 59, 61, 63, 64, 85, 87, 108, 198, 216, 310 Hepatology, 4, 126, 131, 310 Hepatoma, 38, 73, 85, 86, 88, 310 Hepatorenal Syndrome, 131, 310 Hepatovirus, 310 Hereditary, 87, 127, 264, 309, 310, 338, 340, 352 Heredity, 304, 310 Herpes, 76, 310 Herpes Zoster, 310 Hetastarch, 102, 310 Heterogeneity, 80, 111, 263, 310 Hippocampus, 311, 331 Histamine, 102, 149, 311 Histamine Release, 102, 311 Histidine, 114, 311 Histology, 30, 42, 47, 70, 71, 311, 331 Histones, 281, 311 Homeostasis, 38, 139, 224, 311 Homodimer, 46, 311, 365 Homogeneous, 39, 195, 270, 285, 311 Homologous, 38, 79, 158, 264, 287, 288, 304, 309, 311, 328, 354, 355, 361 Hormonal, 52, 271, 311, 371 Hormone, 30, 61, 83, 110, 124, 185, 257, 264, 266, 273, 281, 287, 290, 296, 297, 303, 311, 315, 316, 317, 320, 325, 344, 352, 356, 362, 363, 365, 371 Hormone therapy, 30, 311 Horseradish Peroxidase, 24, 180, 296, 311
383
Hospital Records, 73, 311 Human Genome Project, 179, 246, 311 Humoral, 311, 363 Hyaluronidase, 57, 311 Hybrid, 64, 88, 117, 218, 312, 353 Hybridomas, 312, 316 Hydration, 57, 261, 312 Hydrocortisone, 185, 312 Hydrogel, 202, 312 Hydrogen Bonding, 23, 67, 312 Hydrogen Peroxide, 306, 312, 321 Hydrolysis, 22, 174, 210, 274, 312, 321, 331, 339, 343, 346, 366 Hydrophilic, 312 Hydrophobic, 79, 80, 106, 208, 210, 215, 312, 321 Hydroxides, 312 Hydroxyl Radical, 150, 312 Hydroxylysine, 283, 312 Hydroxyproline, 283, 312 Hyperbilirubinemia, 23, 215, 312, 318 Hypercalcemia, 282, 312 Hypercholesterolemia, 34, 293, 312 Hyperglycemia, 11, 13, 19, 58, 70, 139, 248, 312 Hyperlipidemia, 85, 224, 225, 293, 312 Hyperlipoproteinemia, 312, 313 Hyperopia, 313, 350 Hypersensitivity, 160, 177, 264, 266, 290, 296, 313, 352, 355 Hypertension, Pulmonary, 211, 313 Hyperthermic perfusion, 121, 313 Hyperthyroxinemia, 87, 105, 130, 313 Hypertriglyceridemia, 15, 293, 313 Hypertrophy, 211, 286, 313, 366 Hypoglycemic, 56, 313 Hypotensive, 121, 313 Hypothermia, 309, 313 I Ibuprofen, 96, 102, 313, 360 Idarubicin, 162, 313 Idiopathic, 123, 126, 313 Imaging procedures, 313, 365 Imidazole, 200, 273, 311, 313 Immersion, 209, 313 Immune response, 36, 47, 108, 158, 178, 197, 262, 268, 271, 287, 308, 313, 314, 323, 355, 360, 368, 370, 371 Immune Sera, 313 Immune system, 13, 177, 197, 268, 273, 293, 313, 314, 323, 338, 368, 371
Immunity, 46, 83, 124, 201, 264, 288, 313, 314, 365 Immunization, 108, 213, 313, 344, 355 Immunoassay, 8, 69, 90, 100, 107, 121, 127, 173, 199, 208, 296, 314 Immunodeficiency, 185, 244, 314 Immunoelectrophoresis, 263, 269, 314 Immunogen, 166, 314 Immunogenic, 314, 321, 348 Immunoglobulins, 314, 340 Immunohistochemistry, 46, 51, 314 Immunologic, 17, 29, 87, 304, 313, 314, 349 Immunology, 17, 59, 96, 102, 108, 113, 127, 152, 178, 262, 263, 301, 311, 314, 342 Immunosuppressant, 301, 314, 326 Immunosuppression, 64, 182, 314, 323 Immunosuppressive, 182, 305, 314 Immunosuppressive Agents, 182, 314 Immunotoxins, 314, 350 Impairment, 47, 51, 271, 272, 299, 314, 325 Implant radiation, 314, 317, 318, 348, 371 Implantation, 214, 284, 314, 332 In situ, 27, 49, 195, 314 Incision, 315, 317 Incontinence, 211, 315 Incubated, 24, 114, 315 Incubation, 119, 214, 315 Induction, 46, 78, 81, 109, 208, 303, 315, 335 Infarction, 279, 315, 351 Infertility, 36, 52, 315, 335 Infiltration, 46, 147, 218, 315 Influenza, 88, 315 Infusion, 70, 85, 101, 107, 121, 131, 136, 188, 198, 315, 329, 365 Ingestion, 53, 305, 315, 342, 362 Inhalation, 166, 263, 315, 342 Inhibin, 52, 315 Initiation, 53, 54, 315, 337, 345, 359, 365 Inner ear, 315, 369 Inorganic, 70, 100, 103, 130, 208, 312, 315, 328, 363 Insecticides, 316, 338 Insight, 14, 25, 52, 70, 316 Insomnia, 191, 316 Insulin-dependent diabetes mellitus, 6, 11, 13, 95, 231, 316 Insulin-like, 83, 212, 316 Intensive Care, 18, 110, 112, 123, 132, 133, 316 Intensive Care Units, 18, 316 Interferon, 86, 149, 316
384
Albumin
Interferon-alpha, 316 Interleukin-1, 61, 316 Interleukin-2, 102, 316 Interleukin-6, 63, 117, 316 Interleukin-8, 75, 115, 116, 316 Interleukins, 217, 314, 316 Intermediate Filaments, 317, 331 Intermittent, 39, 317, 338 Internal Medicine, 7, 9, 40, 50, 122, 317, 330 Internal radiation, 317, 318, 348, 371 Interneurons, 78, 317 Interstitial, 57, 102, 147, 149, 211, 275, 276, 299, 317, 318, 330, 351, 371 Intervention Studies, 57, 317 Intestinal, 197, 213, 278, 280, 281, 296, 305, 317, 318, 323, 324, 371 Intestinal Mucosa, 278, 280, 317 Intestine, 272, 275, 283, 295, 317, 319, 359 Intoxication, 317, 369 Intrahepatic, 127, 317 Intramuscular, 308, 317, 336 Intraocular, 24, 317 Intraperitoneal, 16, 128, 317 Intravascular, 32, 317, 335 Intravenous, 16, 43, 64, 97, 177, 188, 193, 198, 258, 315, 317, 336 Intrinsic, 39, 218, 263, 272, 317 Inulin, 45, 305, 317 Invasive, 25, 33, 70, 199, 313, 317, 323, 346 Involuntary, 272, 297, 299, 317, 329, 357 Iodine, 317, 348 Ions, 180, 215, 272, 292, 294, 312, 317, 318, 327, 346 Irradiation, 206, 318, 371 Ischemic stroke, 43, 318 Isoelectric, 203, 318 Isoelectric Point, 203, 318 Isolated limb perfusion, 134, 318 Isoleucine, 53, 318 Isotonic, 188, 318, 327 Isozymes, 27, 318 J Jaundice, 23, 94, 310, 312, 318 Jejunum, 303, 318 K Kb, 240, 318 Keratinocyte growth factor, 212, 318 Keratinocytes, 316, 318 Ketoacidosis, 319 Ketone Bodies, 319 Ketosis, 54, 319
Kidney Disease, 5, 6, 10, 11, 21, 56, 58, 62, 111, 114, 119, 128, 133, 135, 202, 203, 240, 245, 248, 264, 319, 351 Kidney Failure, 8, 21, 62, 295, 305, 319, 324 Kidney Failure, Acute, 319 Kidney Failure, Chronic, 319 Kidney stone, 319, 351, 368 Kinetic, 49, 117, 319 L Labile, 204, 283, 319 Laceration, 164, 319 Lactation, 82, 96, 319 Laminin, 272, 299, 319 Large Intestine, 283, 291, 317, 319, 350, 356 Latent, 200, 319, 339, 344 Laxative, 263, 320, 327, 357 Least-Squares Analysis, 147, 320, 350 Lectin, 142, 320, 325 Leiomyoma, 300, 320, 356 Lens, 24, 269, 320 Leprosy, 99, 320 Leptin, 39, 53, 320 Lesion, 164, 286, 320, 322 Lethal, 16, 36, 129, 271, 291, 320 Leucocyte, 265, 296, 320 Leukemia, 122, 160, 244, 292, 304, 320 Levo, 320, 325 Lice, 277, 320 Life cycle, 274, 320 Ligament, 34, 268, 320, 345 Ligands, 67, 107, 115, 176, 215, 218, 320 Likelihood Functions, 320, 350 Limb perfusion, 320 Linear Models, 321, 350 Linkage, 18, 39, 41, 55, 62, 65, 82, 217, 304, 321 Linkage Disequilibrium, 19, 321 Lipase, 37, 321 Lipid A, 66, 215, 321 Lipid Peroxidation, 50, 321, 335 Lipolysis, 50, 321 Lipophilic, 95, 321 Lipopolysaccharide, 44, 307, 321 Lipoprotein, 10, 26, 37, 50, 117, 125, 139, 293, 307, 321, 322 Lipoprotein(a), 117, 321 Liposomal, 127, 193, 321 Liposome, 108, 193, 321 Liquid Ventilation, 18, 321 Lisinopril, 139, 321 Liver cancer, 16, 28, 33, 42, 63, 265, 321 Liver Cirrhosis, 33, 211, 310, 321
385
Liver Regeneration, 42, 322 Liver Transplantation, 53, 113, 126, 182, 216, 322 Lobe, 164, 268, 279, 322, 337 Localization, 34, 52, 56, 80, 131, 314, 322 Localized, 192, 261, 266, 275, 291, 295, 301, 315, 319, 322, 333, 340, 368 Locomotion, 322, 340 Locomotor, 69, 322, 354 Logistic Models, 322, 350 Longitudinal study, 36, 62, 119, 152, 322 Loop, 303, 322 Low-density lipoprotein, 152, 293, 321, 322 Lubricants, 322, 338 Lubrication, 202, 322 Luciferase, 61, 322 Lymph, 47, 174, 280, 282, 295, 322, 323, 360 Lymph node, 47, 174, 280, 322, 323 Lymphatic, 25, 295, 315, 322, 323, 325, 333, 357, 358, 363 Lymphatic system, 322, 323, 357, 358, 363 Lymphocyte Depletion, 314, 323 Lymphocytes, 41, 80, 178, 268, 289, 312, 313, 316, 320, 322, 323, 358, 363, 371 Lymphoid, 268, 287, 320, 323 Lymphoma, 22, 244, 323 Lysine, 88, 184, 198, 276, 309, 311, 312, 323, 366 Lysinoalanine, 174, 323 M Macrophage, 24, 46, 148, 178, 217, 307, 316, 323 Magnetic Resonance Imaging, 32, 70, 323 Magnetic Resonance Spectroscopy, 51, 70, 323 Major Histocompatibility Complex, 308, 323 Malabsorption, 244, 278, 323 Malignancy, 29, 323 Malignant, 16, 60, 90, 104, 163, 174, 198, 212, 244, 262, 269, 270, 321, 323, 330, 345, 349 Malnutrition, 57, 62, 264, 271, 276, 323, 328 Malondialdehyde, 114, 323 Mammary, 78, 286, 323 Manifest, 53, 219, 323 Mannitol, 161, 324 Matrix metalloproteinase, 90, 324 Mean blood pressure, 9, 324 Meconium, 46, 116, 324
Meconium Aspiration, 116, 324 Medial, 270, 324, 363 Mediate, 34, 48, 60, 61, 72, 113, 324 Mediator, 55, 200, 280, 316, 324, 341, 355 Medical Records, 72, 311, 324 Medicament, 165, 166, 190, 324 MEDLINE, 241, 243, 245, 324 Megakaryocytes, 84, 275, 324, 363 Megaloblastic, 290, 302, 324 Meiosis, 324, 328, 361, 367 Melanin, 324, 339, 367 Melanocytes, 324, 325 Melanoma, 70, 90, 121, 207, 244, 325 Melanoma vaccine, 207, 325 Melphalan, 121, 134, 162, 325 Membrane Proteins, 278, 325 Memory, 26, 268, 289, 325 Meninges, 279, 325 Menopause, 325, 343 Mental, iv, 15, 64, 240, 242, 246, 279, 280, 285, 289, 292, 299, 325, 344, 347, 354, 367, 368 Mental Disorders, 325, 344, 347 Mental Health, iv, 15, 240, 242, 325, 344, 347 Mental Processes, 292, 325, 347 Mental Retardation, 64, 246, 325 Mentors, 51, 325 Mercury, 26, 41, 289, 301, 325 Mesenchymal, 183, 296, 307, 325 Mesenteric, 31, 325, 343 Mesenteric Arteries, 31, 325 Mesentery, 325, 338, 358 Meta-Analysis, 68, 325 Metabolic acidosis, 97, 121, 326 Metabolite, 45, 146, 273, 302, 326, 344, 349 Metastasis, 46, 174, 324, 326 Metastatic, 46, 198, 326, 354 Methotrexate, 114, 122, 162, 326 Microbe, 326, 364 Microbiological, 214, 326 Microbiology, 59, 127, 262, 271, 326 Microcirculation, 55, 102, 309, 321, 326 Microdialysis, 55, 326 Microorganism, 215, 283, 326, 337, 371 Micro-organism, 168, 210, 326 Microscopy, 16, 24, 37, 45, 47, 49, 65, 67, 72, 261, 272, 311, 326 Microscopy, Atomic Force, 45, 326 Microscopy, Confocal, 65, 326 Microsomal, 71, 326
386
Albumin
Microspheres, 96, 135, 177, 179, 185, 207, 236, 326 Microtubule-Associated Proteins, 326, 331 Microtubules, 317, 327, 331, 336 Migration, 184, 327 Mineral Oil, 207, 327 Mitochondrial Swelling, 327, 330 Mitosis, 269, 327 Mitotic, 292, 298, 327, 362, 370 Mitotic inhibitors, 292, 327 Mobility, 120, 327 Mobilization, 27, 225, 327 Modeling, 42, 170, 327 Modification, 31, 38, 127, 196, 212, 304, 327, 348 Molecular mass, 186, 327 Molecular Structure, 48, 327 Monitor, 94, 95, 108, 126, 287, 327, 332 Monoclonal, 20, 21, 27, 74, 161, 174, 199, 213, 219, 312, 314, 318, 327, 348, 371 Monoclonal antibodies, 20, 27, 161, 174, 213, 314, 327 Monocyte, 109, 178, 328 Monogenic, 38, 328 Mononuclear, 178, 328, 367 Monophosphate, 60, 328 Monosomy, 267, 328 Mood Disorders, 120, 328 Morphological, 178, 216, 294, 302, 324, 328 Morphology, 24, 45, 49, 328 Motility, 16, 328, 355 Mucilaginous, 324, 328 Mucolytic, 276, 328 Mucosa, 328, 359 Mucositis, 328, 363 Mucus, 18, 128, 328 Multidose, 193, 328 Multidrug resistance, 22, 328 Multivalent, 180, 328 Muscle Fibers, 328 Muscle relaxant, 328, 330, 339, 348 Muscle Spindles, 328, 339 Muscular Atrophy, 244, 328 Musculoskeletal System, 328, 334 Mutagenesis, 29, 328 Mutagens, 328 Myalgia, 315, 329 Myasthenia, 329, 330, 348 Mycoplasma, 206, 329 Myelosuppression, 329, 370 Myocardial infarction, 72, 129, 211, 272, 287, 329, 371
Myocardial Ischemia, 116, 128, 132, 267, 329 Myocardial Reperfusion, 329, 351 Myocardial Reperfusion Injury, 329, 351 Myocarditis, 291, 329 Myocardium, 267, 329 Myoglobin, 169, 329 Myopia, 329, 350 Myotonic Dystrophy, 244, 329 N Nasal Mucosa, 315, 330 Natriuresis, 6, 267, 330 Nausea, 319, 330, 367, 368 NCI, 1, 239, 282, 330 Necrosis, 50, 88, 92, 258, 269, 275, 279, 315, 329, 330, 351 Needle biopsy, 37, 300, 330 Neocortex, 78, 330, 331 Neonatal, 23, 64, 97, 123, 184, 215, 330 Neoplasia, 17, 38, 42, 83, 244, 330, 346 Neoplasm, 330, 367 Neostigmine, 330, 348 Nephritis, 211, 330 Nephron, 14, 105, 120, 133, 305, 330 Nephropathy, 5, 6, 8, 9, 10, 11, 12, 14, 18, 19, 28, 40, 52, 55, 58, 62, 69, 104, 117, 119, 123, 124, 133, 138, 139, 146, 147, 149, 203, 210, 211, 229, 231, 248, 319, 330 Nephrosis, 310, 330 Nephrotic, 73, 85, 123, 139, 175, 224, 225, 330 Nephrotic Syndrome, 123, 139, 175, 224, 225, 330 Nervous System, 178, 184, 244, 263, 279, 324, 330, 331, 354, 360, 361, 369 Networks, 4, 330 Neural, 48, 263, 266, 300, 303, 311, 330 Neural tube defects, 300, 330 Neuraminidase, 331, 341 Neurofibrillary Tangles, 20, 331 Neurofilaments, 331 Neurologic, 45, 64, 191, 331, 365 Neuromuscular, 261, 331, 343, 367 Neuromuscular Junction, 261, 331 Neuronal, 47, 113, 184, 307, 331, 338, 355 Neurons, 45, 47, 183, 184, 289, 298, 303, 317, 328, 330, 331, 332, 360, 361 Neuropathy, 331, 338 Neuropeptide, 30, 331 Neurotoxic, 331 Neurotoxicity, 184, 331, 370 Neurotoxins, 221, 331
387
Neurotransmitter, 261, 262, 275, 281, 306, 311, 331, 332, 356, 360, 361 Neutralization, 19, 331 Neutrons, 265, 318, 331, 348 Neutropenia, 133, 332 Neutrophil, 264, 332 Niacin, 332, 366 Nickel, 180, 332 Nicotine, 224, 332 Nidation, 294, 332 Nitric Oxide, 4, 39, 72, 83, 107, 142, 332 Nitrogen, 54, 64, 232, 264, 265, 269, 299, 301, 306, 319, 325, 327, 332, 334, 366 Norepinephrine, 42, 262, 331, 332 Normotensive, 5, 9, 11, 92, 109, 138, 139, 228, 332 Nuclear Envelope, 143, 152, 332 Nuclear Pore, 332 Nuclei, 66, 84, 265, 268, 285, 294, 304, 311, 323, 327, 331, 332, 334, 346 Nutritional Status, 4, 29, 62, 116, 148, 333 Nutritive Value, 78, 81, 333 O Odds Ratio, 11, 333, 350 Oedema, 149, 194, 333 Oligo, 120, 150, 333 Oligomenorrhea, 333, 342 Oliguria, 319, 324, 333 Oncogene, 22, 244, 333, 358 Oncotic, 4, 43, 51, 194, 333 On-line, 124, 257, 333 Oocytes, 74, 146, 333 Ophthalmology, 72, 95, 125, 301, 333 Ophthalmoscope, 333 Opsin, 333, 352 Optic Disk, 125, 286, 290, 333 Optic Nerve, 333, 352 Organ Culture, 334, 364 Organ Preservation, 194, 334 Organ Transplantation, 194, 334 Organelles, 279, 288, 324, 334, 341 Organic Chemicals, 186, 334 Ornithine, 334, 348 Orthopaedic, 35, 334 Osmolality, 133, 334 Osmolarity, 324, 334 Osmoles, 334 Osmosis, 334 Osmotic, 43, 57, 83, 101, 141, 181, 206, 209, 215, 219, 264, 327, 334, 355 Osteoarthritis, 35, 211, 334 Outpatient, 9, 334
Ovalbumin, 76, 78, 79, 80, 81, 83, 86, 87, 88, 141, 147, 149, 151, 152, 334 Ovarian Follicle, 307, 334 Ovarian Hyperstimulation Syndrome, 97, 112, 116, 335 Ovaries, 335, 342, 351, 355 Ovary, 52, 177, 223, 334, 335, 342, 359 Overdose, 120, 335 Overexpress, 17, 335 Overweight, 28, 143, 335 Ovulation, 224, 268, 282, 307, 335 Ovulation Induction, 335 Ovum, 304, 320, 334, 335, 344, 357, 372 Oxalic Acid, 276, 335 Oxidants, 40, 184, 335 Oxidation, 31, 36, 37, 94, 125, 134, 173, 200, 261, 269, 274, 288, 292, 306, 321, 335 Oxidation-Reduction, 274, 335 Oxidative metabolism, 70, 263, 335 Oxidative Stress, 31, 37, 50, 122, 148, 335 Oxygen Consumption, 336, 351 Oxygenation, 18, 51, 114, 336 Oxygenator, 18, 277, 336 P P53 gene, 71, 336 Paclitaxel, 90, 145, 149, 162, 177, 336 Palliative, 336, 362 Palmitic Acid, 46, 336 Pancreas, 194, 211, 214, 261, 273, 316, 321, 336, 358, 366 Pancreatic, 211, 244, 280, 297, 336 Pancreatic cancer, 211, 244, 297, 336 Pancreatitis, 211, 336 Paracentesis, 132, 336 Parathion, 122, 336 Parathyroid, 29, 85, 185, 336, 353, 362 Parathyroid Glands, 336, 353 Parathyroid hormone, 29, 85, 185, 336 Parenchyma, 164, 336 Parenteral, 68, 103, 165, 166, 188, 193, 198, 336 Parenteral Nutrition, 68, 103, 188, 336 Parietal, 268, 337, 338, 341 Paroxysmal, 244, 267, 337 Partial remission, 337, 351 Particle, 37, 47, 72, 170, 171, 172, 208, 321, 337, 357, 365 Patch, 164, 197, 286, 337, 365 Pathogen, 315, 337 Pathologic, 61, 179, 261, 269, 273, 286, 312, 313, 337, 369 Pathologic Processes, 269, 337
388
Albumin
Pathologies, 211, 337 Pathophysiology, 38, 45, 50, 52, 337 Patient Education, 224, 248, 252, 254, 259, 337 Peer Review, 35, 137, 337 Pelvic, 337, 345 Penicillin, 184, 337, 369 Pepsin, 337 Peptic, 211, 337 Peptic Ulcer, 211, 337 Peptide Chain Initiation, 54, 337 Peptide T, 217, 337 Percutaneous, 98, 116, 165, 190, 337 Perfusion, 18, 53, 96, 117, 131, 135, 337, 364 Peripheral blood, 16, 316, 338 Peripheral Nerves, 320, 338, 343 Peripheral Neuropathy, 52, 338 Peripheral Vascular Disease, 72, 175, 338 Peritoneal, 21, 119, 232, 270, 290, 317, 333, 338 Peritoneal Cavity, 270, 317, 333, 338 Peritoneal Dialysis, 21, 119, 232, 290, 338 Peritoneum, 17, 119, 152, 325, 338 Peritonitis, 101, 154, 338 Peroxidase, 173, 180, 321, 338 Peroxide, 338 Pesticides, 126, 316, 338 Petrolatum, 295, 338 Petroleum, 302, 327, 338 PH, 54, 92, 142, 170, 338 Phagocyte, 335, 338 Phagocytosis, 24, 339 Phallic, 301, 339 Pharmacokinetic, 121, 142, 218, 339 Pharmacologic, 58, 72, 266, 308, 339, 364, 365 Pharynx, 315, 339 Phenolphthalein, 295, 339 Phenotype, 26, 45, 60, 85, 181, 185, 284, 304, 339 Phenyl, 163, 339 Phenylalanine, 339, 367 Phenytoin, 141, 231, 277, 339 Phospholipases, 339, 356 Phospholipids, 299, 321, 339 Phosphorus, 29, 232, 276, 334, 336, 339 Phosphorylase, 182, 339 Phosphorylated, 83, 124, 180, 282, 339 Phosphorylating, 76, 339 Phosphorylation, 36, 42, 63, 65, 69, 150, 339
Photoallergy, 339, 340 Photobiology, 23, 339 Photocoagulation, 282, 340 Photosensitivity, 122, 340 Phototherapy, 23, 340 Physical Examination, 15, 29, 304, 340 Physicochemical, 83, 340 Physiologic, 16, 39, 40, 60, 75, 263, 273, 308, 317, 318, 340, 345, 349 Pigment, 80, 273, 280, 324, 325, 329, 340 Pilot study, 26, 57, 65, 340 Pituitary Gland, 300, 340 Plant Proteins, 221, 340, 369 Plaque, 32, 267, 340 Plasma cells, 22, 268, 340 Plasma expander, 4, 340, 342 Plasma protein, 162, 205, 206, 264, 295, 340, 346, 355 Plasma Volume, 3, 25, 85, 176, 206, 274, 340 Plasmapheresis, 25, 91, 125, 340 Plasmids, 56, 196, 340 Plasmin, 269, 341, 364 Plasticity, 86, 309, 341 Plastids, 212, 334, 341 Platelet Activation, 27, 341, 356 Platelet Aggregation, 220, 332, 341 Platelet Factor 4, 316, 341 Platelets, 27, 30, 60, 106, 157, 219, 272, 329, 332, 341, 363 Pleural, 333, 341 Pleural cavity, 333, 341 Pneumonia, 211, 286, 341 Pneumothorax, 324, 341 Pneumovirus, 166, 341 Podophyllotoxin, 298, 341, 362 Point Mutation, 75, 341 Poisoning, 276, 297, 317, 325, 330, 342 Pollen, 342, 348 Polycystic, 223, 245, 342 Polycystic Ovary Syndrome, 224, 342 Polyethylene, 162, 163, 191, 193, 342, 360 Polyethylene Glycols, 163, 342, 360 Polyethyleneimine, 108, 201, 342 Polygeline, 102, 342 Polymerase, 167, 178, 182, 342, 345 Polymerase Chain Reaction, 167, 342 Polymers, 24, 27, 106, 163, 186, 208, 215, 342, 343, 346 Polymorphic, 65, 76, 197, 281, 342 Polymorphism, 86, 92, 105, 342 Polymyxin, 110, 342
389
Polyneuritis, 291, 343 Polypeptide, 166, 189, 196, 210, 265, 283, 296, 300, 329, 337, 341, 342, 343, 346, 372 Polyposis, 283, 343 Polysaccharide, 268, 343, 346, 368 Polyurethanes, 27, 343 Porosity, 169, 343 Portal Vein, 98, 198, 343 Posterior, 24, 266, 270, 271, 279, 292, 336, 343 Postmenopausal, 112, 343 Postnatal, 44, 343, 358 Postoperative, 101, 343 Postsynaptic, 343, 356, 361 Potassium, 14, 39, 194, 232, 264, 292, 343 Potentiates, 316, 343 Potentiating, 166, 343 Potentiation, 281, 343, 356 Practice Guidelines, 242, 343 Precancerous, 280, 343, 344 Precipitation, 56, 142, 150, 343 Preclinical, 41, 44, 64, 343 Predisposition, 219, 344 Preeclampsia, 31, 122, 154, 175, 211, 344 Pregnancy Tests, 304, 344 Premalignant, 60, 343, 344, 346 Prenatal, 294, 344 Presynaptic, 331, 344, 361 Prevalence, 6, 8, 10, 11, 12, 14, 15, 29, 35, 50, 53, 72, 111, 139, 229, 333, 344 Primary endpoint, 26, 41, 344 Primary Prevention, 56, 344 Prions, 191, 206, 344, 354 Probe, 67, 78, 120, 134, 143, 180, 326, 344 Prodrug, 90, 151, 302, 344, 349 Progeny, 216, 285, 344 Progesterone, 344, 359 Progression, 7, 10, 13, 14, 18, 21, 29, 58, 62, 229, 267, 344 Projection, 317, 332, 334, 344, 350 Proline, 283, 312, 344 Promoter, 17, 19, 42, 45, 52, 61, 63, 64, 76, 77, 79, 87, 88, 89, 171, 211, 244, 344, 350 Promotor, 345, 352 Prone, 164, 192, 345 Prophase, 328, 333, 345, 361, 367 Prophylaxis, 162, 345, 368, 371 Prospective Studies, 8, 70, 345 Prospective study, 21, 145, 322, 345 Prostaglandin, 143, 267, 345, 360 Prostaglandins A, 345 Prostate, 173, 244, 273, 345, 346, 351, 366
Prostate gland, 174, 345 Prostate-Specific Antigen, 173, 345 Prostatic Intraepithelial Neoplasia, 174, 346 Protease, 84, 174, 203, 221, 264, 346, 364 Protein Binding, 141, 346, 364 Protein C, 46, 55, 57, 63, 107, 119, 134, 165, 181, 205, 215, 264, 265, 269, 282, 321, 346, 367 Protein Conformation, 265, 346 Protein Transport, 25, 346 Proteinuria, 6, 13, 14, 15, 18, 29, 40, 62, 85, 122, 139, 225, 305, 330, 344, 346 Proteoglycans, 272, 299, 346 Proteolytic, 17, 53, 264, 265, 283, 296, 300, 341, 346, 364 Prothrombin, 346, 363 Protocol, 37, 50, 56, 57, 120, 346 Protons, 265, 312, 323, 346, 348 Proto-Oncogene Proteins, 336, 346 Proto-Oncogene Proteins c-mos, 336, 346 Protozoa, 285, 326, 347 Provirus, 59, 347 Proximal, 25, 34, 75, 82, 85, 104, 105, 292, 303, 344, 347 Psychiatry, 99, 301, 347, 369 Psychic, 325, 347, 354 Psychology, 292, 347 Puberty, 8, 133, 347 Public Health, 26, 41, 73, 242, 347 Public Policy, 241, 347 Publishing, 73, 163, 347 Pulmonary, 31, 51, 57, 65, 71, 117, 149, 172, 211, 264, 274, 276, 286, 296, 299, 309, 313, 319, 347, 360, 369, 370, 371 Pulmonary Artery, 31, 274, 347, 370 Pulmonary Circulation, 313, 347 Pulmonary Edema, 51, 57, 71, 211, 299, 319, 347 Pulmonary Embolism, 117, 347, 371 Pulmonary hypertension, 286, 347 Pulse, 70, 327, 347 Purifying, 171, 181, 215, 347 Purines, 272, 347, 355 Putrefaction, 347 Putrescine, 30, 347 Pyramidal Tracts, 299, 348 Pyridostigmine Bromide, 141, 348 Pyrimidines, 272, 348, 355 Pyrogens, 100, 348 Q Quality of Health Care, 337, 348
390
Albumin
Quality of Life, 21, 57, 62, 202, 232, 348 Quercetin, 94, 146, 152, 348 R Race, 7, 108, 129, 325, 327, 348 Racemic, 325, 348 Radiation, 172, 261, 267, 294, 296, 298, 301, 302, 303, 314, 317, 318, 348, 349, 353, 371 Radiation therapy, 261, 298, 302, 317, 318, 348, 371 Radioactive iodine, 134, 348 Radiography, 267, 304, 348 Radioimmunoassay, 7, 225, 272, 348 Radioisotope, 297, 348, 365 Radiolabeled, 115, 171, 172, 318, 348, 371 Radiological, 337, 349 Radiopharmaceutical, 172, 349 Radiotherapy, 275, 318, 348, 349, 371 Raffinose, 161, 349 Ramipril, 9, 103, 349 Random Allocation, 349 Randomization, 41, 56, 349 Randomized, 9, 12, 26, 29, 41, 43, 50, 51, 56, 111, 132, 293, 349 Randomized clinical trial, 26, 51, 111, 349 Reabsorption, 25, 43, 85, 296, 349 Reactive Oxygen Species, 13, 31, 349 Reagent, 5, 127, 200, 205, 275, 287, 292, 298, 301, 322, 335, 349 Receptors, Serotonin, 349, 355 Recombinant Fusion Proteins, 217, 350 Recombinant Proteins, 191, 212, 213, 217, 350 Recombination, 38, 285, 304, 350 Rectal, 104, 350, 360 Rectum, 269, 283, 291, 301, 303, 315, 319, 345, 350 Recurrence, 6, 280, 281, 350 Red blood cells, 193, 297, 329, 350, 354 Red Nucleus, 271, 350 Reductase, 41, 221, 326, 350, 362 Refer, 1, 283, 301, 310, 317, 322, 331, 343, 350, 365 Reflux, 133, 350 Refraction, 170, 329, 350, 357 Regeneration, 17, 42, 63, 69, 196, 212, 300, 350 Regimen, 143, 160, 293, 350, 352 Regional chemotherapy, 197, 199, 350 Regression Analysis, 53, 350 Relative risk, 261, 350 Reliability, 134, 231, 350 Remission, 177, 350, 351
Renal failure, 4, 54, 62, 210, 211, 231, 310, 351 Renal Osteodystrophy, 30, 232, 351 Renal Plasma Flow, 12, 351 Renal tubular, 27, 351 Renin, 9, 28, 39, 55, 135, 267, 351 Renin-Angiotensin System, 9, 28, 55, 135, 267, 351 Reperfusion, 47, 61, 329, 351 Reperfusion Injury, 61, 351 Reproductive system, 345, 351 Research Support, 6, 351 Respiration, 182, 277, 300, 321, 327, 351, 352 Respiratory distress syndrome, 61, 71, 123, 211, 351 Respiratory failure, 18, 211, 351 Respiratory Physiology, 351, 369 Respiratory syncytial virus, 201, 341, 352 Response Elements, 61, 352 Response rate, 42, 352 Resuscitation, 110, 111, 352 Retina, 270, 284, 286, 290, 320, 329, 333, 334, 352, 353 Retinal, 72, 290, 333, 334, 352 Retinoblastoma, 244, 352 Retinol, 352 Retinopathy, 10, 228, 290, 352 Retreatment, 84, 352 Retroviral vector, 304, 352 Reversion, 278, 352 Rheumatoid, 211, 283, 335, 352 Rheumatoid arthritis, 211, 283, 352 Rhodopsin, 333, 352 Ribonuclease, 76, 167, 352 Ribonucleic acid, 80, 353 Ribonucleoproteins, 116, 353 Ribose, 262, 353 Ribosome, 353, 366 Rickets, 353, 371 Rigidity, 340, 353 Risk patient, 56, 353 Ristocetin, 353, 369 Robotics, 52, 353 Rod, 271, 282, 353 Rodenticides, 338, 353 Roentgenography, 353, 363 Root Caries, 7, 353 Rutin, 348, 353 Rye, 222, 282, 297, 305, 353 S Saline, 25, 129, 171, 276, 353
391
Saliva, 353, 354 Salivary, 336, 353, 354, 360 Salivation, 160, 354 Saphenous, 286, 354 Saphenous Vein, 286, 354 Saponins, 151, 354, 359 Schizophrenia, 99, 354 Sclerosis, 244, 270, 283, 354 Scrapie, 344, 354 Screening, 5, 7, 10, 12, 14, 42, 52, 56, 92, 128, 229, 231, 282, 354, 368 Sebaceous, 290, 354, 371 Sebaceous gland, 290, 354, 371 Secondary tumor, 326, 354 Secretory, 80, 346, 354, 361 Sediment, 354, 368 Sedimentation, 279, 354 Segmental, 87, 129, 305, 354 Segmentation, 354 Segregation, 271, 350, 354 Seizures, 277, 337, 339, 354 Selenium, 183, 184, 354 Semen, 345, 355 Seminiferous tubule, 266, 315, 355, 357 Semisynthetic, 277, 298, 314, 355, 362 Senile, 20, 53, 87, 355 Senile Plaques, 20, 355 Sensitization, 152, 339, 355 Sensor, 200, 202, 355 Sepsis, 54, 61, 90, 326, 355 Septic, 110, 207, 270, 355 Sequence Homology, 337, 355 Sequencing, 19, 342, 355 Serine, 53, 76, 345, 346, 355, 364, 366 Serologic, 314, 355 Serotonin, 30, 331, 349, 355, 366 Serous, 295, 355 Sertoli, 214, 266, 315, 355 Sertoli Cells, 214, 355 Sex Characteristics, 347, 355, 362 Sex Determination, 245, 356 Shock, 3, 110, 181, 207, 215, 266, 312, 356, 366 Shunt, 34, 127, 356 Side effect, 177, 178, 192, 219, 235, 263, 273, 329, 356, 360, 364, 370 Signal Transduction, 36, 60, 61, 72, 278, 356 Signs and Symptoms, 351, 356, 367 Skeletal, 54, 81, 112, 148, 183, 224, 281, 282, 328, 356, 357 Skeleton, 261, 300, 345, 356, 363
Skull, 330, 356, 362 Small intestine, 281, 293, 311, 317, 318, 356, 366 Smooth muscle, 110, 264, 276, 285, 300, 311, 320, 351, 356, 357, 360 Smooth Muscle Tumor, 300, 356 Social Environment, 348, 356 Sodium, 5, 6, 25, 39, 41, 100, 140, 184, 192, 264, 275, 291, 292, 330, 349, 356, 360 Soft tissue, 275, 356, 357 Solid tumor, 177, 292, 357 Solvent, 53, 67, 165, 185, 207, 208, 280, 298, 334, 357 Soma, 357 Somatic, 22, 38, 294, 311, 324, 327, 338, 357 Sorbitol, 41, 324, 357 Sound wave, 284, 357 Spasm, 194, 211, 357, 362 Specialist, 249, 357 Specificity, 69, 71, 72, 76, 77, 87, 180, 263, 357, 364 Spectroscopic, 23, 67, 94, 146, 152, 323, 357 Spectrum, 8, 50, 174, 225, 287, 357 Sperm, 36, 105, 261, 281, 342, 355, 357 Sperm Capacitation, 36, 357 Sperm Head, 261, 357 Spermatids, 143, 152, 355, 357 Spermatocytes, 357 Spermatozoa, 355, 357 Spermatozoon, 357 Sphincters, 299, 358 Spinal cord, 47, 68, 275, 279, 281, 303, 325, 330, 331, 338, 348, 358, 360 Spleen, 16, 22, 150, 164, 207, 266, 322, 323, 358 Splenectomy, 22, 358 Splenic Vein, 343, 358 Sporadic, 352, 358 Squamous, 90, 145, 149, 296, 358, 370 Squamous cell carcinoma, 90, 145, 149, 296, 358, 370 Squamous cells, 358 Stabilization, 32, 63, 149, 208, 339, 358 Stabilizer, 188, 195, 358 Statistically significant, 10, 358 Steady state, 58, 70, 358 Steatosis, 50, 299, 358 Steel, 282, 358, 369 Stellate, 37, 358 Stem Cell Factor, 217, 282, 358 Stem Cells, 45, 89, 183, 211, 297, 358 Stent, 117, 358
392
Albumin
Sterile, 43, 171, 172, 188, 193, 204, 270, 336, 358 Sterility, 97, 113, 315, 358 Sterilization, 186, 191, 358 Steroid, 101, 183, 184, 272, 287, 306, 354, 359 Stimulant, 311, 359, 369 Stimulus, 285, 293, 294, 298, 316, 359, 363 Stool, 283, 315, 319, 359 Strand, 22, 166, 167, 342, 359 Streptococci, 76, 80, 82, 85, 87, 359 Streptomycin, 184, 359 Stress, 10, 14, 25, 31, 34, 229, 287, 330, 335, 344, 352, 359, 368 Stroke, 43, 47, 72, 93, 113, 175, 187, 220, 240, 278, 318, 359 Stroma, 47, 336, 359 Stromal, 216, 275, 359 Stromal Cells, 216, 275, 359 Structure-Activity Relationship, 350, 359 Subacute, 315, 359 Subarachnoid, 102, 211, 308, 359 Subclinical, 131, 315, 354, 359 Subcutaneous, 193, 214, 262, 293, 308, 320, 333, 336, 359 Sublimation, 204, 359 Submaxillary, 296, 360 Subspecies, 357, 360 Substance P, 326, 353, 354, 359, 360 Substrate, 23, 27, 30, 31, 92, 112, 173, 202, 296, 331, 360 Suction, 300, 360 Sulfur, 161, 167, 182, 299, 334, 360 Sulindac, 123, 360 Supplementation, 68, 117, 125, 147, 148, 149, 151, 152, 188, 360 Suppository, 342, 360 Suppression, 52, 60, 61, 87, 178, 290, 360 Suprofen, 121, 360 Surfactant, 45, 123, 177, 208, 298, 360 Survival Rate, 33, 360 Suspensions, 27, 185, 360 Sweat, 174, 290, 360 Sweat Glands, 290, 360 Sympathetic Nervous System, 267, 360, 361 Sympathomimetic, 296, 332, 361 Symphysis, 280, 345, 361 Symptomatic, 336, 361 Synapse, 262, 331, 344, 361, 366 Synapsis, 361 Synaptic, 86, 331, 332, 356, 361
Synaptic Transmission, 332, 361 Synaptic Vesicles, 361 Synergistic, 90, 361 Systemic disease, 44, 361 Systolic, 7, 10, 313, 324, 361 Systolic blood pressure, 7, 361 Systolic pressure, 7, 324, 361 T Tachypnea, 324, 361 Taurine, 184, 272, 361 Technetium, 108, 117, 131, 172, 361 Telangiectasia, 127, 245, 362 Telomere, 308, 362 Temporal, 63, 311, 362 Tendon, 34, 283, 303, 362 Teniposide, 162, 362 Terminator, 282, 362 Testosterone, 143, 152, 350, 362 Tetany, 336, 362 Thalamic, 271, 362 Thalamic Diseases, 271, 362 Therapeutics, 4, 173, 185, 212, 218, 236, 362 Thermal, 292, 331, 342, 362 Thigh, 300, 362 Thioguanine, 162, 362 Thioredoxin, 221, 362 Thoracic, 69, 95, 97, 290, 323, 362, 371 Thorium, 100, 362, 363 Thorium Compounds, 363 Threonine, 53, 337, 346, 355, 363 Threshold, 11, 313, 363 Thrombin, 30, 206, 300, 341, 346, 363 Thrombocytes, 341, 363 Thrombomodulin, 346, 363 Thrombopoietin, 217, 363 Thromboses, 68, 219, 363 Thrombosis, 32, 272, 346, 359, 363 Thylakoids, 280, 363 Thymidine, 76, 198, 363 Thymidine Kinase, 76, 363 Thymus, 155, 314, 322, 323, 363 Thyroid, 217, 317, 336, 363, 367 Thyroid Gland, 336, 363 Thyroid Hormones, 217, 363, 367 Thyroxine, 87, 88, 105, 107, 130, 264, 313, 339, 363 Tibia, 268, 363 Tissue Adhesives, 205, 364 Tissue Culture, 20, 31, 184, 364 Tissue Distribution, 178, 364 Tissue Plasminogen Activator, 44, 364
393
Tissue Transplantation, 183, 364 Tolerance, 78, 262, 305, 364 Tomography, 323, 364 Tone, 49, 332, 364 Tonicity, 309, 318, 364 Tonus, 364 Topical, 270, 298, 312, 338, 364 Topoisomerase inhibitors, 265, 364 Topotecan, 22, 162, 364 Tourniquet, 318, 320, 364 Toxaemia, 344, 364 Toxicity, 20, 58, 131, 175, 217, 232, 277, 292, 313, 325, 353, 364 Toxicologic, 33, 364 Toxicology, 58, 92, 95, 118, 121, 122, 128, 150, 181, 216, 242, 364 Toxin, 65, 95, 171, 190, 191, 213, 221, 291, 295, 314, 364, 365 Trace element, 275, 282, 332, 365 Tracer, 33, 311, 365 Trachea, 276, 339, 363, 365 Traction, 282, 365 Transcriptase, 167, 365 Transcription Factors, 61, 85, 87, 94, 146, 352, 365 Transdermal, 95, 365 Transduction, 36, 356, 365 Transfection, 38, 69, 273, 304, 365 Transfer Factor, 314, 365 Transferases, 306, 365 Transforming Growth Factor beta, 212, 365 Transfusion, 25, 90, 215, 298, 365 Transgenes, 38, 365 Transient Ischemic Attacks, 72, 365 Translation, 59, 350, 365 Translocation, 56, 63, 346, 366 Transmitter, 261, 324, 332, 361, 366 Transport Vesicles, 48, 366 Trauma, 44, 54, 110, 111, 119, 164, 272, 308, 330, 336, 362, 366 Trees, 340, 366 Trichosanthin, 151, 366 Tricuspid Atresia, 286, 366 Triglyceride, 10, 12, 67, 142, 151, 313, 366 Trisomy, 267, 366 Trypsin, 221, 264, 296, 366 Trypsin Inhibitors, 221, 366 Tryptophan, 78, 131, 283, 355, 366 Tuberculosis, 86, 87, 366 Tuberous Sclerosis, 245, 366 Tumor marker, 273, 366
Tumor Necrosis Factor, 53, 61, 68, 115, 134, 366 Tumor suppressor gene, 336, 367 Tumour, 116, 163, 303, 367 Type 2 diabetes, 9, 10, 12, 13, 28, 41, 69, 92, 103, 114, 117, 136, 138, 140, 223, 229, 367 Tyrosine, 16, 31, 36, 42, 53, 63, 65, 94, 146, 224, 367 U Ubiquitin, 331, 367 Ulceration, 337, 367 Ultrafiltration, 121, 151, 186, 215, 309, 367 Ultrasonography, 304, 367 Unconscious, 267, 367 Univalent, 312, 335, 367 Untranslated Regions, 19, 367 Uraemia, 336, 367 Uranium, 361, 363, 367 Urban Population, 12, 367 Urea, 13, 64, 85, 98, 115, 170, 274, 334, 342, 360, 367, 368 Urease, 332, 367 Uremia, 232, 319, 351, 368 Ureters, 319, 368 Urethane, 142, 368 Urethra, 345, 368 Uric, 98, 347, 368 Uridine Diphosphate, 306, 368 Uridine Diphosphate Glucuronic Acid, 306, 368 Urinalysis, 134, 248, 368 Urinary tract, 6, 49, 271, 368 Urinary tract infection, 6, 271, 368 Urinate, 368, 371 Urine, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 18, 26, 29, 37, 42, 43, 55, 62, 65, 72, 83, 108, 111, 123, 133, 134, 135, 139, 146, 203, 225, 248, 264, 269, 271, 274, 276, 287, 292, 296, 306, 307, 309, 315, 319, 330, 333, 335, 346, 368 Urine Testing, 11, 368 Urolithiasis, 49, 368 Urticaria, 266, 368 Uterus, 280, 300, 302, 320, 335, 344, 351, 368, 369 V Vaccination, 88, 160, 201, 368 Vaccine, 160, 166, 197, 201, 212, 213, 262, 277, 346, 368 Vacuoles, 295, 334, 368 Vagina, 280, 290, 351, 369 Vaginal, 91, 322, 360, 369
394
Albumin
Valine, 200, 369 Valves, 18, 369 Vanadium, 66, 369 Vancomycin, 231, 369 Vascular endothelial growth factor, 71, 112, 369 Vasculitis, 336, 369 Vasoconstriction, 211, 297, 369 Vasodilation, 267, 369 Vasodilator, 269, 275, 311, 329, 369 Vector, 64, 71, 167, 171, 365, 369 Vegetable Proteins, 340, 369 Vegetative, 208, 209, 273, 369 Vein, 188, 198, 270, 317, 332, 343, 354, 358, 369 Venom, 221, 369 Venous, 72, 116, 188, 197, 198, 270, 272, 274, 275, 279, 289, 333, 346, 366, 369, 371 Venous blood, 274, 275, 279, 369 Venous Thrombosis, 272, 369, 371 Ventilation, 117, 369 Ventricle, 179, 271, 286, 311, 347, 361, 366, 370 Ventricular, 20, 30, 118, 286, 293, 329, 366, 370 Ventricular Dysfunction, 293, 370 Venules, 274, 277, 295, 326, 370 Vertebrae, 358, 370 Vesicular, 69, 143, 152, 307, 310, 326, 346, 370 Veterinary Medicine, 241, 370 Vial, 206, 370 Vibrio, 212, 280, 281, 370 Vibrio cholerae, 212, 280, 281, 370 Villous, 278, 370 Vinblastine, 162, 370 Vinca Alkaloids, 370 Vincristine, 162, 370 Vindesine, 162, 370 Vinorelbine, 162, 370 Viral, 17, 36, 64, 76, 119, 166, 167, 168, 182, 198, 277, 315, 365, 370
Viral Hepatitis, 182, 370 Viral Load, 36, 370 Viral vector, 64, 370 Viremia, 35, 370 Virulence, 271, 364, 370 Viscera, 325, 357, 371 Visceral, 164, 338, 371 Viscosity, 46, 57, 274, 311, 371 Vitamin D, 68, 135, 353, 371 Vitellogenin, 74, 371 Vitreous, 290, 320, 352, 371 Vitro, 16, 23, 24, 35, 36, 42, 46, 52, 53, 56, 58, 59, 69, 75, 81, 83, 86, 98, 102, 114, 117, 121, 124, 130, 131, 140, 147, 148, 150, 175, 183, 184, 189, 191, 196, 207, 217, 219, 221, 274, 278, 294, 304, 310, 314, 315, 342, 353, 364, 371 Vivo, 16, 19, 20, 22, 24, 25, 31, 35, 37, 46, 47, 52, 56, 58, 60, 61, 63, 64, 72, 75, 80, 81, 100, 104, 114, 130, 134, 146, 147, 148, 152, 158, 162, 173, 176, 181, 184, 188, 201, 211, 217, 304, 310, 314, 315, 323, 326, 335, 360, 371 Void, 6, 38, 371 Vulgaris, 154, 155, 371 W Warfarin, 106, 121, 143, 192, 371 White blood cell, 136, 268, 272, 307, 315, 323, 328, 329, 332, 340, 371 Windpipe, 276, 339, 363, 371 Wound Healing, 31, 212, 300, 324, 371 X Xenograft, 104, 267, 371 X-ray, 45, 67, 278, 284, 286, 301, 303, 318, 332, 348, 349, 358, 371 X-ray therapy, 318, 371 Y Yeasts, 206, 302, 339, 372 Z Zygote, 284, 285, 372 Zymogen, 346, 372
395
396
Albumin
