White Blood Cells - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HITE LOOD ELLS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AM ES N. P ARK ER , 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., 1960White Blood Cells: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84243-4 1. White Blood Cells-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on white blood cells. 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 WHITE BLOOD CELLS ............................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on White Blood Cells........................................................................ 13 The National Library of Medicine: PubMed ................................................................................ 53 CHAPTER 2. NUTRITION AND WHITE BLOOD CELLS ..................................................................... 99 Overview...................................................................................................................................... 99 Finding Nutrition Studies on White Blood Cells......................................................................... 99 Federal Resources on Nutrition ................................................................................................. 101 Additional Web Resources ......................................................................................................... 102 CHAPTER 3. ALTERNATIVE MEDICINE AND WHITE BLOOD CELLS ............................................. 105 Overview.................................................................................................................................... 105 National Center for Complementary and Alternative Medicine................................................ 105 Additional Web Resources ......................................................................................................... 106 General References ..................................................................................................................... 111 CHAPTER 4. DISSERTATIONS ON WHITE BLOOD CELLS ............................................................... 113 Overview.................................................................................................................................... 113 Dissertations on White Blood Cells............................................................................................ 113 Keeping Current ........................................................................................................................ 113 CHAPTER 5. CLINICAL TRIALS AND WHITE BLOOD CELLS .......................................................... 115 Overview.................................................................................................................................... 115 Recent Trials on White Blood Cells............................................................................................ 115 Keeping Current on Clinical Trials ........................................................................................... 119 CHAPTER 6. PATENTS ON WHITE BLOOD CELLS .......................................................................... 121 Overview.................................................................................................................................... 121 Patents on White Blood Cells..................................................................................................... 121 Patent Applications on White Blood Cells ................................................................................. 150 Keeping Current ........................................................................................................................ 171 CHAPTER 7. BOOKS ON WHITE BLOOD CELLS.............................................................................. 173 Overview.................................................................................................................................... 173 Book Summaries: Online Booksellers......................................................................................... 173 Chapters on White Blood Cells................................................................................................... 174 CHAPTER 8. MULTIMEDIA ON WHITE BLOOD CELLS ................................................................... 179 Overview.................................................................................................................................... 179 Video Recordings ....................................................................................................................... 179 CHAPTER 9. PERIODICALS AND NEWS ON WHITE BLOOD CELLS ................................................ 183 Overview.................................................................................................................................... 183 News Services and Press Releases.............................................................................................. 183 Newsletter Articles .................................................................................................................... 185 Academic Periodicals covering White Blood Cells ..................................................................... 186 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 191 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 195 Overview.................................................................................................................................... 195 NIH Guidelines.......................................................................................................................... 195 NIH Databases........................................................................................................................... 197 Other Commercial Databases..................................................................................................... 200 APPENDIX B. PATIENT RESOURCES ............................................................................................... 201

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Overview.................................................................................................................................... 201 Patient Guideline Sources.......................................................................................................... 201 Finding Associations.................................................................................................................. 203 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 205 Overview.................................................................................................................................... 205 Preparation................................................................................................................................. 205 Finding a Local Medical Library................................................................................................ 205 Medical Libraries in the U.S. and Canada ................................................................................. 205 ONLINE GLOSSARIES................................................................................................................ 211 Online Dictionary Directories ................................................................................................... 211 WHITE BLOOD CELLS DICTIONARY.................................................................................... 213 INDEX .............................................................................................................................................. 309

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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 white blood cells 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 white blood cells, 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 white blood cells, 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 white blood cells. 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 white blood cells, 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 white blood cells. 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 WHITE BLOOD CELLS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on white blood cells.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and white blood cells, 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 “white blood cells” (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: •

Patient with Haemospermia Source: Practitioner. 244(1614): 778-783. September 2000. Contact: Available from Miller Freeman UK Ltd. City Reach, 5 Greenwich View Place, Millharbour, E14 9NN. +44 (0)171 861 6259. Summary: Although hemospermia (blood in the ejaculate) is generally considered to be a benign condition, it should be taken seriously and every effort should be made to determine the cause of the bleeding. This article reviews the care for the patient who presents with hemospermia, including the diagnostic tests, differential diagnosis, and management of these patients. Hemospermia can be caused by inflammation and infection, iatrogenic (physician induced) causes from previous surgery or instrumentation, tumors, ductal obstruction and cysts, vascular (blood system)

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abnormalities, and systemic disease or drugs; inflammatory, infectious, and iatrogenic causes are currently the most commonly seen. Diagnosis is made based on patient history, physical examination, blood and urine testing, imaging, and invasive investigations such as cystoscopy. The author cautions that the patient must be questioned directly on how the hemospermia was observed, as the sexual partner can be the true source of bleeding. The treatment of hemospermia is dependent on the cause, but in most patients the bleeding is slight and resolves spontaneously. Patients may require a great deal of reassurance that this is generally a benign condition. Patients who should be referred to a urologist include those in whom a cause cannot be identified, and those with associated hematuria (blood in the urine), infertility, painful ejaculation, pyospermia (pus or white blood cells in the ejaculate), and lower urinary tract symptoms. 3 figures. 5 tables. 10 references. •

Streptococcus Milleri: A Cause of Pyogenic Liver Abscess Source: Journal of the National Medical Association. 93(7-8): 276-277. July-August 2001. Contact: Available from National Medical Association. 1012 Tenth Street, NW, Washington, DC 20001. (202) 347-1895, ext. 267. Website: www.NMAnet.org. Summary: Anemia, leukocytosis (high levels of white blood cells in the blood), elevated abnormal liver function enzymes, hypoalbuminemia (low levels of protein in the blood), fever, and right upper quadrand abdominal pain are common signs and symptoms of liver abscesses. Mortality is high: 100 percent without treatment, and 50 to 65 percent with medical treatment. The bacteria Streptococcus milleri has been found to be associated with liver abscesses significantly more frequently than any other streptococci. S. milleri is also a common cause of liver abscess in patients with Crohn's disease. This article reports a case of S. milleri in a 47 year old patient with a history of hypertension, alcohol abuse, and tobacco smoking. The authors stress that increased awareness of S. milleri has come from better isolation of Streptococci species. The clinical importance of this awareness is that S. milleri is resistant to metronidazole. Therefore, patients with liver abscesses who receive metronidazole may not respond if S. milleri is the infecting organism. Effective antibiotics include ampicillin, erythromycin, clindamycin, and the cephalosporins. 1 figure. 1 table. 3 references.

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Alteration of Host Defense Mechanisms in Chronic Dialysis Patients Source: ANNA Journal. American Nephrology Nurses Association Journal. 17(2): 170180. April 1990. Summary: Chronic renal failure patients maintained on dialysis have an increased risk of infection. The mechanisms involved in these patients' increased susceptibility to infection are only partly understood. This article, part of a continuing education series in nursing, presents a brief overview of normal immune function and summarizes what is known about alterations in immune and phagocytic cell function in chronic dialysis patients. Specific sections discuss phagocytic cells, monocyte/macrophage kinetics and characteristics, lymphocytes, cytokine alterations, changes in white blood cells during hemodialysis, neutrophil and monocyte function, and changes in host defense mechanisms of the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients. Although it is impossible to attribute the increased incidence of infection in dialysis patients to a single problem, the cumulative effect of a variety of abnormalities could certainly be a cause for increased rates of infections in these patients. 3 figures. 2 tables. 53 references. (AA-M).

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New Allergy Test Pins Diagnosis of Celiac Disease Source: AH! Allergy Highlights. p. 4. July-August 1990. Contact: Available from Ted Klein and Company. 740 Broadway, New York, NY 10003. Summary: Despite sometimes dramatic symptoms, celiac disease can be difficult to differentiate from other malabsorption and nutritional illnesses. This article reports on a simple allergy test called rectal gluten challenge. The test is based on the key inherited flaw in celiac disease: it is caused by an allergy to gluten, a plant protein that is found in wheat, rye, and some other grains. The rectal gluten challenge involves injecting a gluten solution inside the rectum with a syringe. Six hours later, the physician takes a scraping of tissue from the rectal wall. The physician then inspects this biopsy sample under the microscope to count the white blood cells (lymphocytes) in a standardized amount of the tissue. White blood cells are attracted to an area as part of an allergic reaction. Reporting the findings on 44 patients whose diagnoses had been determined by the more difficult intestinal biopsy method, the rectal gluten test detected 90 percent of patients who had proven celiac disease, and correctly ruled out 91 percent of others who, in fact, did not have this disorder.

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Prescription for a Healthy Life: Routine Blood Tests Source: Stadtlanders Lifetimes. Issue 3: 10-11. 2000. Contact: Available from Stadtlanders Lifetimes. Stadtlanders Pharmacy, 600 Penn Center Boulevard, Pittsburgh, PA 15235-5810. E-mail: [email protected]. Summary: Many transplant recipients know that laboratory tests are needed to check the level of the anti rejection medications in their blood. Written for transplant recipients, this health newsletter article explains the additional uses of routine blood tests in monitoring for medication side effects and the function of multiple organs (not just transplanted ones). Even when the patient feels quite healthy, the laboratory tests can catch a problem or complication before it becomes serious. During the first six months after a transplant, patients are most likely to have problems with rejection or infection, so blood work is required more frequently during this time. The article reviews the blood tests which are typically performed: hemoglobin (Hgb) and hematocrit (Hct), white blood cells (WBC), platelets (Plt), prothrombin time (PT) and International Normalized Ratio (INR), blood urea nitrogen (BUN) and creatinine (Cr), liver function tests, amylase and lipase, glucose (blood sugar), cholesterol, potassium, and magnesium. The author concludes by encouraging readers to make sure they follow the recommendations of their health care team in regards to these laboratory tests used to monitor their health.

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Physiology and Cell Biology Update: Neutrophils and Renal Failure Source: American Journal of Kidney Diseases. 34(2): 384-399. August 1999. 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: Neutrophils (circulating white blood cells) have a large arsenal of powerful weapons and play a central role in host defense. However, the same weapons that protect the host can also lead to tissue damage and organ failure if not properly controlled. In many diseases and acute inflammatory disorders, important components of pathological processes (what goes wrong) are linked to the neutrophil's ability to release a complex assortment of agents that can destroy normal cells and dissolve

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connective tissue. This article summarizes the mechanisms of tissue destruction by neutrophils and the role of kidney-specific factors that promote this effect. Some potentially harmful substances such as reactive oxygen intermediates (ROIs) can contribute to additional tissue damage by activating proteases and deactivating antiproteases. Morphological studies, neutrophil depletion studies, and anti-adhesion studies provide ample evidence that neutrophils play an important role in renal (kidney) failure. Conversely, chronic renal failure (CRF) reduces neutrophil function and thereby can increase the susceptibility to infection and sepsis. 2 figures. 121 references. •

Proteinuria in Adults: A Diagnostic Approach Source: American Family Physician. 62(6): 1333-1340. September 15, 2000. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Summary: Proteinuria (protein in the urine) is a common finding in adults in primary care practice. This article offers an algorithmic approach that can be used to differentiate benign causes of proteinuria from more rare, more serious disorders. Benign causes include fever, intense activity or exercise, dehydration, emotional stress, and acute illness. More serious causes include glomerulonephritis and multiple myeloma. Alkaline, dilute, or concentrated urine; gross hematuria (visible blood in the urine); and the presence of mucus, semen, or white blood cells can cause a dipstick urinalysis to be falsely positive for protein. Of the three pathophysiologic mechanisms (glomerular, tubular, and overflow) that produce proteinuria, glomerular (the filtering units of the kidneys) malfunction is the most common and usually corresponds to a urinary protein excretion of more than 2 grams per 24 hours. However, the urine protein-to-creatinine ratio performed on a random specimen has many advantages over the 24 hour collection, primarily convenience and possibly accuracy. Most patients evaluated for proteinuria have a benign cause. Patients with proteinuria greater than 2 grams per day or in whom the underlying etiology (cause) remains unclear after a thorough medical evaluation should be referred to a nephrologist (kidney specialist). 1 figure. 6 tables. 21 references.

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Relationship Between Pyuria and Infection in Patients with Indwelling Urinary Catheters: A Prospective Study of 761 Patients Source: Archives of Internal Medicine. 160(5): 673-677. March 13, 2000. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10946, Chicago, IL 60610-0946. (800) 262-2350. Fax (312) 464-5831. E-mail: [email protected]. Summary: Pyuria (white blood cells in the urine) is universally considered as essential for identifying urinary tract infections in noncatheterized patients. However, the utility of pyuria in the catheterized patient, to identify catheter associated urinary tract infection (CAUTI), has not been adequately defined. This article reports on a prospective study of 761 newly catheterized patients; 82 patients (10.8 percent) developed nosocomial CAUTI. While catheterized, each patient was seen daily, a quantitative urine culture was obtained, and the urine white blood cell concentration was measured. The mean urine leukocyte count in patients with CAUTI was significantly higher than in patients with infections. Pyuria was most strongly associated with CAUTI caused by gram negative bacilli; infection with coagulase negative staphylococci and enterococci or yeasts produced much less pyuria. The authors conclude that in patients with short term

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indwelling urinary catheters, pyuria is less strongly correlated with CAUTI than in noncatheterized patients with UTI. Most patients with CAUTI are asymptomatic and do not have associated fever. Pyuria should not be used as the sole criterion to obtain a urine culture in a patient with a catheter. 1 figure. 3 tables. 44 references. •

Patient-Initiated Treatment of Uncomplicated Recurrent Urinary Tract Infections in Young Women Source: Annals of Internal Medicine. 135(1): 9-16. July 3, 2001. 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: Recurrent urinary tract infections (UTIs) are a common outpatient problem, resulting in frequent office visits and often requiring the use of prophylactic antimicrobial agents. Patient-initiated treatment of recurrent UTIs may decrease antimicrobial use and improve patient convenience. This article reports on a study undertaken to determine the safety and feasibility of patient-initiated treatment of recurrent UTIs. The prospective clinical trial included 172 women who, after selfdiagnosing UTI on the basis of symptoms, initiated therapy with ofloxacin or levofloxacin. The results showed that 88 of 172 women self-diagnosed a total of 172 UTIs. Laboratory evaluation showed a uropathogens in 144 cases (84 percent), sterile pyuria (white blood cells in the urine) in 19 cases (11 percent), and no pyuria or bacteriuria in 9 cases (5 percent). Clinical and microbiological cures occurred in 92 percent and 96 percent, respectively, of culture-confirmed episodes. No serious adverse events occurred. The authors conclude that adherent women can accurately self diagnose and self treat recurrent UTIs. 2 figures. 2 tables. 23 references.

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Periodontal Disease and Diabetes Source: Clinical Diabetes. 7(5): 1, 80-84. September-October 1989. Summary: The impact of periodontal disease on the diabetic patient and the special considerations when planning treatment are addressed. The types of periodontal disease and age groups primarily affected by each type are discussed along with evidence implicating bacterial activity as the primary cause of both gingivitis and various forms of periodontitis. Oral lesions can be a sign of diabetes; and studies are showing increased periodontal disease in people with diabetes. Other features of diabetes that predispose patients to periodontal disease include a decrease in the ability of white blood cells to destroy harmful bacteria, gingival vascular changes, and altered collagen metabolism. A table is provided which lists eight warning signs of periodontal disease. Dental treatments for diabetic patients are reviewed, including antibiotic treatment, root planing, scaling, and periodontal surgical procedures. Recommendations for proper follow-up treatment are presented. A list of suggested readings is included. 3 tables. 6 figures.

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Infection and Mucosal Injury in Cancer Treatment Source: Journal of the National Cancer Institute Monographs. 29: 31-36. October 2001. Contact: Available from Oxford University Press. Journals Subscription Department. Oxford University Press, 2001 Evans Road, Cary, NC 27513, USA (800) 852-7323. Fax (919) 677-1714. E-mail: [email protected]. Website: jncicancerspectrum.oupjournals.org.

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Summary: The oral and gastrointestinal mucosa acts as an important mechanical barrier that prevents local or systemic invasion by microorganisms. This article is from the proceedings of a conference on new strategies for research and improved treatment of mucosal injury in cancer patients. This presentation considers infection and mucosal injury in cancer treatment. The authors note that cytotoxic chemotherapy-induced mucosal injury (MI) of oral cavity (mouth) and intestinal epithelium occurs in many patients treated for malignancy (cancer). Compromise of the mucosal barrier can contribute to local invasion by colonizing microorganisms and, subsequently, to systemic infection. Historically, gram-negative bacteremia (bacteria in the blood) has been the most problematic bacterial infection in neutropenic (low levels of infectionfighting white blood cells) patients, but its incidence has reduced over time because of the use of prophylactic (preventive) antibiotics. There has been a shift in the type of infecting organisms responsible for bacteremia in these patients, from predominantly gram-negative organisms to gram-positive cocci. Infection can also exacerbate MI after cancer treatment. The best recognized example is herpes simplex virus type 1 (HSV1). Latent virus is frequently reactivated in HSV-seropositive patients; this reactivation leads to stomatitis (cold sores, canker sores), which can be indistinguishable from MI caused by cancer therapies. Antiviral prophylaxis or treatment can control the virusinduced MI and bring about overall easing of MI. The authors conclude that recognition of this infectious cause of MI is important in order for physicians to anticipate and minimize oral toxicity and to facilitate optimal delivery of the anticancer regimen. 2 figures. 80 references. •

Levamisole Therapy in Corticosteroid-Dependent Nephrotic Syndrome Source: Pediatric Nephrology. 11(4): 415-417. August 1997. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: This article reports on a study in which the effect of prolonged treatment with levamisole was examined in 43 patients (30 boys, 13 girls) with steroid dependent nephrotic syndrome (SDNS). Levamisole is a drug that modulates phagocytic (cells that surround and digest microorganisms and cellular debris) and lymphocytic (white blood cells that assist in immune function) activity. Nephrotic syndrome is a condition characterized by massive edema (fluid accumulation), heavy proteinuria (protein in the urine), hypoalbuminemia (low levels of protein in the blood), and susceptibility to infections. The mean age at the beginning of treatment was 4.0 years (plus or minus 2 years). Fourteen patients had previously received cyclophosphamide with an ensuring remission of 8.5 months (plus or minus 10 months). Following induction of remission with prednisolone, levamisole was administratered at a dose of 2.5 milligrams per kilogram of body weight on alternate days. Prednisolone was tapered to 0.5 milligrams per kilogram of body weight on alternate days. The duration of levamisole therapy ranged from 6 to 31 months; 15 patients received levamisole for more than 18 months and 10 for more than 24 months. Prednisolone was discontinued in 18 patients after a mean duration of 11.7 months, whereas in 21 patients, its dose was reduced to 0.2 to 0.4 milligrams per kilogram of body weight on alternate days. The mean relapse rate prior to levamisole therapy was 3.0 relapses per year, which reduced to 0.9 relapses per year during levamisole treatment. A comparison of the response in 14 patients who had previously received cyclophosphamide with the other 29 patients did not show any significant difference. There were no side effects of levamisole therapy The authors conclude that treatment with levamisole is beneficial and safe in SDNS, with a marked

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steroid sparing effect. A significant proportion of these patients can be kept in remission on levamisole alone. 3 tables. 16 references. •

Urinary Tract Infections: Disease Panorama and Challenges Source: Journal of Infectious Diseases. 183(Supplement 1): S1-S4. March 1, 2001. Contact: Available from Journal of Infectious Diseases. University of Chicago Press, Journals Division, P.O. Box 37005, Chicago, IL 60637. (773) 753-3347. Fax (773) 753-0811. E-mail: [email protected]. Website: www.journals.uchicago.edu. Summary: This article reprints a presentation that served as an introduction to a conference that reviewed new advances in the understanding of the pathogenesis (development) of urinary tract infections (UTIs) from the perspective of both the pathogen (e.g., bacteria) and the host. This initial presentation provided an appropriate context for subsequent discussion by providing an overview of the etiology and epidemiology of UTI, diagnostic and therapeutic approaches, current management strategies, evolution of antimicrobial resistance, and current approaches to prevention. A bacterial etiology (cause) can usually be demonstrated for most episodes of UTI, and the most common bacterial species seen in various patient groups have now been well defined. UTIs are still usually diagnosed by urine culture results; the authors call for the development of a rapid, accurate, inexpensive test that would allow the practitioner to decide whom to treat at the time of examination. In part due to the managed care environment, many doctors are now advocating that acute uncomplicated UTI in women be managed effectively and safely by utilizing empiric antibiotic therapy without doing a urine culture or even looking for pyuria (white blood cells in the urine). General trends in the treatment of UTIs have been toward the use of shorter regimens (even single dose therapy) and in the case of acute pyelonephritis and complicated UTI, the provision of therapy in the outpatient setting (for most patients). The authors conclude that despite considerable advances in the understanding of the pathogenesis of UTI, researchers have not yet developed new, clinically useful means for preventing UTIs. 20 references.

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UTI in Women: How Best to Treat Acute and Recurrent Infections Source: Consultant. 39(5): 1457-1460, 1463-1464. May 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article reviews recent changes in the recommended strategies for diagnosing and managing acute and recurrent urinary tract infections (UTIs) in women. Microscopically proven pyuria (the presence of white blood cells in the urine) usually can help the physician confirm the diagnosis of acute, uncomplicated UTI in patients who present with dysuria (painful urination) and urinary frequency and urgency; urine cultures are rarely necessary. Empiric, short course antibiotic therapy successfully cures most such infections. In contrast, culture and antimicrobial sensitivity testing are needed to direct management of recurrent or complicated UTIs. Physicians should also be aware of an inciting event that may trigger recurrences. Depending on the pattern of reinfection, recurrent UTIs can be managed by self medication during symptomatic episodes; for example, precoital or postcoital antibiotic prophylaxis; prophylaxis during menstruation; or long term, low dose, every other night prophylaxis. An estrogen cream may ease the dysuria and frequent urination common in elderly women. The author reiterates the need to reserve urologic evaluation, including intravenous pyelography, for suspected anatomic or functional abnormalities of the urinary tract. One chart

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provides the suggested patient care algorithm for managing recurrent, uncomplicated lower UTIs in women. 1 figure. 4 tables. 10 references. (AA-M). •

T Cell Mutiny Source: JDF International Countdown. 21(1): 34-36, 38-39. Winter 2000. Contact: Available from Juvenile Diabetes Foundation International. 120 Wall Street, New York, NY 10005-4001. (800) 533-2873 or (212) 785-9500. Website: www.jdfcure.com. Summary: This article reviews scientific efforts aimed at intervening in the process by which the immune system attacks and destroys insulin producing beta cells of the pancreas. The mechanism by which the immune system attacks and destroys these cells involves certain white blood cells called T lymphocytes. These cells infiltrate the pancreatic islets and secrete cytokines that set about destroying the beta cells. A current hypothesis is that autoimmune diseases such as diabetes result when the balance of power between autoreactive T cells and autoregulatory T cells shifts in favor of the autoreactive T cells. Although the cause of this shift is unknown, it is known that people who develop type 1 diabetes have a genetic predisposition to the disease. However, many investigators believe that something must happen in the environment to trigger it. Possible triggers include an invading virus and the loss of oral tolerance. The realization that type 1 diabetes is an autoimmune disease led scientists to test whether immunosuppressive agents could preserve functioning of remaining beta cells in people who still had some functioning beta cells. Studies revealed limited success, so scientists shifted their efforts toward earlier intervention. One promising effort is the use of low dose insulin injections before the onset of type 1 diabetes. Another approach has been to give insulin orally to produce oral tolerance. Both strategies have evolved into a large multicenter clinical trial known as the Diabetes Prevention Trial-Type 1. Another relatively benign approach to intervention involves using high doses of the B vitamin nicotinamide. Other research efforts are focusing on the beta cell protein glutamic acid decarboxylase (GAD). Findings from a study of GAD suggest that the immune response to GAD might completely block diabetes in prediabetic people as well as people who have type 1 diabetes who receive islet cell transplants. Emerging strategies for preventing autoimmune recurrence in islet cell transplantation include bone marrow chimerism, antibodies that block the function of T cells, and gene therapy.

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Hematuria: UTI or Something More Serious? Source: Consultant. 39(2): 319-322, 327, 331, 334. February 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article reviews the clinical evaluation of hematuria (red blood cells in the urine) and presents guidelines for determining its cause. Complaints of dysuria (painful urination), urgency, burning, and increased frequency in conjunction with pyuria (white blood cells in the urine) and hematuria are consistent with urinary tract infection (UTI), while a history of recent upper respiratory tract or skin infection suggests either IgA nephropathy or postinfectious (or post streptococcal) glomerulonephritis. Hematuria in conjunction with unilateral flank pain radiating to the groin may indicate ureteral obstruction. Certain medications may also cause hematuria. If the initial evaluation suggests a renal parenchymal disease, consultation with a nephrologist is warranted. Isolated asymptomatic hematuria without an obvious source warrants a genitourinary tract evaluation, especially in older patients. In younger patients, periodic reevaluation of microscopic hematuria with urinalysis is probably sufficient. Newer cytodiagnostic

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urine assays may help determine whether the cause is urologic or renal. One chart provides the suggested patient care algorithm for evaluating hematuria. 1 figure. 3 tables. 19 references. (AA-M). •

Acute Infectious Diarrhea in Adults Source: Patient Care. 33(15): 58-60, 63, 67, 70, 73-74, 76-77. September 30, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article reviews the diagnosis and treatment of acute infectious diarrhea in adults, focusing on determining when to provide supportive therapy versus a more detailed workup and targeted antibiotic therapy. Diarrhea can be defined as the passage of three or more unformed stools during a 24 hour period; the condition is acute if it persists for less than 14 days. The infectious agents that cause acute diarrhea are usually acquired by fecal oral transmission. Food may be contaminated by an infectious agent as a result of poor personal hygiene, a deficient sewage system, or by the use of inadequately purified water. The organisms most commonly isolated from patients with infectious diarrhea are Campylobacter jejuni, Salmonella species, diarrheagenic Escherichia coli, and Shigella species. Less frequent causes of diarrhea include Staphylococci, Bacillus cereus, Clostridium perfringens, Clostridium difficile, Vibrio species, and Yersinia species. The author discusses the special situation of diarrhea in patients with AIDS and briefly reviews the pathophysiology of diarrhea. For most patients with mild to moderate diarrhea, a diagnostic workup may not be necessary, and empiric, supportive treatment is usually sufficient. The author reviews the tests that may be used for more severe diarrhea, including fecal leukocyte testing, flexible sigmoidoscopy, stool culture, blood culture, ova and parasite examinations, and the C difficile toxin test. Fluid and electrolyte replacement usually are sufficient for mild diarrhea. Moderate diarrhea in adults or older children may be treated with bismuth subsalicylate, loperamide, or attapulgite. Antibiotic therapy may be appropriate for patients with febrile dysentery (fever is present), severe diarrhea with many fecal leukocytes (white blood cells in the feces), or with moderate to severe travelers' diarrhea. Specific antibiotic therapy is given when a treatable enteric pathogen is identified by stool or blood cultures. The article concludes with a section describing prophylaxis for travelers' diarrhea. 1 figure. 4 tables. 5 references.

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Guidelines for Evaluating and Treating Chronic Diarrhea Source: Consultant. 39(9): 2463-2464. September 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This article summarizes strategies for evaluating and treating chronic diarrhea, a common problem that has many possible causes. A careful patient history taking is vital for identifying the possible causes of diarrhea. The author notes that although the physical examination may not help establish the cause of the patient's diarrhea, it can help establish the severity of the problem. Serum chemistry screening can help clarify the patient's fluid and electrolyte status and nutritional status, as well as identify any liver problems or dysproteinemia. A quantitative or a spot stool collection and analysis is useful to classify the type of diarrhea, which in turn may help identify its cause and indicate a management strategy. Stool tests include sodium and potassium concentrations in stool water, stool pH, fecal occult blood test, white blood cells, excess stool fat, and laxative screening. The author outlines additional testing that may be

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recommended for patients with chronic secretory diarrhea, chronic osmotic diarrhea, chronic inflammatory diarrhea, and chronic fatty diarrhea. The author recommends that empiric therapy should be administered under specific circumstances: as an initial measure before diagnostic testing; when diagnostic test results are inconclusive; or when the patient does not respond to treatment or when no treatment is available. Because adequate hydration is essential to successful treatment, some patients may require administration of oral hydration solutions. 1 table. 1 reference. •

Rheumatoid Arthritis: How to Make the Most of Laboratory Tests in the Work-Up Source: Consultant. 38(5): 1341-1344, 1347-1348. May 1998. Summary: This journal article for health professionals reviews the laboratory tests most often used to diagnose, assess, and monitor the response to therapy among patients with rheumatoid arthritis (RA). Among the most helpful tests are erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) measurement. The ESR is a good, nonspecific indicator of inflammation; however, serial measurements of CRP are better for monitoring the course of RA and probably the response to therapy. Other hematologic studies include those measuring white blood cells and platelets. While rheumatoid factor may be found in some healthy people, a positive titer helps confirm RA, and a high titer often indicates more severe disease. The antinuclear antibody test is probably the one most frequently used to check for rheumatoid factor in patients with joint symptoms. Of all the cytokines, interleukin-6 correlates best with clinical improvement in patients who receive disease-modifying agents. To overcome the deficiencies of individual tests in monitoring disease activity, several have been incorporated in indexes, such as the Ritchie and Mallya indexes. 4 tables and 23 references. (AA-M).

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Renal Tuberculosis Presenting as a Large Perinephric Mass Source: Infections in Urology. 10(6): 171-172, 175. November-December 1997. Contact: Available from SCP Communications, Inc. 134 West 29th Street, New York, NY 10001-5399. (212) 631-1600. Fax (212) 629-3760. Website: http://www.scp.com. Summary: Tuberculosis (TB) infections most commonly affect the respiratory and genitourinary systems. In industrialized countries, between 8 and 10 percent of patients with pulmonary TB develop renal (kidney) TB, and 15 to 20 percent of the population in developing countries have Mycobacterium tuberculosis cultured from the urine. This article reports a case of a patient who exhibited an unusual case of renal TB presenting as a perinephric mass. A 56 year old man with a 3 year history of untreated hypertension presented with a 2 week history of low grade fever, 10 pound weight loss, and acute onset of right hemiparesis (muscular weakness on one side of the body). The patient had no history of TB or urinary symptoms. Muscle strength in the right arm and right leg were diminished. A 15 by 20 cm, well defined, round, nontender, mobile mass was found in the left upper quadrant and flank. Other findings on abdominal and chest exam were normal. Urinalysis revealed many white blood cells per high power field, but no bacteria. Intravenous pyelogram was performed: the upper and mid poles of the left kidney were absent on nephrogram, and delayed excretion of contrast from the lower pole was observed. The right kidney was normal. The patient underwent an uncomplicated left radical nephrectomy for suspected liposarcoma. The gross pathology revealed a hard, fibrotic mass measuring 24 by 18 by 12 cm, filled with yellow purulent material surrounding a dilated collecting system and a 2 cm calculus. The renal tissue culture grew M. tuberculosis. The patient did well postoperatively and was discharged on the fourth day after the operation. In this patient, computed tomography (CT scan)

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provided the first clue to the diagnosis by suggesting the inflammatory nature of the renal mass; the diagnosis was confirmed by culture. 2 figures. 12 references.

Federally Funded Research on White Blood Cells The U.S. Government supports a variety of research studies relating to white blood cells. 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 white blood cells. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore white blood cells. The following is typical of the type of information found when searching the CRISP database for white blood cells: •

Project Title: A CONTINUOUS SENSITIVE MAGNETIC SEPARATOR FOR CELLS Principal Investigator & Institution: Takayasu, Makoto; Center for Cancer Research; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2003 Summary: (provided by applicant): The purpose of this work is to develop a new, very sensitive magnetic separation method for biological cells. The device can continuously separate cells in a static magnetic field on the basis of high gradient magnetic separation (HGMS). The separation is a closed, sterile continuous flow process, which will be applicable to clinical usage as well as for diagnostic purposes. The magnetic separation method can selectively separate target cells from a heterogeneous cell mixture suspension. The proposed continuous magnetic separator can simultaneously increase both grade and recovery of the target product unlike a conventional HGMS magnetic separator which captures all components together in the filter, resulting in a tradeoff between grade and recovery. The continuous magnetic separation method provides a unique apparatus that is very different in operating principle from existing techniques such as centrifugation and membrane ultrafiltration. The magnetic separation process is based on the magnetic susceptibilities of cells and is very gentle, minimizing or eliminating mechanical damage to the cells. The continuous magnetic separation method does not trap cells in the separator and does not require a wash-out cycle. It can minimize clotting, coagulation and aggregation problems of blood cells. Experimental evaluation of the continuous magnetic separation to be developed under this project will be performed by selective separations of white blood cells from whole blood and plasma separation. The goal of the two-year research project is to develop a highly sensitive continuous magnetic separation device for biological cells in a range of very weak magnetic susceptibilities (+10.6) and to evaluate selectivity and recovery

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

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performance of the separator using blood cells. A magnetic separator for future applications of various biological cell separations will be designed based on the use of a high-field superconducting magnet, taking into account the minimization of stray fields. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALLOIMMUNIZATION TO PATERNAL LEUKOCYTES FOR HDN Principal Investigator & Institution: Moise, Kenneth J.; Obstetrics and Gynecology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 09-APR-2001; Project End 31-MAR-2003 Summary: (Provided by Applicant): Despite the widespread use if prophylactic immune globulin, HDN, secondary to maternal sensitization to the RhD antigen, continues to complicate 6 in 1,000 births in the United States. In severe cases, the intrauterine transfusion of red cells to the fetus can be life-saving. However, despite this technical advancement, 15 to 25% of fetuses still succumb to their anemia. The long-term objective of this investigation is to develop a unique immunologic approach to the treatment of red cell alloimmunization in pregnancy, thereby negating the need for invasive fetal therapy. Such an advance, will allow couples plagued by this disease to more likely achieve a successful outcome to their pregnancy. The first aim of this investigation is to establish an animal model for hemolytic disease of the newborn. Female rabbits will be sensitized to incompatible red cells then bred with a buck with a compatible red cell type producing a control litter. Fetal blood sampling using ultrasound guidance will be used to assess levels of fetal hemoglobin. Neonatal hemoglobins and assessment for hepatosplenomegaly will also be undertaken. The does will be bred a second time with a red cell incompatible buck producing an affected anemic litter. Fetal and neonatal assessments will be repeated. The second aim of the study will be to alloimmunize does to paternal leukocyte antigens. Bucks that are incompatible with specific does at multiple rabbit leukocyte antigen (RLA) loci will be given a series of injections with granulocyte stimulating factor to increase the circulating white blood cell pool. Multiple immunizations of the does will then be undertaken using white cells from these bucks; anti-RLA titers will de assessed using flow cytometry. The third aim of the study will be to prove that immunization to paternal RLA antigens will decrease the severity of the HDN as compared to the second, incompatible breeding. A third breeding will be undertaken with the buck that is incompatible for both red cell and RLA antigens. Fetal and neonatal assessments will be repeated as in the two prior breeding. The fourth aim of the investigation will be to determine if the antibodies to the RLA-A or RLA-D locus are responsible for the protective effect for HDN of paternal anti-RLA antibodies. Specific does will be matched to bucks for either their RLA-A or RLA-D loci before their initial alloimmunization to white blood cells. Incompatible breeding will then be undertaken. The fifth aim of the study will be to investigate the in vitro protective effects of anti-RLA antibodies. A monocyte monolayer assay will be performed using the spleens and sensitized red cells of the pups from the three serial breedings to determine the level of phagocytosis of the fetal reticuloendothelial system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTI TNF ANTIBODY IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: St Clair, Eugene W.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001

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Summary: Purpose: The purpose of this study is to evaluate the efficacy and safety of chronic Anti-tumor necrosis factor (TNF) Chimeric Monoclonal Antibody (cA2) treatment in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). Additional objectives of the study are to determine the efficacy and safety of cA2 treatment in providing continued reduction in signs and symptoms, reduction of disability, slowing of joint damage, promotion of disease remission and improvement in quality of life at 1 year following the onset of treatment. RA is a chronic autoimmune disorder of unknown etiology that occurs in approximately 1% of the population. MTX has become the drug of choice for many rheumatologists because of its superior efficacy and faster mode of action. However, despite treatment with MTX, many patients only experience partial relief of symptoms and continue to exhibit active disease. Cytokines such as TNF-a are abundant in inflamed joints and promote the influx of neutrophils into synovial fluid and entry of lymphocytes and monocytes into the synovial tissue. TNF appears to be a key mediator since it regulates other proinflammatory cytokines. Methods: Patients will be randomized into one of five treatment groups: Group I receives placebo infusions, Group II receives 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks through week 54 (with placebo infusions at the interim visits), Group III receives 3 mg/kg cA2 infusions at each visit, Group IV receives 10 mg/kg cA2 infusions at weeks 0, 2 and 6 and every 8 weeks through week 54 (with placebo infusions at the interim visits), and Group V receives 10 mg/kg cA2 infusions at each visit. The study was extended to allow for an additional 12 infusions of the same blinded dose regimen patients were randomized to in the first 54 weeks of treatment. Patients will be required to make 2 safety follow-up visits after their last infusion. Results: Study enrollment began in April of 1997 and is now complete with 25 patients randomized. Thirty-six patients were screened for the study. By race and gender, they include: 21 Caucasian females; 12 Caucasian males and 3 African American females. There were two adverse events leading to patient withdrawals in 2 cases. One patient was withdrawn due to a decrease in the number of white blood cells. This event was judged possibly related to the study medication. Follow-up studies show an improvement in this laboratory finding since termination of the study agent. This patient will not receive further treatments of the study medication under this protocol. This patient is participating in follow-up evaluations. Another patient was withdrawn because they were unable to return for the required visits after a partial lumbar hemilaminectomy on November 6, 1997. This patient was allowed, by the sponsor, to continue in the study despite the surgical event. However, a slow recovery period made this too difficult for the patient. This patient agreed to return periodically for safety evaluations, however, she has not returned for follow-up. Her husband gave permission to contact her local physician to request follow-up information on her condition. On 9/8/98, her physician informed me that he had terminated this patient from his care because of abuse of pain medications. At the time of contact this patient was in a hospital's de-tox unit for abuse of pain meds and alcohol. Her physician informed me that to his knowledge, the patient has not been diagnosed with any other autoimmune diseases, has not developed a malignancy, or developed a serious infection requirring hospitalization, and the patient was alive. No other follow-up information has been obtained since that time. Four patients were withdrawn from the study because of worsening of their arthritis or no clinical improvement in their arthritis. All four patients are participating in follow-up evaluations. An analysis of the week 30 data from the study reveals improvement of joint count tenderness and swelling as well as quality of life changes. Data also show a significant response to treatment at both dose levels. Significance: Current treatment of RA is often unsuccessful and has not been shown to prevent joint damage. The proposed study is potentially an effective treatment for RA

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because of its ability to bind to human TNF and neutralize its biologic activity. Future Plans: The sponsor of the study plans to file for FDA approval of this drug in 1999. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLOOD GENOMICS OF ANTICONVULSANT EFFICACY IN CHILDREN Principal Investigator & Institution: Glauser, Tracy A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The selection of anticonvulsant (AED) therapy for patients with epilepsy is based on the patient's seizure type and AED side effect profile. Since significant individual variation exists in the response to therapy, the ability to identify, either prior to or early in therapy, individuals who will attain long-term seizure freedom with a specific AED would represent a significant advance in epilepsy pharmacotherapy. We propose that the genomic expression of white blood cells prior to or just after drug administration will identify individuals likely to attain seizure freedom. Our preliminary data shows: (1) seizures, stroke, hypoglycemia and hypoxia produce characteristic changes of gene expression in the blood of rats 24 hours later, (2) single seizures produce different changes in gene expression in the blood of adult patients 24 hours later, and (3) valproic acid and carbamazepine monotherapy in children with epilepsy produces changes of gene expression in blood leukocytes that are different for each drug and different from controls. This study will determine if there is a blood genomic pattern associated with AEDs and their efficacy. The aims of this study will be to: (1) Determine if there are unique whole blood genomic expression patterns in children with epilepsy experiencing seizure freedom six months after the initiation of oxcarbazepine or valproic acid; (2) Determine whether there is a pattern of gene expression in whole blood prior to treatment that correlates with seizure freedom at one or six months of therapy; (3) Determine if there is a pattern of gene expression in whole blood at one month of therapy that correlates with seizure freedom at six months of therapy. The hypotheses are: (1) The blood genomic expression patterns in children with epilepsy treated with valproic acid and oxcarbazepine will differ from each other and will differ from the blood samples prior to therapy (2) The blood genomic expression patterns in leukocytes prior to therapy or after one month of therapy will predict which patients will attain seizure freedom from oxcarbazepine or valproic acid therapy. We will study whole blood total RNA using the new human U133 Affymetrix oligonucleotide microarrays that assess over 39,000 transcripts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTROL OF A ACTINOMYCETE COMMITANS LEUKOTOXIN EXPRESSIO Principal Investigator & Institution: Demuth, Donald R.; Professor; Biochemistry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-JAN-2003 Summary: Actinobacillus actinomycetemcomitans (Aa) is an important pathogen in the human oral cavity associated with localized juvenile periodontitis. The bacterium expresses several factors that may contribute to its virulence, one of which is a leukotoxin that kills human white blood cells. This might impair the immune response against Aa. Our studies suggest that the toxicity of Aa dramatically increased when a small DNA sequence was deleted from the promoter sequence of leukotoxin (ltx) operon

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or when an insertion element is present upstream of the operon. Both events result in a 10-fold increase in leukocyte expression. In the present application, we propose to determine how these events influence the overall expression of the ltx operon in Aa. This will be accomplished by evaluating the specific sequences that control ltx expression and determining if two promoters are functional in highly toxic Aa strains. We will also determine if the deletion removes a sequence that normally functions to repress ltx expression in Aa. Loss of repression may contribute to the constitutively high ltx expression found in highly toxic Aa strains. We will also investigate the mechanism whereby the acquisition of a transposable element stimulate ltx expression. We will determine if a new fusion promoter forms upon insertion of the IS element and/or if the IS element disrupts an existing regulatory sequence that controls ltx expression. Finally, we will determine if toxin-containing vesicles can function to deliver virulence factors (i.e., leukotoxin) to the target cell if concentrated form and if the elaboration of these vesicles is dependent upon the levels of leukotoxin expression. These studies will clarify the mechanism lead to the over-expression of leukotoxin in some strains of Aa and may identify potential new targets for anti-microbial therapy. This is clearly important in light of the increasing incidence of multiple drug resistant bacterial pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROLLED REPERFUSION FOR WHOLE BODY ISCHEMIC INJURY Principal Investigator & Institution: Buckberg, Gerald D.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objective is to develop a new approach to treat cardiac arrest. Currently, despite early, successful defibrillation in half the patients, the overall mortality rate is 95%. Furthermore, approximately 70% of these few survivors of whole body ischemia develop neurologic injury: we may save the heart, but lose the brain. The causative factors are inadequate treatment of the underlying cause of arrest by insufficient a) delivery of brain flow during CPR, b) restoring of heart blood supply to allow it to recover, and c) correction of the underlying cardiac cause. A novel approach will be taken to 1) promptly use the heart lung machine without opening the chest by an approach through leg vessels to mechanically, and temporarily, take over heart function, 2) change its prime pharmacologically to make a metabolic fuel for recovery, and 3) correct the underlying cause. We will use a relevant surgical model of either deep hypothermic circulatory arrest (DHCA) or lethal normothermic ventricular fibrillation for 10 minutes to cause whole body ischemia. Both insults cause high mortality and brain damage. We will present pilot studies showing complete heart and 100% brain recovery by integrating the specific aims of these three interventions. These results were achieved by use of a standard prime of the CPB circuit, and adding either a sodium hydrogen exchange inhibitor or specially filtering the white blood cells that cause reperfusion damage. We will extend the period of ischemia to two hours and show how this cardiac arrest model (that permits regional brain flow through the carotid arteries) can also be used to treat stroke. If this novel method of management is correct, the scheme of diagnosis and management of this almost always fatal cardiac arrest complex will change markedly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--BIOMARKERS FACILITY Principal Investigator & Institution: Santella, Regina M.; Professor; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001 Summary: The Biomarkers Facility provides a centralized, efficient, and cost- effective resource for receiving, handling, and storing human samples that are collected as part of research studies in molecular epidemiology and other types of cancer related research. These samples include blood, urine, and buccal cells. Coded samples are received by the facility and processed into appropriate fractions (e.g., plasma, lymphocytes, granulocytes, total white blood cells, red blood cells) and frozen in multiple aliquots in more than one freezer whenever possible. A computerized data base of the sample inventory is maintained and samples retrieved for analysis when necessary. A telephone alarm system is used to ensure sample safety and quality control procedures are in place to monitor sample conditions and data base accuracy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--CLINICAL Principal Investigator & Institution: Ballard, Roberta; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) The Clinical Core serves as the resource for clinical samples and data related to both clinical and basic studies of the pathogenesis and treatment of BPD. As the link between infants in the neonatal intensive care units and laboratories of the SCOR, the Clinical Core is the comer stone of the translational component of the SCOR program. Two groups of premature infants will be entered into protocols under the coordination of the Clinical Core. First, in an ongoing study, all premature infants equal to or less than 32 weeks gestation who require intubation in the first day of life (Group A) are enrolled in a prospective study of biochemical markers potentially related to development of BPD. Extensive clinical data are collected on the clinical course and outcome of the infants and these are entered into an established data base maintained by the Department of Biostatistics. Samples of tracheal aspirate, blood and urine are collected at designated intervals over the first 28 days of life and made available to SCOR investigators for studies of surfactant proteins, selected cytokines growth factors, and hyaluronic acid. Analyses of these results provide information on the postnatal pattern of expression and association with morbidities of the preterm newborn including BPD. In addition, specimens of lung tissue are obtained in cases of lung biopsy or postmortem and provided to SCOR investigators. In a second clinical protocol (Group B), clinical samples and data are collected on premature infants enrolled in a multicenter clinical trial of inhaled Nitric Oxide (iNO) to prevent BPD (the NO CLD study). This trial was initiated in April 2000 with NIH funding (R. Ballard, PI) and will enroll 726 infants over three years. Enrollment will be completed by March, 2004 and analysis of response by treatment group will then occur. Clinical samples will be collected before initiation of nitric oxide (or placebo nitrogen) therapy, at intervals during treatment, and after discontinuing therapy. Studies by SCOR investigators, particularly Projects 1, 6 and 4 will assess effects of iNO related to issues of efficacy, safety and mechanism of action. A future initiative of the SCOR will be to obtain white blood cells from infants for establishment of cell lines that will serve as a source of DNA for collaborative studies of candidate genes related to susceptibility for development of BPD as well as response to iNO. The large database on premature infants developed by

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the Clinical Core constitutes a valuable and unique resource for generation of new hypotheses regarding the pathogenesis of BPD as well as rigorous testing of current working models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL PHENOTYPES AND RESOURCES Principal Investigator & Institution: Vandeberg, John L.; Director; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAY-2002 Summary: The overall objective of the Clinical Phenotypes and Resources Core is to serve all projects by maintaining the blood sample collection, by providing clinical phenotype data from lipoprotein and fibrinolysis assays, and by providing statistical analyses of assays done in this core and in Core A. The lipoprotein and fibrinolysis data will be analyzed in Projects 1, 2, and 3 for evidence of genes that affect plasma levels (either mass or function, depending on the measure). White blood cells will be provided to Project 2 for DNA extraction. Blood samples will be processed and catalogued, and the components stored at -80 degreeC. An up- to-date inventory of the remaining volume of each sample will be maintained. Plasma and serum aliquots will be delivered to Program Project investigators and technical staff as needed. Lipoprotein phenotypes to determined on each plasma sample are TG, TC, and HDL-C by clinical chemical techniques; LDL size distribution by nondenaturing gradient gel electrophoresis; and Lp(a) and isoform-specific Lp(a) concentrations. Fibrinolytic phenotypes include plasma concentrations of fibrinogen, tissue type plasminogen activator (t-PA), and fibrin fragment D-dimer; and plasma activity of plasminogen. Quantitative data from blind duplicates will be monitored and evaluated. The investigators in this core will collaborate with investigators in the projects in analyzing data and preparing manuscripts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--MOLECULAR GENETICS Principal Investigator & Institution: Shields, Peter G.; Professor & Chief; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001 Summary: The Molecular Genetics Core Laboratory (MGCL) will provide an important resource to the TTURC based upon existing sample handling, biorepository and high throughput assay procedures. This core will be within Dr. Shields' Molecular Epidemiology Section the Laboratory of Human Carcinogenesis (LHC) within NCI. The MGCL is uniquely suited to provide the laboratory genetic support for existing hypotheses and to develop assays for new hypotheses. Our specific aims are: (1) to provide a certified Molecular Genetics Core Laboratory (MGCL) that ensures consistent and high quality sample handling, analysis and reporting for samples generated by the TTURC; (2) to provide sample receipt, sample processing and biorepository procedures for all TTURC samples; (3) to provide existing consistent methods for DNA extraction and genetic polymorphism analysis; and (4) to provide accurate reporting, quality control and quality assurance procedures. The MGCL will maintain CLIA certification for quality control and quality assurance, among existing procedures for accurate determination of assay results and reporting. Performing large-scale molecular epidemiology studies require experience and expertise. Our laboratory has done DNA extractions. from blood (white blood cells, blood clots and serum), buccal swabs, oral

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rinses, frozen human organ tissue (lung, liver, colon. breast), urine and paraffinembedded tissues. During the last five years, this constitutes DNA from more than 2,000 persons. Our success rates are greater than 98%. In calendar years 1996, 1997 and 1998, we performed 21 different genotyping assays for a total of 24,315 individual assays. There are different ways for laboratories to perform quality research. Ours is to maintain Clinical Laboratory Improvement Amendments (CLIA) certification. This is a government-mandated quality control and quality assurance monitoring program for clinical laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MURINE/HEMATOLOGY COAGULATION Principal Investigator & Institution: Le, Dzung; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001 Summary: The Murine Hematology/Coagulation Core's primary function is to check for hematological and related metabolic abnormalities in the different mouse strains produced by different Projects. The following tasks will be carried out by this core: 1) Identifying abnormalities in blood cell number and morphology, and abnormalities in hemostasis. Measurements will include: a) Hematological parameters: quantitation of red blood cells, white blood cells (including subsets), and platelets in whole blood. b) Hemostatic parameters: bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time. c) Fibrinolytic parameters: dilute whole blood clot lysis time. d) Anticoagulation parameters: protein C, protein S and antithrombin activities. 2) Identifying abnormalities in endothelial cell function with respect to hemostasis. The effect of genetically altered endothelial cell surface glycosaminoglycans (project #5) upon blood coagulation and fibrinolysis will be assessed by use of endothelial cell cultures derived from different tissues of control and transgenic mice. Cell surface related activities of tissue factor/VIIa, antithrombin, TFPI, and plasminogen will be measured. If the endothelium-targeted transgenic mice produced in projects #1 and 4 show evidence of thrombosis, similar studies will be carried out with the corresponding tissue cell cultures. 3) Screening for abnormalities of liver function and other metabolic derangements. A panel of chemistry tests will be established to evaluate the overall function of the liver and the metabolic status of control and transgenic mice. When abnormal test results are found in one of these screening tests, further studies will be performed as needed, in close co- operation with the individual project leaders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--PHARMACOLOGY Principal Investigator & Institution: Dorr, Robert T.; Professor of Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-DEC-2006 Summary: Description (provided by applicant) The pharmacology core service will provide several levels of service each project. These services include (1) the development, or adaptation of existing analytical procedures for detecting novel compounds in biological matrices; (2) the application of these procedures to blood, tumor and surrogate tissues such as peripheral blood white blood cells; (3) the mathematical description of the pharmacokinetics of each novel agent; and most importantly, (4) the development of pharmacodynamic correlations of each agent s

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pharmacokinetic disposition with biologic outcomes, including antitumor response and perturbation of the specific molecular target. To accomplish these goals, the service will utilize established high performance liquid chromatographic (1- IPLC) assays for analyzing novel inhibitors of l) VEGF in Project 2 (thalidomide and SU-5416; (2) heat shock protein-90 in Project 3 (17-AA-gledanamycin and chlorobiocin). For Project 1, anew gas chromatographic assay will be developed for the signal transduction inhibitor DPIEL. An existing radiolabeled wortmanin assay will be used for detecting this agent in Project 1. The data on plasma and tumor levels of these agents will be analyzed by non-compartmental methods to derive standard pharmacokinetic indices, and most importantly, the area under the plasma (or tumor) concentration x time curve, (AUC), in the tumor-bearing rodent models. Pharmacodynamic correlations will be performed for these pharmacokinetic parameters with, (1) the inhibition of Tumor growth and (2), the degree of perturbation of the molecular target. This will facilitate the overall goal of describing target AUCs which will need to be achieved in human trials of each agent, and the degree of target inhibition achieved by different doses and schedules of each novel agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DENDRITIC CELL IMMUNOTHERAPY FOR LUNG AND COLON CANCER Principal Investigator & Institution: Fong, Lawrence H.; Assistant Professor; Pathology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 06-JUL-1999; Project End 30-JUN-2002 Summary: Despite the identification of tumor-associated antigens in various malignancies, the vast majority of the antigens are at best weakly immunogenic. Explanations for this include preexisting tolerance to self-antigens, poor antigen presentation by tumor cells, and immune inhibition by mediators secreted by tumors (e.g. vascular endothelial growth factor and IL-10). Dendritic cells (DC), which are extremely efficient antigen presenting cells (APC) uniquely capable of sensitizing na ve T cells to antigen, have been used to reverse this immunologic unresponsiveness. Armed with tumor associated antigens, DC are capable of priming tumor specific immune responses in vitro and in vivo, often leading to tumor protection in various animal model systems. Recent clinical trials using DC have demonstrated that they can induce T cell and B cell immune responses against tumor associated antigens. Moreover, clinical responses have been observed in some patients. Representing less than 1 percent of circulating white blood cells, modest numbers of DC can be obtained from human peripheral blood by several techniques including density centrifugation and in vitro culture with exogenous cytokines. Advances making DC-based vaccination more potent and less complex will be required if this immunotherapeutic approach is to succeed clinically. The current proposal seeks to address several fundamental issues in DC immunotherapy in patients with lung and colorectal tumors with a peptide derived from carcinoembryonic antigen (CEA) as the immunologic target. We will explore the ability of a novel modified CEA peptide, with an amino acid substitution making it more immunogenic, to help break tolerance to this self-antigen. We will also examine approaches to increase tumor antigen delivery into DC via a targeting peptide. We will develop in vitro assays to evaluate the immunologic efficacy of these vaccine strategies. Finally, we will investigate the ability of a novel cytokine Flt3L to expand DC in vivo for DC harvesting in a clinical trial. The proposed studies will provide the foundation for simplified yet more potent DC targeted cancer immunotherapy for the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DNA ADDUCTS OF THE CARCINOGEN ACETALDEHYDE Principal Investigator & Institution: Hecht, Stephen S.; Wallin Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 18-FEB-2002; Project End 30-NOV-2006 Summary: (PROVIDED BY APPLICANT) The International Agency for Research on Cancer evaluates acetaldehyde as "possibly carcinogenic to humans" while the U.S. Dept. of Health and Human Services states that acetaldehyde is "reasonably anticipated to be a human carcinogen." These evaluations are based on convincing carcinogenicity studies that clearly demonstrate that acetaldehyde causes respiratory tract tumors in rats and hamsters when administered by inhalation. There is great potential for extensive human exposure to acetaldehyde. Cigarette smoke contains about 1 mg of acetaldehyde per cigarette, which is far greater than the concentrations of other carcinogens such as benzo[a]pyrene or tobacco-specific nitrosamines, widely assumed to be important as causes of cancer in smokers. Acetaldehyde is the major metabolite of ethanol and can reach significant concentrations in people who drink alcoholic beverages, especially if they are deficient in certain forms of aldehyde dehydrogenase. Acetaldehyde has been implicated as a cause of several cancer types associated with alcohol consumption. Human exposure to acetaldehyde can also occur in occupational and environmental settings. In spite of extensive human exposure to this carcinogen, little is known about its DNA adducts, which are likely central to its carcinogenic activity. We have recently characterized several DNA adducts of acetaldehyde including the Schiff base N2-ethylidenedeoxyguanosine, two diastereomeric l,N2propanodeoxyguanosine adducts, three diastereomeric N2dimethyldioxanyldeoxyguanosine adducts, and an interstrand G-G crosslink. These data promise to open new avenues of understanding of acetaldehyde carcinogenesis. Therefore, we propose to extend these studies in the present proposal. Our specific aims are: 1) Develop sensitive mass spectrometric methods to detect acetaldehyde-DNA adducts. These methods will be applied for analysis of acetaldehyde-DNA adducts in vitro, in laboratory animals exposed to acetaldehyde, and in humans (Specific Aims 2, 4, and 5); 2) Investigate the formation and stereochemistry of acetaldehyde-DNA adducts in vitro, using concentrations of acetaldehyde that are likely to be achieved in vivo; 3) Synthesize oligonucleotides containing the acetaldehyde-DNA crosslink adduct and investigate its repair and mutagenicity; 4) Quantify the formation and persistence of acetaldehyde-DNA adducts in rats or mice exposed to acetaldehyde or ethanol; 5) Quantify acetaldehyde-DNA adducts in white blood cells of humans exposed to acetaldehyde. These studies will be carried out in smokers, non-smokers, casual drinkers, and people with alcohol dependence. The results of the research proposed here will provide critical data, which will be the framework for testing our hypothesis that acetaldehyde is a human carcinogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY ARENAVIRUSES

RESPONSE

TO

HEMORRHAGIC

FEVER-CAUSING

Principal Investigator & Institution: Salvato, Maria S.; Professor; None; University of Md Biotechnology Institute Baltimore, Md 212023101 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Our application will address the need for diagnostics to identify infection with a virulent hemorrhagic fever virus, Lassa fever

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virus (LASV). Within hours of entering the body, pathogens elicit responses from circulating white blood cells. The pathogen's capacity to alter cellular gene expression can be monitored by analysis of cellular RNA. Our approach has been to expose a standardized culture of white blood cells to a pathogen and to monitor changes in cellular mRNA expression on gene microarrays. Preliminary studies with select agents revealed several pathogen-specific changes in gene expression. Here we propose to expand our analyses to a hemorrhagic fever-causing arenavirus, Lassa Fever virus. We will test the hypothesis that we can discriminate between a dangerous hemorrhagic fever-causing virus and closely related viruses that do not cause disease. By monitoring gene expression responses at different timepoints we will determine the earliest time at which pathogen-specific gene expression signals arise. These gene-expression changes can be validated by the analysis of RNA from human and monkey peripheral blood mononuclear cells (PBMCs), and will serve as diagnostic markers of exposure to dangerous pathogens. Sets of genes will be identified that discriminate infection with Lassa Fever virus from infection with a related avirulent arenavirus, and these genes will be used to make smaller microarrays to further streamline diagnosis. Such diagnostics would eliminate the need to wait for symptoms or for pathogen replication before identifying the pathogen. This would enable more appropriate and rapid responses to a bioterrorist attack. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SHIGATOXIN-1 ON BRAIN ENDOTHELIAL CELLS Principal Investigator & Institution: Kohan, Donald E.; Chief, Division of Nephrology; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from the application) HUS is the leading cause of acute renal failure in children and is characterized by renal injury, microangiopathic hemolytic anemia, and thrombocytopenia. Although the kidney is an initial target in HUS, those patients who die from the disease do so primarily from brain, not renal, involvement. There is, however, very little understanding of how the central nervous system is affected in this disorder. HUS is associated with enteric infection by Shiga toxin (Stx) producing E. coli. The toxin binds to cells expressing a specific glycosphingolipid cell surface Stx receptor (Gb3) whereupon it may exert a variety of effects, including inhibition of protein synthesis, induction of apoptosis, regulation of vasoactive factor production, and others. Generally, these studies have focused on cells thought to be primary targets in HUS, namely, renal cells. Very little work, however, has been done on how Stx affects the brain. Preliminary studies from our laboratory indicate that human brain microvascular endothelial cells (HBEC) might be targets of Stx action. Further, these studies suggest that HBEC may respond to Stx and factors likely to be present in the setting of HUS in highly unique manner. Based on these findings, the following hypothesis has been formulated: Unlike renal endothelial cells, HBEC are not normally sensitive to Stx. Soluble or cell-associated members of the inflammatory cytokine superfamily, derived from circulating white blood cells or endothelial cells themselves, cause massive upregulation of Stx responsiveness in HBEC. Such upregulation leads to enhanced white blood cell and possibly platelet adhesion, endothelial cell apoptosis and necrosis, and altered vasoactive factor production. The unique responsiveness of HBEC to cytokine upregulation of Stx-1 sensitivity may provide the basis for therapeutic interventions aimed at blocking cytokine actions on the brain. Accordingly, the specific aims are: 1) Determination of HBEC sensitivity to the cytotoxic and protein synthesis inhibitory effects of Stx-1; 2) Determination of inflammatory factor regulation of the

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cytotoxic effect of Stx-I in HBEC; 3) Determination of the source(s) of inflammatory cytokines that affect HBEC responsiveness to Stx-1, focusing on HBEC and circulating white blood cells; and 4) Determination of the effects of Stx-1 on HBEC that could lead to CNS dysfunction in HUS, including mechanisms of cytotoxicity, regulation of vasoactive factor production, and modulation of platelet adherence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS HYPERLIPIDEMIA

OF

SIMVASTATIN

ON

POSTPRANDIAL

Principal Investigator & Institution: Illingworth, D Roger.; Associate Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001 Summary: This research will study patients who have combined hyperlipidemia (increased blood levels of cholesterol and triglycerides). The study aims to look at the effects of simvastatin (Zocor) an approved drug for the treatment of hypercholesterolemia in patients who have elevated levels of blood cholesterol and concurrently moderately increased levels of blood triglycerides. Ten to twelve patients will be enrolled in the study at OHSU and it is planned to study a total of 50-60 patients at other participating centers in the United States. The purpose of this study is to assess how the body uses fats that may be eaten during the day and how the cholesterollowering drug simvastatin (Zocor) may reduce these fats in the blood after a fat-rich meal similar to a large milk-shake. We are also interested in assessing the effects of simvastatin on the body's production of cholesterol which will be measured by determination of the concentrations of a precursor of cholesterol which is excreted in the urine and how treatment with simvastatin affects the ability of white blood cells to take up cholesterol from the blood. We are also interested in measuring two enzymes known as lipoprotein lipase and hepatic lipase, which are responsible for the removal of the particles in the blood stream that contain cholesterol and other fats including new fat that enters the body after people have eaten a meal. We are trying to find out if treatment with simvastatin in addition to reducing concentrations of LDL cholesterol and triglyceride-rich lipoproteins can enhance clearance of fatty particles from the blood stream after ingestion of a fatty meal. These cholesterol-rich lipoproteins may increase the risk of developing atherosclerosis (the most common form of heart disease) and if simvastatin is shown to enhance their clearance this would be potentially of therapeutic benefit in reducing the risk of heart disease in patients with high blood levels of cholesterol and triglycerides. Until recently the maximal recommended dose of simvastatin for use in the treatment of hypercholesterolemia was 40 mg per day but a higher dose (80 mg per day) was approved in July 1998 by the FDA for the treatment of hypercholesterolemia and has been given to about 1,500 patients for a period of up to one year with a good safety profile. Participants in this study will receive three treatment periods, one of which will be a placebo, one will be simvastatin 20 mg per day and the third will be simvastatin 80 mg per day. Neither the participant nor the investigators will know which treatment is received although this information can be available if medically necessary. Participants will be asked to take two tablets of medications (a combination of simvastatin and placebo) once daily in the evening for a total period of 24 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENTAL TRIGGERS OF TYPE 1 DIABETES Principal Investigator & Institution: Simell, Olli G.; Turku University Central Hospital Kiinamyllynkatu 4-8 Turku, Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-DEC-2007 Summary: (provided by applicant): To identify environmental triggers of type 1 diabetes (T1D) we have screened genetic T1D risk so far in > 60,000 consecutive newborns at the JDRF Center for Prevention of Type 1 Diabetes in Finland (cities of Turku, Oulu and Tampere; 11,000 annual births) using HLA-DQ gene alleles that associate with risk to or protection from T1D. Those with increased genetic risk and their at-risk siblings are invited to follow-up (3- to 12-month intervals). At this writing, >8,000 high-risk children are in regular follow-up; the oldest children followed from birth are now >7.4 years of age. 474 children have developed ICA, the autoantibody used in the primary screening of follow-up samples, alone (~ 50 % of the children) or in combination with other autoantibodies (~50 %; ICA with IAA, GADA or IA-2A). 64 of the screened children have progressed to T1D; 45 of them were in tight follow-up. If a child becomes ICA positive, all four autoantibodies are measured in child's all collected and future samples, to determine the time of expected onset of the autoimmune attack and to follow disease progression. We collect demographic, medical and life event data. We offer here our huge data and sample banks for collaborative studies. The samples comprise DNA (blood spots) on filter paper and as frozen blood; serum drawn at each follow-up visit; and isolated white blood cells, living white blood cells, RNA from peripheral blood, selected blood cells and other tissues for RNA and other analyses, and stool samples at monthly intervals from children with high genetic risk. The approach is well accepted by the population, as >70% of the at-risk children remain in the follow-up at least for 7 years. The study infrastructure is firm and well-functioning at all three participating Clinical Centers. Large numbers of children represent different stages of T1D development, allowing rapid collection also of new types of samples according to need. Finland's record-high annual TID incidence of 50/100.000 children below the age of 15 years markedly increases cost-efficiency of the case finding. DIPP approach has already proven its value in exploring the role of environmental triggers in T1D development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITOPE SPECIFIC T LYMPHOCYTES IN RELAPSING EAE Principal Investigator & Institution: Jones, Richard E.; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract): The long-term objective of the proposal is to understand the immune mechanisms responsible for the relapsing episodes of paralysis which occur in patients with multiple sclerosis (MS). The debilitating paralysis of MS results from damage initiated by certain white blood cells (myelin-specific T lymphocytes) that have become harmful within the spinal cord. Following an episode of paralysis, a patient with MS may experience temporary remission or recovery from paralysis, which may in turn be followed by a relapse or worsening of the paralysis. Such a remitting/relapsing clinical course is often associated with a progression of the severity of the disease. Currently, there are few effective treatments available to MS patients (over 300,000 Americans). Experimental autoimmune encephalomyelitis (EAE), is an experimental autoimmune disease in laboratory rats and mice that is similar to MS. Studies in EAE suggest that initial episodes of paralysis and subsequent relapses may involve distinct clones of T lymphocytes, each specific for a distinct target (epitope) in

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the CNS. However, requirements of distinct, multiple clones of epitope-specific T cells in relapsing EAE have not been tested experimentally. Such information would benefit efforts to develop effective, specific immunosuppressive therapies since treatments designed to inhibit distinct T cell populations or clones are likely to be the most effective in MS if the targeted cells are actually required for the disease. For this proposal, EAE will be induced in T cell-deficient mice with single or multiple clones of myelin epitopespecific SJL or [SJL X SCID]F1 mouse T cells in order to define requirements for single and multiple clones of T cells in relapsing EAE. In Aim 1, clones of myelin epitopespecific T cells will be generated and characterized. In Aim 2, requirements for epitopespecific T cells in relapsing EAE will be defined by examining the course of disease induced with single or multiple T cell clones in lymphocyte deficient (SJLXSCID) mice. In Aim 3, the in vivo function of T cells in the CNS will be assessed during disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHNICITY, BODY COMPOSITION, BONE DEN AND BREAST CANCER Principal Investigator & Institution: Chen, Zhao; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract). Recently two studies reported a strong association between high bone mass and increased risk of breast cancer. According to the applicant, this result raises new questions in decision-making for HRT and suggests a potential use of bone mass as an indicator of lifetime estrogen exposure for assessing risk of breast cancer. Additional studies in different ethnic groups appear warranted, because there is significant ethnic variation in frequencies, distributions and severity levels of both osteoporosis and breast cancer. Given the fact that the bone mineral density (BMD) is higher, but the rate of breast cancer is lower in Hispanic older women compared with Anglo women, the Hispanic postmenopausal women would be a model to further evaluate the relationship between breast cancer and bone mass. To date, most knowledge of risk factors of osteoporosis and breast cancer is mainly based on results from Anglo women. It is critical to examine those risk factors in the Hispanic population in order to form specific prevention strategies for this population. The Women's Health Initiative (WHI) provides a unique opportunity to undertake nested case-control studies (NCCS) to further examine these issues in different ethnic groups. However, within the WHI there will not be a sufficient number of breast cancer cases to form a NCCS in Hispanic women, both because the number of Hispanic women in the WHI BMD study cohorts is small (expected n=800) and because breast cancer rate is lower in Hispanic women compared with Anglo. The proposed study is a case-control research design. The controls will be chosen from the Hispanic participants of the Arizona WHI observation study group. No additional data will be collected from the controls. The case (n=140) will be newly diagnosed Hispanic postmenopausal breast cancer patients in Arizona (obtained through collaborative oncologists and surgeons). Measurements will include anthropometry, body composition, BMD, peripheral white blood cells and WHI questionnaires. The relationship between BMD and breast cancer will be evaluated using logistic regression analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT Principal Investigator & Institution: Lipkowitz, Michael S.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (adapted from the application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the AfricanAmerican Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and understudied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FAMILIAL INTRACRANIAL ANEURYSM STUDY Principal Investigator & Institution: Broderick, Joseph P.; Professor and Chair; Neurology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Our long-term objective is to identify susceptibility genes that are related to the formation of intracranial aneurysms (IA). Rupture of IAs occurs in 16,000 to 17,000 persons in the U.S. annually, and nearly half of affected persons are dead within the first 30 days. An additional 6,000 to 7,000 persons with unruptured IAs are identified each year. Accumulated evidence indicates that a genetic component plays an important role in the development of IAs, but specific loci affecting the risk of IA have not been identified. The primary hypothesis of this study is that there are specific human chromosomal regions that are associated with an increased risk of IAs. Specific Aims of the proposal are: 1. Recruitment of 400 families with multiple individuals who have an IA through 23 referral centers throughout North America,

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Australia, and New Zealand that represent 35 recruitment sites. 2. Ascertainment of interviews and blood samples from all affected family members, as well as their firstdegree relatives. White blood cells from living persons with an IA will be cryopreserved at Cornell Institute for Medical Research for future immortalization of cells lines as indicated. 3. Identification of unruptured IAs by obtaining MRAs in selected asymptomatic siblings (of affected individuals). 4. Completion of a 10 cM genome series in persons with IAs, as well as the spouses and children of persons with an IA who are deceased. We will perform finer mapping of chromosomal regions with suggestive evidence of linkage in the genome screen. 5. Performance of a nonparametric (allele sharing) linkage analysis, including relevant environmental factors such as smoking, to identify chromosomal regions linked to IA. Reconstruction of the genotypes of deceased affected family members will be performed. Identification of individuals who are genetically at high risk for the development of IAs would enable targeted and effective screening/prevention/treatment strategies to reduce the substantial mortality and morbidity associated with this devastating type of stroke. Only a multidisciplinary, collaborative effort to identify, accrue, and genotype FIA families will be successful in identifying sufficient high-risk families to characterize the genetic basis of IA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES EXPRESSED IN NORMAL OR GROWTH ACTIVATED CELLS Principal Investigator & Institution: Krueger, James G.; Professor of Dermatology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001 Summary: The purpose of this research is to identify genes which are aberrantly expressed in human skin during wound healing. Since, blood cells accumulate in skin, it is also necessary to study genes expressed in blood-derived cells (particularly white blood cells). In order to study gene expression, skin tissue and blood will be collected for laboratory analysis. As normal values for gene expression must be established in these tissues, some individuals who participate in these studies may be normal volunteers. Furthermore, some patients who are undergoing treatment of immune-mediated skin diseases with anti-inflammatory agents may have changes in gene expression that are related to healing of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF THE METABOLIC SYNDROME IN JAPANESE AMERICANS Principal Investigator & Institution: Austin, Melissa A.; Professor; Epidemiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-MAY-2003 Summary: (Adapted from Investigator's Abstract) The long-term goal of this project is to understand genetic susceptibility to cardiovascular disease (CVD) and non-insulin dependent diabetes mellitus (NIDDM) in Japanese-American kindreds by characterizing the genetic basis of the risk factors of the metabolic syndrome (insulin resistance syndrome). During the first four years of the project, three specific aims are being addressed, as follow: 1) to determine if variation in the diameter of the major lowdensity lipoprotein subclass (LDL size) is inherited as a single gene trait in JapaneseAmerican families, and to determine if LDL size is associated with risk factors of the syndrome; 2) to characterize the inheritance of lipoprotein (a) and apolipoprotein (a) isoforms in Japanese Americans; and 3) to establish a repository of white blood cells

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and plasma aliquots for genetic studies. These aims will be accomplished by the end of the initial 4-year project period, based on data from 400 study participants, including pedigree information, extensive laboratory results, medical history questionnaire data and nutritional data. The project proposed here will enhance these studies by recruiting and sampling approximately 350 additional relatives of local, married-in JapaneseAmerican spouses, with 3 new specific aims: 1) to identify genetic influences on the risk factors that characterize the syndrome (including fasting insulin, proinsulin, C-peptide and glucose; body weight and waist circumference; lipoproteins; blood pressure; fibrinogen, factor VII and plasminogen activator inhibitor-1) using statistical genetic analysis approaches, including univariate complex segregation analysis, factor analysis, and quantitative multivariate genetic analysis; 2) to test for genetic linkage between specific candidate genes involved in lipid metabolism, carbohydrate metabolism, blood pressure, obesity, and hemostasis with genetically influenced risk factors of the metabolic syndrome in Japanese-Americans, using established linkage analysis approaches in sibships and in kindreds; and 3) when the DNA repository has been completed (750 samples by the end of year 4), to apply to the NHLBI Mammalian Genotyping Service to perform a whole genome screen to identify new genes involved in susceptibility to the metabolic syndrome. The investigators state that the studies proposed in this renewal application represent effective ways to characterize genetic susceptibility to the metabolic syndrome and subsequent risk of cardiovascular disease and non-insulin-dependent diabetes among Japanese-American families, and may lead to targeted intervention strategies to prevent these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GW433908 VERSUS AMPRENAVIR IN SUBJECTS WITH HIV-1 INFECTION Principal Investigator & Institution: Pollard, Richard B.; Professor; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001 Summary: This is a clinical research study of a new investigational anti-HIV medication, GW433908. GW433908 is a new form of amprenavir, a protease inhibitor, used to treat HIV infection. The current form of amprenavir requires patients to take a large number of capsules. GW433908 gets into the body more easily and reduces the number of pills patients have to take. The purpose of this study is to find the best dose of GW433908. This will be done by determining which dose of GW433908 gives similar blood concentrations to the marketed dose of amprenavir capsules. Eligible study subjects receive an experimental combination of abacavir, lamivudine and GW433908/amprenavir. Abacavir and lamivudine are from the nucleoside reverse transcriptase inhibitor (NRTI) class and amprenavir and GW433908 are from the protease inhibitor class of anti-HIV drugs. Both classes block enzymes that are necessary for the HIV virus to make copies of itself. With the exception of G@433908, the medications used in this study have been shown to decrease the amount of HIV virus in the blood and increase the CD4+ lymphocyte counts (white blood cells that fight off specific infections). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEALTH EFFECTS OF PAH & ETS IN MINORITY WOMEN & NEWBORNS Principal Investigator & Institution: Perera, Frederica P.; Assistant Professor; None; Columbia University Health Sciences New York, Ny 10032

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Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2001 Summary: There is increasing evidence that people of color are disproportionately exposed to numerous environmental hazards, including hazardous air pollutants such as polycyclic aromatic hydrocarbons (PAH) and environmental tobacco smoke (ETS). The Washington Heights and Harlem neighborhoods in Manhattan are typical of other Hispanic and African American communities in that they are located in a large sprawling metropolitan area characterized by elevated air pollution. The incidence of low birth weight is higher among African Americans living in Central Harlem and Hispanics living in Washington Heights than in Caucasians in the U.S. Cancer rates are also higher in African Americans than in Caucasians. Environmental risks to the developing infant are of particular concern, given the likelihood of increased susceptibility during this period. A molecular epidemiologic cohort study of African American and Hispanic mothers and newborns is proposed to investigate the role of PAH and ETS in procarcinogenic and developmental damage. A combination of personal monitoring, questionnaire and biomarkers in peripheral blood will be used to quantify individual exposure to the toxicants of concern. The biomarkers include PAHDNA adducts in white blood cells (an indicator of PAH exposure and procarcinogenic genetic damage) and plasma cotinine (a metabolite of nicotine and internal dosimeter of ETS). Measures of development will be assessed in the infants at birth and at 6 and 12 months. The proposal is responsive to concerns about environmental justice and to the recommendation of the National Research Council that risk assessment and public health policy pay special attention to the protection of young infants and children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HPV AND MRPS IN ORAL CANCER PATHOGENESIS Principal Investigator & Institution: Palefsky, Joel M.; Professor of Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 30-NOV-2005 Summary: The molecular pathogenesis of oral cancer remains poorly understood. A substantial proportion of oral dysplasias and cancers, but not all, are associated with human papillomavirus (HPV) infection. A better understanding of the mechanisms underlying HPV+ and HPV-oral disease incidence and progression is needed to develop new approaches to this highly lethal disease. The focus of this project is on the role of two novel cellular proteins, macrophage inhibitory factor-related protein (MRP)-8 and MRP14 in the pathogenesis of oral cancer. MRP8 and MRP14 are members of the factorrelated protein (MRP)-8 and MRP14 in the pathogenesis of oral cancer. MRP8 and MRP14 are members of the S-100 calcium binding protein family. They have been shown to have multiple intracellular and extracellular functions in white blood cells, but their biology in normal and neoplastic oral epithelium has not yet been studied. MRP8 and MRP14 may regulate intracellular calcium levels and play a role in calciumdependent signaling pathways in both MRP14 may regulate intracellular calcium levels and play a role in calcium-dependent signaling pathways in both HPV+ and HPV-cells. In HPV+ cells, the MRP8/14 may regulate intracellular calcium levels and play a role in calcium-dependent signaling pathways in both HPV+ and HPV- cells. In HPV+ cells, the MRP8/14 complex may inhibit casein kinase II-mediated phosphorylation of the HPV E7 oncoprotein thereby attenuating its function. We have shown that MRP8 and MRPP14 levels vary considerably depending on the stage of oral disease. In normal epithelium, MRP8 and 14 expression are low, but are highly up-regulated in low-grade dysplasia. However, high-grade dysplasia and cancers are associated with loss of expression of MRP8 and/or MRP14. We hypothesize that MRP8 and MRP14 inhibit cell

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growth through a variety of mechanisms and that up-regulation of MRP8 AND mrp14 represents a cellular response to events initiating low-grade dysplasia, such as HPV infection. We also hypothesize that loss of expression of MRP8 and/or MRP14 represents a step in oral disease progression. Accordingly, we have four specific aims: 1) To analyze expression of MRP8, MRP14 and effect of MRP proteins on HPV+ and HPVoral epithelial cell lines; 3) To determine the effects of the MRP8/14 complex on the phosphorylation and function of the HPV E7 protein; and 4) To study the effects of the MRP8/14 complex on HPV+ and HPV-oral cancer cell growth in the nude mouse model. This project will advance our understanding of the role of MRP8 AND mrp14 in oral dysplasia and cancer if our hypotheses are confirmed, manipulation of MRP expression in oral dysplasia and cancer may represent a novel therapeutic approach to treatment of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN LYMPHOCYTE ACTIVATION--ROLE OF DENDRITIC CELLS Principal Investigator & Institution: Steinman, Ralph M.; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001 Summary: Dendritic cells are a trace subpopulation of white blood cells. When antigens are presented on dendritic cells to the immune system, strong immune responses are induced. Methods have been developed to isolate dendritic cells from human blood, inflamed joints and skin. We use dendritic cells to study different aspects of the immune response in transplantation, arthritis, psoriasis, and resistance to tumors and infectious disease (influenza, AIDS). Our aims include: a) Develop monoclonal antibodies and DNA probes to cell surface and intracellular constituents of dendritic cells. b) Outline the range of inflammatory cytokines and cytokine receptors that are made by dendritic cells from blood and from diseased tissues. c) Clone T cells that may mediate autoreactivity in rheumatoid arthritis and psoriasis, and protective immunity in tumors, influenza, and AIDS. d) Study the transmission of a cytopathic infection with the AIDS virus from dendritic cells that have been exposed to the virus (HIV-1) to CD4+ T cells. Compare dendritic cells isolated from blood, skin, and inflammatory sites. Test the effect of different types of immune T cells and anti-HIV antibodies on this transmission. Generate HIV-specific immune T cells of both CD4 and CD8 subsets. Evaluate the effects of immune T cells on HIV-infected monocytes. e) Develop methods for generating large numbers of dendritic cells from immature progenitors, and use these to present antigens from tumors and infectious agents (influenza, HIV-1) to human T cells. f) Evaluate mechanisms whereby dendritic cells present superantigens to T cells, including attempts to identify superantigens that may be carried by dendritic cells in autoimmune disease. g) Evaluate in human allogeneic bone marrow chimeras the ontogeny and kinetics of dendritic cell engraftment, the role of dendritic cells in immune reconstitution, and the identification of dendritic cell progenitors and conditions supporting their growth. h) Use dendritic cells to generate antigen-specific cytolytic T lymphocytes (CTLs) to viral, tumor, and auto antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDIOPATHIC NEUTROPENIA IN NEONATES Principal Investigator & Institution: Juul, Sandra; University of Florida Gainesville, Fl 32611

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Timing: Fiscal Year 2001 Summary: The purpose of this study is to determine the cause of neutropenia in premature infants of less than 32 weeks gestation. The study will determine whether the cause of neutropenia is due to not making enough white blood cells, or using them up quicker than usual. It will also determine whether these babies are at greater risk than usual for infections and whether they respond to a medicine that stimulates white blood cell production (rG-CSF). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE MECHANISMS OF RED CELL ALLOIMMUNIZATION Principal Investigator & Institution: Campbell-Lee, Sally A.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (Applicant's abstract) Dr. Sally Campbell-Lee is an African-American physician who has completed fellowship training in Transfusion Medicine, and will be the principal investigator on this award. Drs. Paul Ness and William Baldwin, both of the Department of Pathology at Johns Hopkins, will serve as co-mentor and primary mentor, respectively. The clinical and research programs at Johns Hopkins Medical Institutions provide a rich environment for the growth and development of young investigators, with many resources at their disposal. Dr. Campbell-Lee's career goals are to become an independent investigator specializing in immune mechanisms of alloimmunization in transfusion in transfusion, in addition to serving as a medical director of a hospital blood bank and transfusion medicine service. This award will aid in reaching this goal by providing Dr. Campbell-Lee' with additional training in immunological research methods, and the use of animal models in examining mechanisms of alloimmunization, the application of which will provide insight into a longstanding problem in transfusion medicine, that of immune modulation in the transfusion recipient. The research project will investigate immune mechanisms of red cell alloimmunization in transfusion. When red blood cells (rbc) are transfused, the recipient may become alloimmunized to foreign red cell antigens. When alloimmunization occurs, the specificity of the antibody must be identified, and blood must be found that lacks the corresponding antigen for that patient. This is labor intensive and costly, and can cause a significant delay in the availability of blood. In order to develop prevention or treatment for this problem, immune mechanisms regulating antibody formation must be better identified. We will study the following using a murine transfusion system: the effects of eliminating or modifying targeted subpopulations of donor white blood cells alloimmunization to rbc antigens; the effect of coating rbc for transfusion with C3d on alloantibody formation, and the effect on red cell alloantibody formation of modifying antigen presenting cells by blockage of the CD28-B7 co-stimulatory pathway with CTLA41g. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IN VIVO POTENTIAL OF HUMAN ES CELL-DERIVED BLOOD CELLS Principal Investigator & Institution: Kaufman, Dan S.; Assistant Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The isolation and characterization of human embryonic stem (ES) cells permits an exciting new approach to reach the goals of

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regenerative medicine. ES cells can be maintained virtually indefinitely as undifferentiated cells in culture, yet retain the ability to differentiate to form any cell type in the body. Therefore, human ES cells will provide an excellent source of cells to replace damaged or degenerated cells and tissues to treat a host of diseases. In the area of hematology, derivation of hematopoietic stem cells (HSCs) from human ES cells may be used for hematopoietic cell transplantation therapies for patients with hematologic malignancies such as leukemia or myeloma. Production of mature blood cells may provide an unlimited supply of red blood cells, platelets and other blood products from this well-defined source that is free of viral or other contaminants. Already, in vitro studies with human ES cells have produced hematopoietic, neural, cardiomyocyte, and other cell types. Hematopoietic cells of myeloid (white blood cells), erythroid (red blood cells), and megakaryocyte (platelet precursors) lineages can all be produced by coculture of human ES cells with irradiated bone marrow stromal cells. To reach their full potential, it is crucial to now demonstrate in vivo function of human ES cell-derived cells. This proposal aims to define the in vivo potential of hematopoietic cells derived from human ES cells by transplantation of undifferentiated human ES cells, and human ES cells induced to form hematopoietic precursors in vitro, into immunodeficient (NOD/SCID) mice. Use of this xenotransplant model to demonstrate human SCIDrepopulating cells (SRCs) is an effective measure of hematopoietic stem cells with longterm regenerative potential. Genetically modified (GFP-labeled) hematopoietic cells derived from human ES cells will also be used to demonstrate the stability of foreign gene expression, and the potential use of this model as a vector for gene replacement therapies. Serial transplantation experiments into secondary and tertiary hosts will be done to demonstrate the ability of HSCs derived from human ES cells to sustain longterm self-renewal. Since rhesus monkey ES cell are also available, successful completion of the aims of this proposal will lead to a non-human primate model of ES cell-derived hematopoietic cell transplantation. Eventually, clinical trials to define human ES cells as a novel source of cells for hematopoietic cell transplantation therapies will open new avenues to treat hematopoletic malignancies, immunodeficiencies, autoimmunity, and many other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERLEUKIN 13 STIMULATION OF HUMAN MONOCYTES Principal Investigator & Institution: Cathcart, Martha K.; Member; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 30-JUN-2003 Summary: Monocytes are a subset of white blood cells critical for normal immune function. They are important components of inflammatory responses and are believed to significantly contribute to atherosclerotic lesion pathology. In atherosclerotic lesions, monocyte/macrophages have been shown to express a lipid oxidizing enzyme, 15lipoxygenase (15-LO), that produces potent inflammatory mediators. Unique among the products of this enzyme are oxidized linoleate which we have shown to be the predominant oxidized fatty acid in atherosclerotic lesions. Normal monocytes do not express 15-LO, but are induced to do so by exposure to the cytokine IL-13 and expression of this enzyme is believed to correlate with disease progression in animal models of atherosclerosis. The studies proposed in this application will explore the IL-13 triggered signal transduction pathways in primary human monocytes and relate them to the downstream expression of 15-LO. Studies in Aim I will characterize the IL-13 receptor complex in human monocytes. Next, in Aim 2, the association and activation of Jaks with these receptor components will be assessed and activated Stats will be

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identified. The activation of Ser/Thr kinases will be evaluated (in Aim 3), expanding on our preliminary data that MAP kinases are activated by IL-13. The role of Jaks in this activation process will be investigated. Studies in Aim 4 will explore the role of Ser/Thr phosphorylation in regulating Jak/Stat phosphorylation and function. The biologic relevance of each of the activated pathways to the expression of 15-lipoxygenase and the related enhancement of monocyte-mediated LDL oxidation is the topic to be examined in studies described in Aim 5. In this final aim, additional investigations will be conducted to determine the role of the identified, IL-13 responsive pathways to general monocyte function with the goal.of identifying signaling pathways that are selectively involved in 15-LO expression but not required for other essential monocyte functions such as phagocytosis and superoxide anion production. The novelty of these studies is derived from the unique approaches to be employed to specifically dissect the roles of these pathways in intact human monocytes by virtue of the fact that monocytes are very conducive to antisense oligodeoxyribonucleotide manipulation of specific protein expression. These studies will substantially enhance our understanding of the signaling mechanisms induced upon exposure of monocytes to IL-13 and may suggest specific and selective means for modulating this response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: JUNCTION ADHESION MOLECULE CAR AND THE IMMUNE SYSTEM Principal Investigator & Institution: Carson, Steven D.; Pathology and Microbiology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 31-DEC-2007 Summary: (provided by applicant): CAR is a junction adhesion molecule (JAM), similar to other known JAM proteins. These proteins generally localize to tight junctions, where they participate in cell-cell adhesion and link to cytoplasmic proteins. Several JAM proteins bind counter-receptors on leukocytes and participate in their transmigration across cell layers. JAM interactions with most leukocyte types have been reported, except for B cells. New data show that CAR binds B cells, thus establishing that JAMleukocyte interactions include all major classes of white blood cells. New data also show that CAR binds immunoglobulins. Details of these new CAR activities remain to be elucidated. The long-term objective of this research is to identify the molecular interactions in which CAR participates and reach a more complete understanding of CAR function. In the sort-term, this project will identify the counter-receptor on B cells, cellular responses mediated by the CAR-B cell interaction, and the relationship of CARimmunoglobulin binding to CAR function. Specific Aim 1. Identify the CAR counterreceptor present on B cells. Obtain cDNA for expression and isolation of recombinant protein. The B cell counter-receptor will be purified from Raji cells and identified by comparison of amino-terminal sequence with protein and genetic databases, cDNA encoding the protein will be obtained from a repository (if the protein is known and the cDNA available) or by cloning de novo. Specific Aim 2. Characterize the response of B cells following CAR binding. In isolated peripheral blood mononuclear cells, B cells express early markers of activation following binding by CAR. Isolated B cells will be tested for responsiveness to CAR, and components essential for the response will identified. In addition, CAR may enhance B cell transmigration through endothelial cell layers. CAR's role in leukocyte migration will be studied using cells that express wild type and recombinant forms of CAR in a Transwell migration system. Specific Aim 3. Characterize the CAR-immunoglobulin interaction. Specific domains of CAR and immunoglobulins that mediate their interaction will be identified and mapped to

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determine their structural relationships to regions of these proteins known to participate in other interactions. Interactions between CAR binding immunoglobulins and the B cell counter receptor will identified. This work will advance knowledge of cells that form tight _junctions and their interactions with cells and molecules that must cross those barriers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LATENCY AND REACTIVATION TUBERCULOSIS Principal Investigator & Institution: Bishai, William R.; Associate Professor; International Health; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-APR-2007 Summary: (provided by applicant): Mycobacterium tuberculosis is remarkable in its ability to infect the human host and remain quiescent for many years only to reactivate when host defenses are suppressed. One-third of the global population is latently infected with tuberculosis, yet this clinically inactive state when bacilli are often noncultivatable is poorly understood and inadequately characterized. Appropriate animal models that more accurately mimic human diseases are needed to test vaccine candidates, and to understand the complex relationship between mycobacteria and host. The currently available animal models in mice and guinea pigs are characterized by multibacillary disease and are distinguished by the host response. Mice mount a poor delayed type hypersensitivity response and develop chronic lung disease, eventually succumbing to a progressive granulomatous pulmonary disease with high bacillary load. Guinea pigs also have a multibacillary disease, but are exquisitely susceptible with rapid hematogenous dissemination and a strong DTH response that results in rapid lung inflammation, destruction and death. Paucibacillary latent disease can only be induced with the administration of antibiotics. In contrast, rabbits are relatively resistant to aerosol infection with M. tuberculosis and mount a granulomatous response that effectively contains the bacilli. Over the course of 6-l2 months, all culturable bacilli disappear. In addition, the histopathologic response is remarkably similar to that of humans pointing to the rabbit model of tuberculosis as a promising avenue by which to study stage-specific changes in both host and bacilli. In this application, we will aerosol infect rabbits and allow the granulomatous lung lesions to regress to latency. With the use of immunosuppressive agents such as corticosteroids, iNOS inhibitors, and specific anti-cytokine antibody, we will reactivate infection. In parallel, we will refine the in vitro granuloma assay using rabbit white blood cells to have an in vitro model with which to correlate and compare our in vivo results. Harvesting serum and rabbit tissue at various stages of infection, we will characterize the stage-specific host humoral and cell-mediated immune responses. Understanding the antibody expression profile during latent disease may lead to important diagnostics in a disease hampered by diagnostics with low sensitivity and specificity. In addition, we will analyze the transcriptional bacterial response to various disease stages using microarrays and RT-PCR with molecular beacons. Finally, we will use a transposon mutant library to identify clones that are impaired in specific stages of infection. Appropriate animal models are critical to the successful development of tuberculosis vaccines, new drugs and better diagnostic tests for tuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANICAL PROPERTIES OF WHITE BLOOD CELLS Principal Investigator & Institution: Needham, David; Duke University Durham, Nc 27706

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Timing: Fiscal Year 2001 Summary: The major goal of these projects is to study the mechanisms of neutrophil motility. This is done by mechanically characterizing the three major components of cell motility: adhesion, cortical rearrangement and cell body contraction, and by characterizing the signaling of a variety of motility responses, such as pseudopod formation, locomotion, release of free cytosolic calcium, etc. The experimental techniques used are micropipet manipulation combined with video microscopy and also a new micropipet technique called the biointerface probe. This technique can be used to measure single molecular adhesive bond strengths, as well as to probe cell surface topography and cortical tension. During the past year, we have measured the cortical tension of the resting neutrophil and are continuing to perform these experiments upon stimulation by agents that are known to affect the stiffness of the sub-surface cortical layer, beginning with fMLP and cytochalasin D. We have also examined the effects of cytosolic calcium on the neutrophil motility response. Our plans are to continue these experiments and also to begin making measurements of adhesion molecule bond strengths, with emphasis on L-selectin. In this work, we use human neutrophils from venous blood as well as cells from finger pricks. These cells will be used for the entire duration of the grants. We expect to continue the experiments for approximately another five years. The total number of blood donors is expected to be in the range of 20 to 30, with 11 donors to date. This is not a multi-center project or a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF NEUROPATHOGENESIS IN BORNA DISEASE Principal Investigator & Institution: Hornig, Mady; Neurology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 30-JUN-2002 Summary: (Applicant's Abstract): Borna disease virus (BDV) is a newly classified RNA virus that infects the CNS of warm blooded animals to cause disturbances of movement and behavior. Natural infection has been confirmed only in horses, sheep, cattle, birds, and cats; however, primates can be infected experimentally. Although the data remain controversial, several investigators have reported evidence of infection in schizophrenia and affective disorders. Most previous work in BDV pathogenesis has focused on infected adult immunocompetent rodents and ungulates where dramatic disturbances in behavior, limbic circuitry, and monoamine neurotransmitter systems are reminiscent of aspects of some neuropsychiatric syndromes (autism, schizophrenia, or bipolar disorder). While these models are intriguing they are associated with CNS inflammation, marked loss of brain mass and gliosis and may be less relevant to neuropsychiatric diseases than those in neonatally infected rats where BDV induces subtle disturbances of behavior, and hippocampal and cerebellar dysgenesis without inflammatory cell infiltration. The broad objectives of this project will be to: (1) determine the mechanisms by which viral infections alter CNS architecture and function without invoking infiltrating inflammatory elements and (2) establish and investigate nonhuman primate models for BDV infection. Whereas models for persistent tolerant infection of neonatal rats have been described, nonhuman primate studies have been pursued only in acutely infected adult rhesus macaques. Studies proposed here will clarify whether primates can be infected in the perinatal period and, if so, whether the clinical, behavioral, and neuropathologic sequelae are consistent with human psychiatric disease. The investigators hypothesize that perinatal infections of Rhesus monkeys will manifest as subtle neurobehavioral and neuropathologic disturbances in a primate counterpart to the neonatal rat model of persistent BDV infection. They further

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propose that elucidation of the pathogenesis of such neurologic dysfunction through more extensive studies of neonatal BDV infection of rats will provide critical information about mechanisms of viral-CNS interactions that will then permit more focused, informed investigations in humans and nonhuman primates. Specific aims in the neonatal rat model are: i) characterize the nature of the behavioral, cognitive, and motor deficits; ii) examine the neuropathology associated with the neurologic abnormalities; iii) evaluate changes in levels of cytokines as potential mediators of BDVrelated damage; iv) discern whether apoptosis contributes to the neuropathology observed after neonatal infections and v) assess regional changes in neurotransmitter and neuroendocrine systems following neonatal BDV infection. The specific aims of the primate component of this application are to: 1) establish nonhuman primate models for BDV CNS infection using fetal and weanling Rhesus macaques; 2) determine the timecourse of the humoral immune response to BDV in infected fetal (intraventricular infection in utero) and weanling (intracerebral or intranasal infection) Rhesus macaques; 3) assess whether BDV nuclei acids can be detected in peripheral white blood cells (WBC) of infected Rhesus macaques; in the event that WBC are found to contain BDV nucleic acids can be detected in peripheral white blood cells (WBC) or infected Rhesus macaques; and in the event that WBC are found to contain BDV nucleic acids, to determine the distribution of BDV nucleic acids with respect to cell type and timecourse after infection; 4) define the hematologic, chemical, and virologic profile of cerebrospinal fluid (CFS) in infected fetal and weanling Rhesus macaques; 5) characterize the nature of any neurobehavioral, socioemotional, or motor deficits, and 6) evaluate neuropathology through in vivo (MRI and PET brain imaging) and postmortem analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINIATURE BLOOD CELL COUNTER FOR NEUROLOGICAL DISORDERS Principal Investigator & Institution: Lehdar, Raghu; Lehdar Systems Corporation 7721 E Gray Rd, Ste 204 Scottsdale, Az 85260 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 29-SEP-2002 Summary: (Applicant's abstract) Many clinical/medical conditions, i.e, neurological emergencies and disorders, require rapid intervention. Stroke is one example. In this context, availability of medical devices can enhance medical care to the patient. Blood cell counters, which are used to count blood components such as red and white blood cells, are ubiquitous in medicine as a diagnostic aid for disease identification or as a general tool for many medical therapies. The pre-eminent device in use today is the Coulter counter, which is expensive, large, and generally not portable, requiring at least a desktop, household current supply and a small support laboratory. The goal of this research and development project is to design a prototype miniature blood cell counter for home-care, or point-of-care analysis in doctors' offices, clinics, and hospitals. The novel blood counter we propose to develop is based on new, emerging micromachine technologies, and would be approximately the size of a small cell-phone, requiring very low electrical power. Similar to an inkjet print head, which is also a product of micromachined fluidics technology, the core analytical components of the miniature blood counter would be inexpensively mass-produced. The cost per unit would be low enough that the analytical portion could here placed after each use. PROPOSED COMMERCIAL APPLICATION: The proposed device has several likely economic advantages. Firstly, it will reduce the need for and cost of transport of blood samples to centralized laboratory. Secondly, expedient diagnosis will mean fewer clinical complications fewer office visits, shorter hospital stays and possible a reduced need to

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transport patients. It could result in an overall savings of several million dollars annually. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF RECEPTOR CYCLASE COUPLING Principal Investigator & Institution: Bourne, Henry R.; Cellular and Molecular Pharmacology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-1980; Project End 31-MAY-2004 Summary: The approximately 1 ,000 G protein-coupled receptors (GPCRs) of humans mediate key signals - triggered by photons, odorants, hormones, and neurotransmitters - in brain, heart, blood vessels, white blood cells, and virtually every organ and endocrine gland. The fact that most of these signals represent potential targets for drug therapy justifies the broad-based strategy of this proposal, which aims to understand the conserved molecular mechanisms responsible for transmitting G protein-mediated signals between signaling molecules, in vitro and in the context of the cell. The first two aims test relations between structure and function of the GPCR and the G protein trimer at the level of individual molecules. Experiments with GPCRs aim to: a. use molecular probes to determine how the extracellular surface of a GPCR actually binds the activating ligand; b. engineer metal binding sites that activate a GPCR by inducing coordinated movement of its transmembrane helices, allowing us to infer how the natural ligand induces similar movements; c. identify sites on the GPCR's intracellular surface that interact specifically with peptides representing different parts of the trimeric target. To understand the conformational changes in a G protein trimer that mediate its activation by the GPCR, a second set of experiments will: a. test the hypothesis that the GPCR uses the beta-gamma subunit of the G protein trimer as a lever to open a route for bound GDP to exit from its binding pocket in the alpha subunit and thereby activate the trimer; b. determine how key structural elements of the G protein alpha subunit cooperate during the activation process, by constructing metal binding sites that restrict movements of these elements, relative to one another. The third set of experiments uses fluorescent probes and fluorescence energy transfer (FRET) to determine the locations of G protein alpha and beta-gamma subunits in intact cells and ask how hormonal activation affects their interaction. Biochemical experiments with pure G protein subunits indicate that activation in the test tube causes the alpha subunit to dissociate from the beta-gamma heterodimer; it is not known, however, whether such a dissociation accompanies activation in an intact cell responding to a hormone. Investigation of this question begins by constructing functioning G protein alpha and beta-gamma subunits attached to fluorescent tags; the fluorescent subunits are used to assess their subcellular distributions in intact cultured cells, and FRET between coexpressed tagged beta-gamma and alpha subunits will reveal whether hormones cause them to dissociate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MULTICENTER TRIAL OF REPEATED DOSE OF LJP 394 IN PATIENTS WITH SLE Principal Investigator & Institution: Petri, Michelle; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001

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Summary: In systemic lupus erythematosus (SLE), certain white blood cells called lymphocytes make substances that cause inflammation in the body's own tissues. These substances are called anti-dsDNA antibodies (anti- dsDNA), and they have been shown to be associated with SLE kidney disease. The investigational drug to be tested in this clinical trial is called LJP 394. This drug is designed to attach to anti-dsDNA antibodies and remove them from the circulation. The drug will also attach to antibodies on certain white blood cells involved in causing immune diseases, including SLE. When given to a type of mouse that has lupus, LJP 394 reduced the numbers of anti-dsDNA antibodies in the blood and markedly decreased the severity of the kidney disease. When LJP 394 was given to lupus patients in earlier studies, anti-dsDNA antibodies were decreased. The purpose of this clinical research trial is to evaluate the ability of the experimental drug to lower the amount of anti-dsDNA antibodies in the blood, to help prevent damage to the kidneys by the anti-dsDNA antibodies, and to decrease the amount of other drugs required to control the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYELOPEROXIDASE ACTIVATION OF N ACETYLBENZIDINE Principal Investigator & Institution: Lakshmi, v; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: In workers exposed to benzidine, N'-(3'-monophospho-deoxyguanosin-8 -yl)N-acetylbenzidine (1A) was detected in exfoliated bladder cells and peripheral white blood cells. Because both cell types exhibit substantial peroxidatic activity, this was considered a likely mechanism for activation of N-acetylbenzidine (ABZ). For this reason, myeloperoxidase (MPO) metabolism of 3H-ABZ (0.06 mM) was assessed with analysis by HPLC. Substantial metabolism of ABZ by MPO was observed with a 2-fold increase elicited by inclusion of 100 mM NaCl in the reaction mixture. Taurine (10 mM) reduced metabolism in the presence, but not the absence of NaCl. Azide (1 mM), cyanide (10 mM), and ascorbic acid (1 mM) dramatically inhibited metabolism. With glutathione (0.1 mM), a new metabolite was observed which was sensitive to (-glutamyl transpeptidase and hydrolyzed to ABZ with mild acid or base treatment (0.1 N HCl or 0.1 N NaOH for 10 min). In the presence of dGp, MPO or 0.3 mM NaOC l produced an adduct whose formation was prevented by the presence of either glutathione or vitamin C. ESI/MS/MS analysis demonstrated this adduct to be 1A. Thus, ABZ is a reducing cosubstrate for MPO and a reductant for OCl-. MPO may be responsible for the activation of ABZ by peripheral white blood cells to form 1A. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURONAL INJURY AND BLOOD GENOMICS Principal Investigator & Institution: Sharp, Frank R.; Professor and Vice-Chairman; Neurology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (Adapted from applicant?s abstract): It is hypothesized that the white blood cell genomic response can be used to deduce the presence of neuronal injury due to acute neurological diseases, and that the blood genomic response patterns can be used to differentiate between the diseases causing the neuronal injury. Our preliminary data using microarray technology show unique patterns of gene expression by lymphocytes of adult rats subjected to ischemic strokes, hemorrhagic strokes, status epilepticus, hypoxia, hypoglycemia and sham-surgeries as compared to untouched controls. The

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first Aim of this proposal will determine whether short durations of global cerebral ischemia, focal cerebral ischemia (transient ischemic attack), hypoglycemia and seizures produce different white blood cell genomic responses in rats that can be used to differentiate between these conditions hours to days later. The second Aim will determine whether long durations of global ischemia, hypoglycemia and status epilepticus regulate specific genes in white blood cells in response to the diffuse neuronal injury caused by all of these conditions, and whether these genes can serve as indicators of the diffuse neuronal injury. The genomic expression of neutrophils, lymphocytes and whole blood will be examined at various times after cerebral ischemia, insulin-induced hypoglycemia, seizures and status epilepticus. Genes regulated in the different white blood cells by these conditions will be correlated with the presence of diffuse neuronal cell death in brain using TUNEL staining. The third set of Aims will determine whether the same genes regulated in white blood cells of rodents following single seizures and status epilepticus are also regulated in the white blood cells of men and women patients following seizures and status epilepticus. These studies will also determine whether blood genomic responses can be used to distinguish whether patients have had seizures, pseudoseizures or syncope, and whether some of the neuronal injury-related genes regulated in the blood of rodents with status epilepticus are regulated in patients with status epilepticus. Genes regulated more than two fold on microarrays will be confirmed by quantitative RT-PCR for all of the aims. The goal is to objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to days after they occur; and to begin to identify blood genomic markers of neuronal death associated with acute neurological diseases that might also be useful in chronic neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NORMAL DONOR BONE MARROW /PERIPHERAL BLOOD FOR LABORATORY RESEARCH Principal Investigator & Institution: Miller, Jeffrey S.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: Blood production takes place in the bone marrow cavity. Stem cells found in the bone marrow have the capacity to give rise to all blood cells including platelets, red blood cells, and white blood cells. We are interested in several different topics of stem cell biology. Some of the interest is in how cells grow, and how they differentiate to the different mature lineages. We are also interested in whether or not we can get genes into stem cells without their terminal differentiation. There are several different lines of investigation supported by NIH funded grants which require the use of normal bone marrow from paid donors. There are also some occasions when it is necessary to collect peripheral blood from these same donors. We have been collecting blood and normal bone marrow from donors for the past 6-8 years. The procedure is quite simple and performed by either one of the investigators on this protocol or a physician fellow in his or her laboratory. The procedure involves numbering up the skin over the posterior iliac crest and bone marrow aspiration under sterile technique. There is no special equipment which needs to be provided by the GCRC for this procedure other than availability of betadine, alcohol, sterile gloves and personnel to take vital signs and be there in case any problems result. It is estimated that a bone marrow aspiration from a normal donor takes about 15 minutes to perform and by the time a normal donor is checked in and is able to leave clinical area, approximately 30 minutes are scheduled per donor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROCESSING

PARALLEL

AND

HIGH

THROUGHPUT

41

MICROSAMPLE

Principal Investigator & Institution: Wilding, Peter; Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-JAN-1999; Project End 31-DEC-2002 Summary: Our goal is to design and fabricate an automated sample processor for massively parallel analysis of nucleic acid isolated from blood or bone marrow. It will comprise an array of miniaturized integrated disposable sample preparation devices designed for cell isolation and amplification of DNA or RNA. This processor will provide much needed simplification and automation of sample preparation essential for large-scale cancer studies, and will be part of a larger system containing an array of analytical stems fed by the individual sample preparation devices. Each device will accept a nucleic acid, either directly or after an intermediate amplification step (PCR, RT-PCR) to the detection modules. The complexity of the processing leads up to design the devices in two ways. Firstly, we will stack the individual preparative microstructures into a series of modules that interlock for fluidic connection. Modules can then be assembled for a desired preparative function. In a second and more challenging format, we will integrate all of the preparative functions into a single disposable totally integrated microchip. The microchip modules and the totally integrated microchip will be fabricated from silicon and glass using standard photolithography, wet-chemical etching and anodic bonding, and will contain microfilters, channels and chambers designed for each of the specific functions. Each type of device will contain microfilters, channels and chambers designed for each of the specific functions. Each type of device will be housed in a plastic module that will provide microfluidic connections in and out of the chip for sample application and delivery of processed nucleic acid. A key part of the microfluidics for each the proposed devices, is a new type of membrane valve based on a discontinuous microchannel and a membrane. The microstructured integrated devices will facilitate high throughput, fully automated parallel processing or samples for nucleic acid analysis with reduced sample and reagent consumption, and no cross-contamination. We have selected the liquid cancers as an important and clinically relevant model for assessing the effectiveness of the micro-chip based systems. The system will be optimized for both whole blood and bone marrow samples. The overall goal of this project will be accomplished by the design and optimization of: 1) a microfluidic module for sample application and delivery of processed sample for analysis; 2) a series of six microchips that will isolate human white blood cells, isolate cell sub-sets, isolate DNA or RNA, amplify DNA or RNA; 3) a totally integrated miniature microchip or a series of interlocking microchip modules that can perform combinations of cell isolation, cell selection, nucleic acid isolation and nucleic acid amplification; and finally, 4) system integration to provide a multi-place sample processor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHWAYS BIOMOLECULES

FOR

THE

INFLAMMATORY

DAMAGE

OF

Principal Investigator & Institution: Heinecke, Jay W.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-AUG-2002 Summary: (provided by applicant): Oxidants generated by activated white blood cells are critical to host defenses against microorganisms. However, overproduction of

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White Blood Cells

reactive species can damage host tissue. Indeed, white blood cells represent the cellular hallmark of inflammation, and oxidants have been implicated in tissue injury in inflammatory diseases ranging from atherosclerosis to neurodegenerative disorders to cancer.We have investigated four phagocyte-dependent pathways that oxidatively damage proteins in vitro. The pathways and their characteristic products are: myeloperoxidase and 3-chlorotyrosine; tyrosyl radical and o,o-dityrosine; hydroxyl radical and ortho-tyrosine; and reactive nitrogen species and 3-nitrotyrosine.Using two clinically relevant models of inflammation, we will study genetically engineered mice whose phagocytes are unable to produce specific oxidants. In the proposed research, we will ask three related questions. First, we will identify the pathways that generate chlorotyrosine, dityrosine, ortho-tyrosine, and nitrotyrosine in viva. The experiments will reveal whether a genetic deficiency of any of these oxidant-generating systems inhibits production of any of the chemical markers, thereby determining which pathway generates a particular marker in viva.Second, we will determine whether tissue, plasma, and urinary levels of the oxidized amino acids change in parallel. We will also investigate the absorption, metabolism, and urinary excretion of the oxidized amino acids. These experiments will determine whether plasma and urinary levels of these well-characterized products can be used as noninvasive markers of oxidative stress.Third, we plan to determine whether two proposed antioxidants-vitamin C or vitamin E- inhibit oxidative stress in our models of inflammation. Collectively, the proposed experiments will identify the oxidative pathways that cause phagocytes to damage tissues and will test the hypothesis that levels of oxidized amino acids in urine and plasma indicate levels of oxidative stress in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHAGOCYTOSIS--PULMONARY ALVEOLAR MACROPHAGES Principal Investigator & Institution: Stossel, Thomas P.; Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JUN-1979; Project End 30-JUN-2004 Summary: Cell crawling behavior is essential for human development, maintenance and defense, and instrumental in disease processes such as inflammation and the spread of cancer cells. This proposal addresses the machinery used by human white blood cells, tissue defense cells, tumor cells and blood platelets to crawl and change shape respectively. It focusses on two general questions based on key cell protein components which control how the major cell protein, actin, forms struts and levers that control cell shape and movements. These actin-regulating components were isolated originally from lung defense cells, the alveolar macrophages, and are believed important for lung protection and disease. The characterization of these proteins led to principles believed to explain how actin architecture, the so-called actin cytoskeleton, is maintained in the cell and how this architecture is changed to accommodate crawling movements. The current proposal sets out to explain how one of the components, a protein called filamin-1 , causes actin filaments to take on particular configurations within the cell and how signaling processes that mediate instructions delivered from outside cells to elicit crawling behavior might regulate filamin-l's functions, which also include linking the actin cytoskeleton to plasma membrane receptors and serving as a scaffold for cellular trafficking and signaling reactions. The proposal also plans to examine how human blood neutrophils, the most rapidly crawling of our cells, determine where and when to assemble new actin filaments, based on hypotheses derived from a systematic study of the second component, a protein named gelsolin. The investigations involve elucidation of how signal intermediates such as GTPases and phospholipids work to promote actin

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polymerization. The eventual goal is to understand these processes sufficiently to modify them in hopes of mollifying inflammation and metastatic tumor spread. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACODYNAMIC MONITORING OF MYCOPHENOLATE MOFETIL TREATMENT Principal Investigator & Institution: Morris, Randall E.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: In order to obtain more knowledge on the mechanism of action of mycophenolate mofetil (MMF), a drug used in the prevention of acute rejection after kidney and heart transplantation, we studied the effects of this drug in healthy volunteers. Ten healthy volunteers were treated with a single dose of 1 gram of mycophenolate mofetil (MMF). Just before treatment and 1, 2, 6, 12 and 24 hours after administration of the drug blood was drawn to study its effect on the proliferation and the activation of the white blood cells that cause rejection (lymphocytes) and on the production of certain activation hormones (cytokines). The magnitude of inhibition of these lymphocyte functions were compared with the concentrations of MMF measured in blood of the human volunteers at the same time points. We observed that there was a strong correlation between the amount of MMF present on one hand and the inhibition of proliferation and activation on the other hand. The effect on cytokine production was only modest, and not correlated with drug concentrations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHASE IIA TO EVALUATE LUNG BIOEFFICACY OF DMP777 IN ADULTS W/ CYSTIC FIBROSIS Principal Investigator & Institution: Moss, Richard B.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: This study is an open-label, multiple dose, dose-escalation protocol to evaluate the safety and preliminary efficacy of an orally administered drug, DMP777, which reduces the inflammation in the lungs caused by excessive activity of white blood cells called neutrophils. The excessive inflammatory activity is due to a chemical called elastase; DMP777 blocks this activity, and is thus an anti-inflammatory drug. In this protocol, patients with cystic fibrosis are evaluated for the presence of the drug in lung fluids by obtaining samples of lung fluids using a technique called bronchoalveolar lavage, these fluids are also assessed for levels of inflammatory cells and chemicals at baseline and after receiving the drug. The body's handling of metabolism of DMP777 is assessed by measures of lung and blood levels after multiple doses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PLATELET LEUKOCYTE PHYSIOLOGY IN CARDIOPULMONARY BYPASS Principal Investigator & Institution: Smith, Brian Richard.; Professor; Laboratory Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-AUG-1991; Project End 30-JUN-2002 Summary: (Adapted from the investigator's abstract) Cardiopulmonary bypass profoundly alters the interacting coagulation and immune systems, resulting in

44

White Blood Cells

seemingly contradictory coagulopathic, prothrombotic, immunosuppressive and proinflammatory diatheses that are responsible for cardiopulmonary bypass related pulmonary and myocardial injury and bleeding early during bypass and hypercoagulability and immunologic disturbances later in cardiopulmonary bypass. As demonstrated previously under this grant, cardiopulmonary bypass results in a dynamic alteration in platelet-leukocyte-erythrocyte-endothelial adhesive and functional interactions, in part initiated by terminal membrane component generation. Using in-vivo studies and in-vitro whole blood model and a simulated extracorporeal circulation model, the PI has shown that antigenic and functional upregulation of specific beta2 integrins occurs on circulating phagocytes in cardiopulmonary bypass, platelet alpha-granule release and P-selectin expression occurs with formation of circulating platelet -leukocyte conjugates during cardiopulmonary bypass at anticomplement C5 monoclonal antibody blocks both platelet and neutrophil activation during simulated extracorporeal circulation. Further work suggests that damaged and reticulated red blood cells promote activated platelet microparticle formation, that platelet activation may be a result of C5b-9 while adhesion molecule upregulation occurs a consequence of C5a activity. Furthermore, neutrophil granule release and adhesion upregulation are separable events and reticulated platelets represent a platelet subset which shows differential functional activity and may by preferentially lost during cardiopulmonary bypass. The aims of this application are to 1) define which complement components and other mediators initiate which parameters of platelet white blood cell endothelial activation 2) to define the molecular basis of erythrocyteplatelet-white blood cells interactions which generate cellular and soluble mediators of coagulation and inflammation in cardiopulmonary bypass and to define alterations in endothelial cells inducted by simulated extracorporeal circulation using an addition to the current model. The long term goals of these studies is to develop therapeutic strategies to alleviate complications of extracorporeal circulation and to understand the basic biology of platelet-white blood cell-erthyrocyte-endothelial interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEINASE INHIBITORY MECHANISMS OF SERPINS Principal Investigator & Institution: Salvesen, Guy S.; Professor; Burnham Institute 10901 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 30-JUN-2004 Summary: (adapted from applicant's abstract): Proteolysis plays a role in almost every developmental pathway and normal function of the human organism. Quite often, several related proteases cooperate to drive proteolytic pathways that converge on a significant biologic event, often-used examples being blood coagulation, fibrinolysis, antigen presentation, and apoptosis. The balance of proteolysis is achieved by the presence of specific protease inhibitors. Predominant in this are the serpins, members of an evolutionary related superfamily that are demonstrably responsible for regulating the extracellular pathways of coagulation, fibrinolysis, and complement fixation, and one could call these the "regulating" serpins. Related to these are serpins that block adventitious proteolysis due to the release of potentially damaging proteases from white blood cells. One can call these the "emergency" serpins since they are thought to block specific proteases, rather than allowing proteolysis to proceed at a regulated rate. Though there is a great deal known about the regulating and emergency plasma serpins, their mechanism of action is still unknown. Moreover, a more recently recognized group of at least 8 human serpins, functioning inside cells, has appeared in the literature. The function of only three of these is known. This leads to the hypothesis that the existence

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of a group of protease-inhibitory serpins with unknown targets points to as yet unidentified fundamental proteolytic processes occurring inside cells. The aims of this proposal are to examine aspects of the inhibitory mechanism of serpins by biochemical and X-ray crystallographic methods, and to use this knowledge to determine the cellular targets of a subset of the recently identified intracellular serpins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMIC AND MRNA PROFILING OF URINE AND URINE SEDIMENT Principal Investigator & Institution: Rovin, Brad H.; Professor; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The objective of this project is to validate urine protein and gene expression profiling as tools to derive novel mechanistic and diagnostic information from the urine of patients with glomerulonephritis. Although previous investigations have examined urine to gain insight into the pathogenesis of renal disease, and to identify clinically relevant markers of disease activity, severity, or prognosis, such studies were limited to analysis of a relatively small number of prechosen candidate proteins. It is postulated that by examining the entire urinary proteome during glomerulonephritis, as well as the proteins and genes expressed by leukocytes present in nephritic urine, previously unrecognized patterns of protein expression will emerge. Investigation of these protein networks will lead to new insights into the pathogenesis of glomerular disease. Furthermore, by characterizing patterns of protein expression associated with distinct phases of disease activity, novel prognostic indicators will be identified. These themes will be developed in two Specific Aims. In Aim 1, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) will be used to map the urine proteins of a well-characterized cohort of patients with SLE nephritis before, during, and after relapse of renal disease. These studies will define how the urinary proteome changes from inactive disease through active SLE. Differentially expressed proteins from these different phases of disease activity will be further identified by mass spectrometry (MS). It is predicted that the protein networks engaged before relapse will reflect mechanisms of disease activation, while proteins expressed in active disease will represent mediators of renal injury, and proteins expressed during treatment will determine therapeutic success or failure. Aim 2 will extend proteomics to the leukocytes present in the urine of patients with active SLE nephritis. Additionally, cDNA microarray analysis will be used to characterize genes expressed by these white blood cells. Urinary gene and protein expression will be compared to that of simultaneously obtained peripheral blood mononuclear cells. It is anticipated that differentially expressed proteins and genes will reflect intra-renal inflammatory events. The results of this project are expected to demonstrate the relevance of urinary proteomic and cDNA microarray analyses by identifying previously unrecognized protein networks active in SLE nephritis that challenge existing paradigms of renal disease pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PS-341 IN HEPATOCELLULAR CARCINOMA: A PHASE II TRIAL Principal Investigator & Institution: Berlin, Jordan D.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2005

46

White Blood Cells

Summary: (provided by applicant): Hepatocellular carcinoma, a common malignancy worldwide, now with apparently increasing incidence in the United States, remains a deadly disease with few, if any, treatment options for unresectable disease. Activation of a key regulatory protein, nuclear factor kappaB (NF-kappaB) appears to be important in the development, growth and spread of hepatocellular carcinoma. PS-341, a proteasome 26S inhibitor, is being studied as an anticancer agent. By inhibiting proteasome 26S, PS 341 prevents the ubiquitination and degradation of IkappaBalpha, which remains bound to NF-?B, preventing activation of NF-?B. However, proteasome 26S interacts with several cellular proteins that play a role in malignancy, including p21, p27, p53, Bax and Bcl-2. NF-kappaB increases expression of chemokines/cytokines (e.g. MIP1-alpha, GROalpha, IL-8, and IL-1), and on growth factors such as vascular endothelial growth factor (VEGF). This proposal is designed first to learn the clinical effects (toxicity and efficacy) of PS-341 when administered in a phase II trial to patients with hepatocellular carcinoma. In addition, white blood cells and patient sera will be tested for effects of PS 341 on phosphorylation of IkappaBalpha, nuclear localization of NF-kappaB, apoptosis, and effects on chemokines and growth factors in serum. These will be correlated with clinical parameters (efficacy and toxicity) as well as effects in tumor tissue. Tumor tissue will be analyzed for PS 341 effects on phosphorylation of I(B(, nuclear localization of NF-kappaB, apoptosis, and other key regulatory proteins, p21, p27, p53, Bax, and Bcl-2. The goal of these laboratory evaluations is to determine first, if PS 341 appears to be affecting its anticipated target in tumor cells, and second, if any of the serum or WBC parameters appear to be potential markers of biologic activity worthy of further study on larger trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REACTIVE SCAR-FORMING ASTROCYTES AFTER SPINAL CORD INJUR Principal Investigator & Institution: Sofroniew, Michael V.; Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 30-JUN-2004 Summary: (provided by applicant): Astrocytes respond to spinal cord injury (SCI) by altered gene expression, hypertrophy and proliferation, a process known as reactive astrocytosis. Considerable descriptive information is available about molecules produced by reactive astrocytes, but the functions of these cells are not well understood. Astrocyte scars are thought to prevent axon regeneration after SCL but evidence also points towards important potential roles for reactive astrocytes in the process of acute local tissue repair. We have developed an experimental model to demonstrate specific functions of reactive astrocytes by targeting the specific ablation of this cell type after CNS injury in transgenic mice. Using these mice we have shown that after injury in the forebrain, reactive astrocytes are essential for protection of local neurons, repair of the blood brain barrier and restricting the infiltration of inflammatory white blood cells. In addition, we found increased local sprouting of axons in areas where reactive astrocytes were ablated. In this proposal we will apply this transgenic model to study the roles of reactive astrocytes in SCI. First, we will ablate reactive scar-forming astrocytes at the site of a small, acute spinal cord lesion to characterize the roles played by these cells in (i) the acute injury response and repair process after SCI, and (ii) long term effects on nerve fiber tract integrity and capacity for regrowth. These findings will tell us whether reactive, scar-forming astrocytes are, as we predict, essential for acute tissue repair after SCI, such that their absence or dysfunction will markedly exacerbate the tissue

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47

degeneration and detrimental effects associated with small spinal cord lesions. Next, we will determine the extent of axon survival and capacity for local and long distance axon regeneration in the transected dorsal columns of the spinal cord, after transgenicallytargeted ablation of reactive scar-forming astrocytes, alone or in combination with grafts of immature astrocytes, neural stem cells or olfactory ensheathing cells. These findings will tell us whether ablation and appropriate replacement of reactive, scar-forming astrocytes can, as we predict, lead to substantially improved regrowth of transected long tract axons after acute SCI. Together, information from these studies will provide essential ground work for future dissection of the underlying molecular signaling mechanisms that mediate specifically identified roles (both beneficial and detrimental) of reactive astrocytes after SCI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF B CELL DEVELOPMENT BY NEUROPEPTIDES Principal Investigator & Institution: Mcgillis, Joseph P.; Associate Professor; Microbiology Immunology, and Molecular Genetics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: The objective of this project is to understand how the nervous system influences the production of new B cells in the bone marrow. B cells produce antibodies following vaccination or exposure to a pathogen. The function of the immune system requires that new white blood cells (leukocytes), including B cells, be produced at controlled rates. Under or overproduction of leukocytes could lead to a reduced capacity to fight infectious disease or to leukemia, autoimmunity or other disease states. For this reason it is critical that the rate of production of leukoctyes is maintained at levels that insure sufficient numbers for their proscribed protective functions without risk of overproduction. The focus of this project is on the role of the neuropeptide calcitonin- gene related peptide (CGRP) in regulating early B cell differentiation. Cells in the immune system have CGRP receptors and CGRP influences the activity of mature lymphocytes, macrophages and granulocytes. CGRP and another sensory neuropeptide, substance P, play a role in regulating the differentiation of distinct leukocyte populations. CGRP is found in nerve endings in bone marrow, hematopoietic cells have CGRP receptors, CGRP induces production of B cell regulatory cytokines and inhibits B cell progenitor responses to IL-7. The specific aims of this project are to show that administration of CGRP reduces the number of B cell progenitors, to identify CGRP receptor expressing cells in the B cell lineage, to examine how specific stages in early B cell development are influenced by CGRP, and to study the cellular mechanisms by which CGRP blocks B cell differentiation. The in vivo studies will determine the number of pre-B CFUs following CGRP treatment. CGRP receptor expressing cell populations will be identified by CGRP receptor mRNA analysis and by functional responses to CGRP. The role of CGRP in B cell differentiation will be studied using short term in vitro studies with cells derived from bone marrow. These studies will examine the effect of CGRP on proliferation and differentiation of distinct populations of B cell precursors present in bone marrow. Preliminary studies suggest that CGRP inhibits early B cell differentiation by cellular mechanisms involving events influenced by IL-7 and by activation of NFkappa-B. Studies will determine how CGRP inhibits NFkappa-B activation in a pre-B cell line and will examine how CGRP inhibits IL-7 responses in normal B cell progenitors. A better understanding of CGRP's role in B cell development may offer new avenues for new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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White Blood Cells

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Project Title: ROLE OF T TYPE CYCLINS IN T CELL ACTIVATION Principal Investigator & Institution: Grana, Xavier; Associate Professor; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2001 Summary: The purpose of this study is to understand mechanisms of the activation of T cells, an essential cellular component of the immune system. Peripheral blood lymphocytes (white blood cells) will be isolated from the blood and used in experiments designed to understand the mechanism of lymphocyte activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES IN PORPHYRIA CUTANEA TARDA Principal Investigator & Institution: Anderson, Karl E.; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001 Summary: Porphyria cutanea tarda (PCT) is the most common of the porphyrias and is due to a marked deficiency of uroporphyrinogen decarboxylase in liver. The uroporphyrinogen decarboxylase deficiency found in PCT is primarily acquired. The aims of this study are as follows. 1. Vitamin C status is assessed before and after standard treatment (either repeated phlebotomy or low-dose choloroquine) by measuring vitamin C levels in serum and white blood cells. This will test the hypothesis that vitamin C is an antioxidant in the liver and that its deficiency may contribute to activation of PCT. 2. Activity of CYP 1A2 is assessed in vivo using 13C-caffeine and 13Cmethacetin breath tests and also by measuring the clearance rate of caffeine from blood and urinary excretion of caffeine metabolites. 3. The role of hepatitis C infection is assessed by (a) observing the effect of treatment of PCT by repeated phlebotomy or lowdose chloroquine on abnormalities in liver function tests and on the presence of hepatitis C antibody and hepatitis C RNA in plasma; and (b) by observing the frequency of recurrence of PCT in patients who are treated with interferon x-2b as compared to patients who are not treated with this drug. Standard serum chemistries as well as a [13C]phenylaline breath test are used to assess liver function. The indications for treatment with interferon x-2b will be the standard indications for use of this drug in patients with hepatitis C and will not be influenced or specified by this protocol. Patients are treated first for PCT, because treatment for PCT is almost always successful, whereas treatment for hepatitis C is usually not. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TELOMERES AND VASCULAR AGING Principal Investigator & Institution: Aviv, Abraham; Professor; Hypertension Research Center; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: The use of chronological age in clinical practice and in aging research is based on the premise that biological aging proceeds at an identical pace for all human beings. Such an approach overlooks the pnncipals of biological diversity. The central hypothesis of this project is that telomere length, as expressed in white blood cells, provides an account additional to chronological age, of variation in vascular aging among human beings. This hypothesis will be tested in the Offspring Study cohort of the Framingham Heart Study. The project will also seek through genome-wide search for genetic regions with large effects on telomere length. The specific aims of this project

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are: 1. To examine the relations between telomere length and indices of arterial aging in the previously phenotyped/genotyped Offspring Study cohort of the Framingham Heart Study. The indices of arterial aging include: brachial pulse pressure, central pulse pressure, augmentation index, and carotid-femoral, carotid-radial and carotid-brachial pulse wave velocities; 2. To assess heritability of telomere length and identify genetic loci that explain variation in telomere length. Results would lead to a better understanding of the heterogeneity of vascular aging, test the concept that telomere length may serve as an index of biological aging, and provide information on genetic determinants of telomere length in human beings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PATHOPHYSIOLOGY OF INTRA-AMNIOTIC INFECTION Principal Investigator & Institution: Calhoun, Darlene A.; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001 Summary: The purpose of this research is to determine the amount of granulocyte colony-stimulating factor (G-CSF) in the blood. G-CSF stimulates the growth of white blood cells which help the body fight infection. Two groups of pregnant women will be studied. The first group of women will have chorioamnionitis and the second group will be the normal control group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE REGULATION OF THE G-PROTEIN, GALPHAI2 BY UNC5H2. Principal Investigator & Institution: Komatsuzaki, Katsumi; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 08-JAN-2003 Summary: (provided by applicant): The overall goal of this proposal is to understand the characteristics of Gia2-UNC5H2 interaction and define its role in events that are critical to lung development. Gia2 is expressed in the lung and is implicated in cell migration, proliferation and differentiation but also in more biologic processes such as organ development. Recently we identified an interaction between UNC5H2 and Gia2 in vitro and in vivo and showed UNC5H2 modulates Gia2 signaling. UNC5H2 is a regulator of neuronal axonal guidance molecule, which is also expressed in white blood cells and lung. Specific Aim I: To define the critical amino acids in Gia2 that are necessary for Gia2-UNC5H2 interaction and define the critical region of TJNC5H2 for this binding. Specific Aim II: To elucidate the site and time course of expression of UNC5H2 during growth and development of the lung in vitro and in vivo. Specific Aim III: Define the role of Gia2-UNC5H2 in the regulation of cell migration, cell growth and branching morphogenesis in lung culture. First, a basic understanding of the regulation of Gia2-UNC5H2 pathways is likely to provide insight into lung development as well as other organs. Second, the understanding of cell migration is particularly important for immune cell migration. Excess migration of these cells induces a broad array of lung diseases including interstitial lung disease, ARDS and bronchiectasis. These diseases are responsible for a large number of deaths in the United States. Thus understanding pathways that may down regulate cell migration may have significant implications for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE CARDIOMYOPATHY

OF

ADENOSINE

IN

CHRONIC

ISCHEMIC

Principal Investigator & Institution: Le, Dai-Trang Elizabeth.; Md; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The candidate received superb training in myocardial contrast echocardiography (MCE) and coronary physiology research in Dr. Sanjiv Kaul's experimental laboratory and is committed to the development of an academic career in cardiovascular medicine. The K08 grant would allow her to achieve her immediate career goals, which are to continue to develop expertise in the field of MCE as new ultrasound equipment and microbubbles are developed, to gain an understanding of the pathogenesis of chronic ischemic cardiomyopathy, to learn histopathologic, immunohistochemical, ELISA, EIA, RIA, and SPA techniques, and to become familiar with cardiac MRI as a research tool. Her long-term career goals include development into an independent investigator in the experimental laboratory in the subject of chronic LV dysfunction and MCE, participation in translational research protocols with a focus on chronic ischemia and therapeutics for ischemic congestive heart failure (CHF), and practicing clinical cardiology with an emphasis on coronary artery disease and echocardiography. In sum, she is committed to developing a successful academic career in cardiovascular medicine. CHF is a major health problem in industrialized countries and its prevalence, morbidity, and mortality are rapidly rising. The pathophysiology of ischemic CHF is not well understood. The overall aim of this research proposal is to investigate the role of adenosine in chronic ischemic cardiomyopathy in a canine model of ameroid-induced left ventricular (LV) dysfunction. An A1 allosteric enhancer, a selective A2A agonist and antagonist, and a selective A3 agonist will be given to study their effects on angiogenesis, apoptosis, inflammation, vasodilation, and cardioprotection. At baseline, maximal LV dysfunction, and 1 month, 3 months, and 6 months after administration of the adenosine agonist or antagonist, we will perform MCE to examine myocardial perfusion and angiogenesis, contrast echo imaging of inflammation, MRI to examine myocardial mass, LV volume, and regional and global LV function, microspheres injection to assess myocardial blood flow, and interstitial fluid collection from the myocardium to examine the presence of cytokines and white blood cells. After the 6-month evaluation, histopathology and immunohistochemistry will be performed to correlate functional changes with histologic evidence of inflammatory changes, apoptosis, and angiogenesis. The research environment involves close mentoring by Drs. Kaul and Siragy, use of their lab space, and enthusiastic support from the division chief and consultants, including Dr. Joel Linden who is an authority on the role of adenosine in cardiovascular physiology and pharmacology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TO EVALUATE SAFETY & EFFICACY OF ISIS 2303 IN STEROID DEPD CROHNS DISEASE Principal Investigator & Institution: Varilek, Gary W.; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001 Summary: This is a D protocol with IRB approval. The object is to study the safety and efficacy of ISIS 2302 in steroid-dependent Crohn's disease. ISIS 2302 is antiinflammatory, anti-sense therapy. This is based on its ability to bind to and inhibit

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synthesis of Intercellular Adhesion Molecule-1 (ICAM-1). ICAM-1 is a central molecule in the immune and subsequent inflammatory response involved in the movement of white blood cells from the blood to sites of inflammation. The study is aimed to evaluate whether ISIS 2302 could offer an alternative treatment to patients with Crohn's disease who are dependent on systemic steroids which have broad and serious side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOXICOLOGICAL POLYMORPHISM

RELEVANCE

OF

HUMAN

GST

PL-L

Principal Investigator & Institution: Singh, Shivendra V.; Professor/Program Leader; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 22-SEP-2002 Summary: (Adapted from the Investigator's Abstract)The overall objective of this project is to define the significance of human glutathione S-transferase _ (hGSTP1-1) polymorphism in cellular detoxication of carcinogenic diol epoxides (DEs) of polycyclic aromatic hydrocarbons, which are widespread environmental pollutants and believed to be etiological factors in human chemical carcinogenesis. Recent preliminary studies indicate that the two polymorphic forms of hGSTP1-1, which differ in their primary structure by a single amino acid in position 104, significantly differ in their activity toward DEs. These observations led the investigators to hypothesize that the hGSTP1-1 polymorphism may be an important determinant of variable response of individuals to PAH-induced cancer. This hypothesis will be tested by a series of experiments proposed under four interrelated specific aims. In specific aim 1, they will compare the kinetic parameters and catalytic efficiencies of three naturally occurring polymorphic forms of hGSTP1-1 [hGSTP1-1(I104,A113), hGSTP1-1 (V104,A113) and hGSTP1-1(V104,V113)] and hGSTP1-1(I104,V113) form, prepared by site-directed mutagenesis, in the GSH conjugation of various bay-region and fjord-region DEs. In specific aim 2, we will investigate the effects of overexpression of hGSTP1-1 variants, through stable transfection in HepG2 cells, on cytotoxicity of anti-BPDE and anti-CDE [ultimate carcinogenic metabolite of benzo(a)pyrene and chrysene, respectively] and on formation of2 the predominant DNA adduct of anti-BPDE (trans-N dG-BPD adduct). Studies in specific aim 3 are designed to determine the correlation between expression of hGSTP11 variants in humans (by PCR using blood samples from normal healthy subjects as well as cancer patients) and GST activity toward anti-BPDE,2 trans-N dG-BPD adduct formation (in white blood cells of same individuals) and susceptibility to cancer (medical history) of the blood donors. Finally, specific aim 4 is to elucidate the molecular mechanism of differences in the kinetic properties of hGSTP1-1 variants in the GSH conjugation of DEs by X-ray crystallography and molecular modeling of their active sites. These studies should enhance our understanding of the protective mechanisms against carcinogenic DEs and also shed light on the physiological significance of hGSTP1-1 polymorphism in the detoxication of this class of ultimate carcinogens. In the long term, the information generated from this project may be valuable in formulating strategies for cancer prevention in humans and may help in identifying human population at risk for PAH-induced cancer. The proposed studies will assess a total of 408 cases plus and an equal number of controls. The population will consist of members of both genders and will include Caucasians, blacks and other minorities, as available and representative of the patient base at Mercy Hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VISCOELASTICITY OF WHITE BLOOD CELLS Principal Investigator & Institution: Hochmuth, Robert M.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: The objective of our research for the past year is to characterize cytokinestimulated adhesion receptor kinetics that enable endothelial cells to capture and guide neutrophils to the site of inflammation. The transition from random interactions of freely-flowing leukocytes with the endothelium to specific adhesion and diapedesis is a well-ordered mechanism with intercellular adhesion coordinated by signaling. Eselectin, for example, is not constitutively expressed on microvascular endothelial cells (MVEC), but is induced in response to cytokine or endotoxin stimulation. E-selectin supports neutrophil rolling, a preliminary step in leukocyte transmigration. While the temporal patterns of adhesion molecule expression in large vessel endothelium have been well characterized, there are fewer studies of MVEC, which is more closely related to the post-capillary venules where neutrophils transmigrate. We show that there is correlation between structural characteristics of E-selectin expression and functional adhesion (FA) between E-selectin and anti-E-selectin mAb-coated beads. MVEC were stimulated with IL-1a while two separate assays of E-selectin expression kinetics were performed for 4-6 hours using either flow cytometry or the micropipette FA assay. In flow cytometry measurements, the number of E-selectin receptors expressed on HMVEC increased 20-fold following 6 hours of stimulation. In parallel micropipette FA assays between HMVEC and anti-E-selectin mAb-coated beads, FA increased 10-fold. While FA depends on receptor and ligand density, parameters measured using flow cytometry, it is also determined by physical characteristics of surface contact intrinsic to the adhesion assay and effective receptor/ligand forward reaction rates. Ultimately, we plan to replace the antibody-coated bead probe with a neutrophil and study the kinetics of specific EC receptor- neutrophil ligand interactions. We have completed the studies on the static and dynamic lengths of neutrophil microvilli and this work has been published in the Proceeding of National Academy of Science. Microvilli, with most of the L-selectin and PSGL-1 (P-selectin glycoprotein ligand-1) on their tips, are believed to promote the initial arrest of neutrophils on endothelium. At the rolling stage following arrest, the lifetimes of the involved molecular bonds depend upon the pulling force imposed by the shear stress of blood flow. With two different methods, electron microscopy (with the cells fixed by a non-shrinking procedure) and micropipette manipulation, we have obtained two comparable neutrophil microvillus lengths, both about 0.3 5m in average. We have found also that, under a pulling force, a microvillus can be extended (microvillus extension) or a long thin membrane cylinder can be formed from it (tether formation). If the force is less than or equal to 34 pN (1 3 pN), the length of the microvillus will be extended; if the force is larger than 61 pN (1 5 pN), a tether will be formed from the microvillus at a constant velocity, which depends linearly upon the force. When the force is between 34 pN and 61 pN (transition zone), the degree of association between membrane and cytoskeleton in individual microvilli will dictate whether microvillus extension or tether formation occurs. When a microvillus is extended, it acts like a spring with a spring constant of 43 pN/5m. In contrast to a rigid or non-extendible microvillus, both microvillus extension and tether formation can decrease the pulling force imposed on the adhesive bonds, hence prolonging the persistence of the bonds at high physiological shear stresses. SIGNIFICANCE: This research will advance understanding of how circulating neutrophils effect phagocytosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

A comparison of the NADPH oxidase in human sperm and white blood cells. Author(s): Armstrong JS, Bivalacqua TJ, Chamulitrat W, Sikka S, Hellstrom WJ. Source: International Journal of Andrology. 2002 August; 25(4): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121572&dopt=Abstract

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A link between the p53 germ line polymorphisms and white blood cells apoptosis in lung cancer patients. Author(s): Biros E, Kohut A, Biros I, Kalina I, Bogyiova E, Stubna J. Source: Lung Cancer (Amsterdam, Netherlands). 2002 March; 35(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844595&dopt=Abstract

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A modified immunochemical assay for the fast detection of DNA damage in human white blood cells. Author(s): Timmerman AJ, Mars-Groenendijk RH, van der Schans GP, Baan RA. Source: Mutation Research. 1995 June; 334(3): 347-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7753098&dopt=Abstract

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A monograph on hematology. Part II. Disorders of white blood cells. Author(s): Angelillo JC, Dolan EA, Peters CR, Georgiade NG. Source: N C Dent J. 1978 Summer-Autumn; 61(2-4): 27-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=290860&dopt=Abstract

3

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 group of glucocerebrosidase isozymes found in human white blood cells. Author(s): Ginns EI, Brady RO, Stowens DW, Furbish FS, Barranger JA. Source: Biochemical and Biophysical Research Communications. 1980 December 16; 97(3): 1103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7470138&dopt=Abstract

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A pilot study of detection of DNA adducts in white blood cells of roofers by 32Ppostlabelling. Author(s): Herbert R, Marcus M, Wolff MS, Perera FP, Andrews L, Godbold JH, Rivera M, Stefanidis M, Lu XQ, Landrigan PJ, et al. Source: Iarc Sci Publ. 1990; (104): 205-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2228118&dopt=Abstract

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A simple flow-cytometric method for absolute counting of residual white blood cells in leukocyte-reduced packed red cells. Author(s): Gomez-Arbones X, Pinacho A, Ortiz P, Macia J, Gallart M, Araguas C, Sanchez JM, Teixido M. Source: Vox Sanguinis. 1999; 76(1): 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9933857&dopt=Abstract

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Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg. Author(s): Nash GB, Thomas PR, Dormandy JA. Source: British Medical Journal (Clinical Research Ed.). 1988 June 18; 296(6638): 1699701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3135883&dopt=Abstract

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Active recovery reduces the decrease in circulating white blood cells after exercise. Author(s): Wigernaes I, Hostmark AT, Kierulf P, Stromme SB. Source: International Journal of Sports Medicine. 2000 November; 21(8): 608-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156284&dopt=Abstract

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Adherence of cells to myelin basic protein. I. Adherence of red and white blood cells from patients with multiple sclerosis to myelin basic protein. Author(s): Najbauer J, Kosaras B, Tigyi GJ. Source: Acta Neurologica Scandinavica. 1987 September; 76(3): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2446461&dopt=Abstract

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Adrenoleukodystrophy: evidence for cytoplasmic inclusions in white blood cells. Author(s): Chemke J, Livni N, Rosenmann E. Source: Pediatr Pathol. 1986; 6(2-3): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3029738&dopt=Abstract

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Adrenoleukodystrophy: impaired oxidation of very long chain fatty acids in white blood cells, cultured skin fibroblasts, and amniocytes. Author(s): Singh I, Moser AE, Moser HW, Kishimoto Y. Source: Pediatric Research. 1984 March; 18(3): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6728562&dopt=Abstract

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Airborne levels of polycyclic aromatic hydrocarbons: 32P-postlabeling DNA adducts and micronuclei in white blood cells from traffic police workers and urban residents. Author(s): Merlo F, Bolognesi C, Peluso M, Valerio F, Abbondandolo A, Puntoni R. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1997; 16(2-3): 15762. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9275996&dopt=Abstract

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Alpha glucosidases in white blood cells, with reference to the detection of acid alpha 1-4 glucosidase deficiency. Author(s): Dreyfus JC, Poenaru L. Source: Biochemical and Biophysical Research Communications. 1978 November 29; 85(2): 615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=367369&dopt=Abstract

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Alpha-L-fucosidase and alpha-D-mannosidase activity in the white blood cells in the disease and carrier state of fucosidosis. Author(s): Matsuda I, Arashima S, Anakura M, Oka Y. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1973 September 28; 48(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4746732&dopt=Abstract

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Altered filtrability of white blood cells after myocardial infarction. Author(s): Bogar L, Mikita J, Nash GB, Smith MJ, Dormandy JA, Tekeres M. Source: Acta Med Hung. 1989; 46(2-3): 207-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2812961&dopt=Abstract

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Alternative exon 3 splicing of the human major protein zero gene in white blood cells and peripheral nerve tissue. Author(s): Besancon R, Prost AL, Konecny L, Latour P, Petiot P, Boutrand L, Kopp N, Mularoni A, Chamba G, Vandenberghe A. Source: Febs Letters. 1999 September 3; 457(3): 339-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10471804&dopt=Abstract

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Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms. Author(s): Marczynski B, Rihs HP, Rossbach B, Holzer J, Angerer J, Scherenberg M, Hoffmann G, Bruning T, Wilhelm M. Source: Carcinogenesis. 2002 February; 23(2): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872632&dopt=Abstract

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Analysis of DNA single-strand breaks in human venous blood: a technique which does not require isolation of white blood cells. Author(s): Hengstler JG, Fuchs J, Tanner B, Oesch-Bartlomowicz B, Holz C, Oesch F. Source: Environmental and Molecular Mutagenesis. 1997; 29(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9020308&dopt=Abstract

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Antibodies and thermolabile opsonins in the phagocytosis of human red and white blood cells pretreated with formaldehyde. Author(s): Nickolov C, Buckureshtliev A, Tsvetkov T, Minchev M, Milev A, Alexiev N, Tsonev L. Source: Folia Haematol Int Mag Klin Morphol Blutforsch. 1984; 111(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6202598&dopt=Abstract

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Aromatic deoxyribonucleic acid adducts in white blood cells of foundry and coke oven workers. Author(s): Hemminki K, Perera FP, Phillips DH, Randerath K, Reddy MV, Santella RM. Source: Scand J Work Environ Health. 1988; 14 Suppl 1: 55-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3393882&dopt=Abstract

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Aromatic DNA adducts in human white blood cells and skin after dermal application of coal tar. Author(s): Godschalk RW, Ostertag JU, Moonen EJ, Neumann HA, Kleinjans JC, van Schooten FJ. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1998 September; 7(9): 767-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9752984&dopt=Abstract

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Aromatic DNA adducts in white blood cells of coke workers. Author(s): Hemminki K, Grzybowska E, Chorazy M, Twardowska-Saucha K, Sroczynski JW, Putman KL, Randerath K, Phillips DH, Hewer A. Source: International Archives of Occupational and Environmental Health. 1990; 62(6): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2246066&dopt=Abstract

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Aromatic DNA adducts in white blood cells of foundry workers. Author(s): Hemminki K, Perera FP, Phillips DH, Randerath K, Reddy MV, Santella RM. Source: Iarc Sci Publ. 1988; (89): 190-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3143668&dopt=Abstract

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Ascorbic acid supplementation: its effects on body iron stores and white blood cells. Author(s): Malone HE, Kevany JP, Scott JM, O'Broin SD, O'Connor G. Source: Ir J Med Sci. 1986 March; 155(3): 74-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3519526&dopt=Abstract

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Assay of an interferon-induced enzyme in white blood cells as a diagnostic aid in viral diseases. Author(s): Schattner A, Wallach D, Merlin G, Hahn T, Levin S, Revel M. Source: Lancet. 1981 September 5; 2(8245): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6167829&dopt=Abstract

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Association between carcinogen-DNA adducts in white blood cells and lung cancer risk in the physicians health study. Author(s): Tang D, Phillips DH, Stampfer M, Mooney LA, Hsu Y, Cho S, Tsai WY, Ma J, Cole KJ, She MN, Perera FP. Source: Cancer Research. 2001 September 15; 61(18): 6708-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559540&dopt=Abstract

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Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms. Author(s): Whyatt RM, Perera FP, Jedrychowski W, Santella RM, Garte S, Bell DA. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2000 February; 9(2): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10698483&dopt=Abstract

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Attachment of cell fragments of Fusobacterium nucleatum to oral epithelial cells, gingival fibroblasts and white blood cells. Author(s): Falkler WA Jr, Smoot CN, Mongiello JR. Source: Archives of Oral Biology. 1982; 27(7): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6751304&dopt=Abstract

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Automated detection of malaria pigment in white blood cells for the diagnosis of malaria in Portugal. Author(s): Hanscheid T, Melo-Cristino J, Pinto BG. Source: The American Journal of Tropical Medicine and Hygiene. 2001 May-June; 64(56): 290-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463119&dopt=Abstract

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Banishing white blood cells. Safety group urges FDA to adopt new rules for prefiltering blood. Author(s): Becker C. Source: Modern Healthcare. 2001 February 19; 31(8): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234177&dopt=Abstract

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Behaviour of white blood cells and the complement system. Author(s): Falkenhagen D, Brown GS, Thomaneck U, Levin NW, Ivanovich P, Bergstrom J, Kishimoto T, Klinkmann H. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1993; 8 Suppl 2: 8-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8272252&dopt=Abstract

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Benzene-derived free radical--a possible mediator of its carcinogenicity. I. Ultrastructural and functional studies on the effect of benzene on human white blood cells and its possible prevention. Author(s): Kalir A, Bessler H, Braun R, Gitter S, Djaldetti M. Source: Isr J Med Sci. 1989 August; 25(8): 421-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2767948&dopt=Abstract

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Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells. Author(s): Zhou Q, Talaska G, Jaeger M, Bhatnagar VK, Hayes RB, Zenzer TV, Kashyap SK, Lakshmi VM, Kashyap R, Dosemeci M, Hsu FF, Parikh DJ, Davis B, Rothman N. Source: Mutation Research. 1997 October 24; 393(3): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9393612&dopt=Abstract

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Beta-adrenoceptor function in white blood cells from newborn infants: no relation to plasma catecholamine levels. Author(s): Boreus LO, Hjemdahl P, Lagercrantz H, Martinsson A, Yao AC. Source: Pediatric Research. 1986 November; 20(11): 1152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3025801&dopt=Abstract

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Blood sample stability at room temperature for counting red and white blood cells and platelets. Author(s): Vogelaar SA, Posthuma D, Boomsma D, Kluft C. Source: Vascular Pharmacology. 2002 August; 39(3): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616978&dopt=Abstract

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Calcium chelator Quin-2 prevents crocidolite-induced DNA strand breakage in human white blood cells. Author(s): Faux SP, Michelangeli F, Levy LS. Source: Mutation Research. 1994 December 1; 311(2): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7526185&dopt=Abstract

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Candida albicans infected aortic graft detected by indium-111 oxine labeled white blood cells. Author(s): Winzelberg GG. Source: Clinical Nuclear Medicine. 1984 December; 9(12): 734. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6509853&dopt=Abstract

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Carotene, carrots, and white blood cells. Author(s): Stampfer MJ, Willett W, Hennekens CH. Source: Lancet. 1982 September 11; 2(8298): 615. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6125763&dopt=Abstract

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Changes in immunological characteristics of white blood cells after administration of standardized mistletoe extract. Author(s): Klopp R, Schmidt W, Niemer W, Werner M, Beuth J. Source: In Vivo. 2001 November-December; 15(6): 447-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887328&dopt=Abstract

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Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos. Author(s): Marczynski B, Kraus T, Rozynek P, Schlosser S, Raithel HJ, Baur X. Source: International Archives of Occupational and Environmental Health. 2001 July; 74(5): 315-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516066&dopt=Abstract

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Changes in the flow properties of white blood cells after acute myocardial infarction. Author(s): Nash GB, Christopher B, Morris AJ, Dormandy JA. Source: British Heart Journal. 1989 November; 62(5): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2590586&dopt=Abstract

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Changes in total histamine content of white blood cells (WBC) in allergy patients. Author(s): Colldahl H. Source: Acta Allergol. 1973 December; 28(5): 316-32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4362209&dopt=Abstract

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Changes in white blood cells and myeloperoxidase activity in rhG-CSF prophylactic patients receiving cytotoxic chemotherapy. Author(s): Charuruks N, Krailadsiri P, Voravud N, Nitipaijit N, Srisink N, Settapiboon R. Source: J Med Assoc Thai. 1994 August; 77(8): 426-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7533203&dopt=Abstract

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Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. Author(s): Ladhani S, Lowe B, Cole AO, Kowuondo K, Newton CR. Source: British Journal of Haematology. 2002 December; 119(3): 839-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437669&dopt=Abstract

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Changes in white blood cells during parturition in mothers and newborn. Author(s): Delgado I, Neubert R, Dudenhausen JW. Source: Gynecologic and Obstetric Investigation. 1994; 38(4): 227-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7851806&dopt=Abstract

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Changes of white blood cells, immunosuppressive acidic protein, and interleukin-2 receptor after open heart surgery. Author(s): Chu SH, Hu RH, Lee YC, Chen KT. Source: The Thoracic and Cardiovascular Surgeon. 1995 April; 43(2): 94-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7545335&dopt=Abstract

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Characteristics of a specific radioimmunoassay for measurement of ferritin on the surface of peripheral mononuclear white blood cells in cancer patients. Author(s): Bluestein BI, Luderer AA, Hay N, Stundtner L, Boyle G, Carter AC. Source: J Immunoassay. 1984; 5(3-4): 159-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6530482&dopt=Abstract

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Characteristics of peripheral and peritoneal white blood cells in children with chronic renal failure, dialyzed or not. Author(s): Bouts AH, Out TA, Schroder CH, Monnens LA, Nauta J, Krediet RT, Davin JC. Source: Perit Dial Int. 2000 November-December; 20(6): 748-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216570&dopt=Abstract

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Chemical pathology of krabbe's disease. IV. Studies of galactosylceramide and lactosylceramide BETA-galactosidases in brain, white blood cells and aminotic fluid cells. Author(s): Svennerholm L, Hakansson G, Vanier MT. Source: Acta Paediatr Scand. 1975 July; 64(4): 649-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1155085&dopt=Abstract

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Circadian rhythm of white blood cells during clozapine treatment. Author(s): Ahokas A, Elonen E. Source: Psychopharmacology. 1999 June; 144(3): 301-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435399&dopt=Abstract

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Circulating white blood cells affect red cell pulmonary transit times in endurance athletes during intense exercise. Author(s): Zavorsky GS, Van Eeden SF, Walley KR, Russell JA. Source: Medicine and Science in Sports and Exercise. 2002 June; 34(6): 954-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048321&dopt=Abstract

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Clinical aspects of phagocytic activity of white blood cells. Author(s): Kiczka W, Szkaradkiewicz A. Source: Mater Med Pol. 1977 January-March; 9(1): 78-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=875460&dopt=Abstract

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Clinical evaluation in organ transplant patients of a polymerase chain reaction test for CMV DNA applied on white blood cells and serum. Author(s): Nyberg G, Bergstrom T, Blohme I, Norden G, Olofsson S, Ricksten A. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1994; 7(6): 428-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7865107&dopt=Abstract

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Clinical utility of measuring white blood cells on vaginal wet mount and endocervical gram stain for the prediction of chlamydial and gonococcal infections. Author(s): Moore SG, Miller WC, Hoffman IF, Fox KK, Owen-O'Dowd J, McPherson JT, Privette A, Schmitz JL, Leone PA. Source: Sexually Transmitted Diseases. 2000 October; 27(9): 530-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034527&dopt=Abstract

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Coke oven workers study: the effect of exposure and GSTM1 and NAT2 genotypes on DNA adduct levels in white blood cells and lymphocytes as determined by 32Ppostlabelling. Author(s): Binkova B, Topinka J, Mrackova G, Gajdosova D, Vidova P, Stavkova Z, Peterka V, Pilcik T, Rimar V, Dobias L, Farmer PB, Sram RJ. Source: Mutation Research. 1998 August 7; 416(1-2): 67-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725993&dopt=Abstract

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Colchicine and trimethylcolchicinic acid: a comparison of their effects on human white blood cells in vitro. Author(s): Wechsler R, Wallace SL, Gerber D, Scherrer J. Source: Arthritis and Rheumatism. 1965 December; 8(6): 1104-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5884819&dopt=Abstract

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Comparative studies on the distribution and intensity of cytoenzymatic reactions in neutrophilic white blood cells (heterophils) in some laboratory animals. Author(s): Godlewski A. Source: Folia Morphol (Warsz). 1976; 35(3): 335-45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1086277&dopt=Abstract

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Comparison of 99Tcm-HMPAO-labelled white blood cells and 67Ga citrate scans to detect myocarditis in the acute phase of Kawasaki disease. Author(s): Kao CH, Hsieh KS, Wang YL, Chen CW, Liao SQ, Wang SJ, Yeh SH. Source: Nuclear Medicine Communications. 1991 November; 12(11): 951-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1754155&dopt=Abstract

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Comparison of methods to enumerate white blood cells in semen. Author(s): Politch JA, Wolff H, Hill JA, Anderson DJ. Source: Fertility and Sterility. 1993 August; 60(2): 372-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8393411&dopt=Abstract

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Comparison of morphological changes in white blood cells after death and in vitro storage of blood for the estimation of postmortem interval. Author(s): Dokgoz H, Arican N, Elmas I, Fincanci SK. Source: Forensic Science International. 2001 December 15; 124(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741756&dopt=Abstract

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Comparison of the properties of phosphoribosylpyrophosphate synthetase in normal and leukemic human white blood cells. Author(s): Danks MK, Scholar EM. Source: Biochemical Pharmacology. 1979 September 15; 28(18): 2733-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=227412&dopt=Abstract

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Comparison of three methods to detect white blood cells in semen: leukocyte esterase dipstick test, granulocyte elastase enzymeimmunoassay, and peroxidase cytochemistry. Author(s): Wolff H, Panhans A, Zebhauser M, Meurer M. Source: Fertility and Sterility. 1992 December; 58(6): 1260-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1333995&dopt=Abstract

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Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood cells and involves reactive nitrogen intermediates. Author(s): Naotunne TS, Karunaweera ND, Mendis KN, Carter R. Source: Immunology. 1993 April; 78(4): 555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8495973&dopt=Abstract

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Cytotoxic mechanism in white blood cells. Author(s): Capsoni F, Meroni PL, Ciboddo GF, Colombo G. Source: The New England Journal of Medicine. 1979 January 4; 300(1): 44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=213721&dopt=Abstract

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Cytotoxicity of white blood cells activated by granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor and macrophage-colonystimulating factor against tumor cells in the presence of various monoclonal antibodies. Author(s): Ragnhammar P, Frodin JE, Trotta PP, Mellstedt H. Source: Cancer Immunology, Immunotherapy : Cii. 1994 October; 39(4): 254-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7525059&dopt=Abstract

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DA-DAPI positive heterochromatin in the interphase nuclei of human white blood cells. Author(s): Gruber K, Mayr B. Source: Haematologica. 1987 January-February; 72(1): 5-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3108096&dopt=Abstract

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Demonstration by flow cytometry of the numbers of residual white blood cells and platelets in filtered red blood cell concentrates and plasma preparations. Author(s): Neumuller J, Schwartz DW, Mayr WR. Source: Vox Sanguinis. 1997; 73(4): 220-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9407639&dopt=Abstract

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Detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in white blood cells of workers occupationally exposed to styrene. Author(s): Marczynski B, Rozynek P, Elliehausen HJ, Korn M, Baur X. Source: Archives of Toxicology. 1997; 71(8): 496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9248627&dopt=Abstract

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Detection of acute osteomyelitis with indium-111 labeled white blood cells in a patient with sickle cell disease. Author(s): Fernandez-Ulloa M, Vasavada PJ, Black RR. Source: Clinical Nuclear Medicine. 1989 February; 14(2): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2731401&dopt=Abstract

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Detection of adducts of deoxyribonucleic acid in white blood cells of roofers by 32Ppostlabeling. Relationship of adduct levels to measures of exposure to polycyclic aromatic hydrocarbons. Author(s): Herbert R, Marcus M, Wolff MS, Perera FP, Andrews L, Godbold JH, Rivera M, Stefanidis M, Lu XQ, Landrigan PJ, et al. Source: Scand J Work Environ Health. 1990 April; 16(2): 135-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2353197&dopt=Abstract

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Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Author(s): Fang JL, Vaca CE. Source: Carcinogenesis. 1997 April; 18(4): 627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9111191&dopt=Abstract

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Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patients with juvenile rheumatoid arthritis and childhood systemic lupus erythematosus. Author(s): Tsai YT, Chiang BL, Kao YF, Hsieh KH. Source: International Archives of Allergy and Immunology. 1995 March; 106(3): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7888786&dopt=Abstract

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Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. Author(s): Perera FP, Hemminki K, Young TL, Brenner D, Kelly G, Santella RM. Source: Cancer Research. 1988 April 15; 48(8): 2288-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3127049&dopt=Abstract

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Detection of single-strand breaks and base damage in DNA of human white blood cells as a tool for biological dosimetry of exposure to ionizing radiation. Author(s): van der Schans GP, Timmerman AJ, Bruijnzeel PL. Source: Military Medicine. 2002 February; 167(2 Suppl): 5-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873515&dopt=Abstract

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Diagnosis of infection by preoperative scintigraphy with indium-labeled white blood cells. Author(s): Wukich DK, Abreu SH, Callaghan JJ, Van Nostrand D, Savory CG, Eggli DF, Garcia JE, Berrey BH. Source: The Journal of Bone and Joint Surgery. American Volume. 1987 December; 69(9): 1353-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3126189&dopt=Abstract

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Diagnostic value of lung uptake of indium-111 oxine-labeled white blood cells. Author(s): Segall GM, McDougall IR. Source: Ajr. American Journal of Roentgenology. 1986 September; 147(3): 601-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3090866&dopt=Abstract

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Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers. Author(s): Godschalk RW, Maas LM, Van Zandwijk N, van 't Veer LJ, Breedijk A, Borm PJ, Verhaert J, Kleinjans JC, van Schooten FJ. Source: Carcinogenesis. 1998 May; 19(5): 819-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9635869&dopt=Abstract

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Differential apoptotic response to ionizing radiation in subpopulations of human white blood cells. Author(s): Wilkins RC, Wilkinson D, Maharaj HP, Bellier PV, Cybulski MB, McLean JR. Source: Mutation Research. 2002 January 15; 513(1-2): 27-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719087&dopt=Abstract

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Differential splicing of COL4A5 mRNA in kidney and white blood cells: a complex mutation in the COL4A5 gene of an Alport patient deletes the NC1 domain. Author(s): Guo C, Van Damme B, Van Damme-Lombaerts R, Van den Berghe H, Cassiman JJ, Marynen P. Source: Kidney International. 1993 December; 44(6): 1316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8301933&dopt=Abstract

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Distribution of acute bowel inflammation determined by technetium-labeled white blood cells in children with inflammatory bowel disease. Author(s): Charron M, Fernando del Rosario J, Kocoshis S. Source: Inflammatory Bowel Diseases. 1998 May; 4(2): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9589294&dopt=Abstract

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DNA adduct and mutation analysis in white blood cells of smokers and nonsmokers. Author(s): van Maanen JM, Maas LM, Hageman G, Kleinjans JC, van Agen B. Source: Environmental and Molecular Mutagenesis. 1994; 24(1): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8050415&dopt=Abstract

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DNA adducts in human nasal mucosa and white blood cells from smokers and nonsmokers. Author(s): Zhao C, Georgellis A, Flato S, Palmberg L, Thunberg E, Hemminki K. Source: Carcinogenesis. 1997 November; 18(11): 2205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395222&dopt=Abstract

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DNA damage by hydroquinone in human white blood cells: analysis by alkaline single-cell gel electrophoresis. Author(s): Andreoli C, Rossi S, Leopardi P, Crebelli R. Source: Mutation Research. 1999 January 2; 438(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9858677&dopt=Abstract

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DNA damage detected by the comet assay in the white blood cells of workers in a wooden furniture plant. Author(s): Palus J, Dziubaltowska E, Rydzynski K. Source: Mutation Research. 1999 July 21; 444(1): 61-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10477340&dopt=Abstract

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DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Author(s): Matullo G, Guarrera S, Carturan S, Peluso M, Malaveille C, Davico L, Piazza A, Vineis P. Source: International Journal of Cancer. Journal International Du Cancer. 2001 May 15; 92(4): 562-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304692&dopt=Abstract

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DNA strand-breaks induced by the topoisomerase I inhibitor camptothecin in unstimulated human white blood cells. Author(s): Daza P, Torreblanca J, Garcia-Herdugo G, Moreno FJ. Source: Cell Biology International. 2002; 26(8): 707-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175674&dopt=Abstract

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ECHOvirus 33 replication in human peripheral white blood cells. Author(s): Gnann JW Jr, Hayes EC, Smith JZ, Wilfert CM. Source: Journal of Medical Virology. 1979; 3(4): 291-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=479862&dopt=Abstract

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Effect of allopurinol on pyrimidine metabolism in human white blood cells. Role of the salvage pathway. Author(s): Banholzer P, Grobner W, Zollner N. Source: Advances in Experimental Medicine and Biology. 1979; 122B: 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=94760&dopt=Abstract

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Effect of cigarette smoking on white blood cells and erythrocyte enzymes. Author(s): Heinemann G, Schievelbein H, Eber S. Source: Archives of Environmental Health. 1982 September-October; 37(5): 261-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7138074&dopt=Abstract

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Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells. Author(s): Green MH, Lowe JE, Waugh AP, Aldridge KE, Cole J, Arlett CF. Source: Mutation Research. 1994 August; 316(2): 91-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7521006&dopt=Abstract

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Effect of high doses of glucocorticoids on the kinetics of human white blood cells in vivo. Author(s): Mollmann HW, Rohdewald P, Barth J, Derendorf H. Source: Medizinische Klinik (Munich, Germany : 1983). 1988 March 4; 83(5): 159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3374441&dopt=Abstract

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Effect of physical effort on the white blood cells in benign familial leukopenia. Author(s): Shoenfeld Y, Aloni D, Keren G, Shaklai M, Djaldetti M, Pinkhas J. Source: Acta Haematologica. 1981; 65(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6785955&dopt=Abstract

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Effects of betamethasone on white blood cells in patients with premature rupture of the membranes and preterm labor. Author(s): Ferguson JE 2nd, Hensleigh PA, Gill P. Source: American Journal of Obstetrics and Gynecology. 1984 October 15; 150(4): 439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6486210&dopt=Abstract

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Effects of metal ions on white blood cells of patients with failed total joint arthroplasties. Author(s): Savarino L, Granchi D, Ciapetti G, Stea S, Donati ME, Zinghi G, Fontanesi G, Rotini R, Montanaro L. Source: Journal of Biomedical Materials Research. 1999 December 15; 47(4): 543-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10497290&dopt=Abstract

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Effects of monochromatic ultraviolet irradiation (300-400 nm) on viability of human white blood cells. Author(s): Walther T, Gast W, Rytter M, Haustein UF, Biella U. Source: Photodermatology, Photoimmunology & Photomedicine. 1990 April; 7(2): 88-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2400681&dopt=Abstract

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Effects of platelets and white blood cells and antiplatelet agent C7E3 (Reopro) on a new test of PAF procoagulant activity of whole blood. Author(s): Despotis GJ, Ikonomakou S, Levine V, Joiner-Maier D, Santoro SA, Joist JH. Source: Thrombosis Research. 1997 May 1; 86(3): 205-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9175242&dopt=Abstract

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Effects of short heat exposure on human red and white blood cells. Author(s): Fildes J, Fisher S, Sheaff CM, Barrett JA. Source: The Journal of Trauma. 1998 September; 45(3): 479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751536&dopt=Abstract

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Effects of white blood cells on the in vitro penetration of zona-free hamster eggs by human spermatozoa. Author(s): Maruyama DK Jr, Hale RW, Rogers BJ. Source: Journal of Andrology. 1985 March-April; 6(2): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3838741&dopt=Abstract

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Elastic properties of passive leukemic white blood cells. Author(s): Paulitschke M, Mikita J, Lerche D, Meier W. Source: Int J Microcirc Clin Exp. 1991 February; 10(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2019485&dopt=Abstract

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Endovascular abdominal aortic aneurysm repair induces significant alterations in surface adhesion molecule expression on donor white blood cells exposed to patient plasma. Author(s): Swartbol P, Norgren L, Parsson H, Truedsson L. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 1997 July; 14(1): 48-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9290560&dopt=Abstract

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Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy. Comparison of three labelling methods. Author(s): Mortelmans L, Verbruggen A, Malbrain S, Heynen MJ, de Bakker C, Boogaerts M, de Roo M. Source: European Journal of Nuclear Medicine. 1988; 14(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3136018&dopt=Abstract

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Evaluation of two 111In-oxinate formulations for labelling of white blood cells. Author(s): Leners N, Ferrant A, Jamar F. Source: Int J Rad Appl Instrum B. 1991; 18(7): 727-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1787081&dopt=Abstract

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Ex vivo activation and retransfusion of white blood cells. The immunotherapy of cancer. Author(s): Hamblin TJ. Source: Curr Stud Hematol Blood Transfus. 1990; (57): 249-66. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2272205&dopt=Abstract

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Expression and modulation of homologous restriction factor (HRF) on peripheral white blood cells. Author(s): Sayama K, Zalman LS, Muller-Eberhard HJ, Gigli I. Source: Trans Assoc Am Physicians. 1988; 101: 270-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2855898&dopt=Abstract

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Expression of CD80 (B7/BB-1) and CD28 in human white blood cells treated with urocanic acid. Author(s): Laihia JK, Uksila J, Luhtala M, Jansen CT. Source: Archives of Dermatological Research. 1996 September; 288(10): 570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8919038&dopt=Abstract

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Extracorporeal plateletpheresis induces the interaction of activated platelets with white blood cells. Author(s): Gutensohn K, Alisch A, Krueger W, Kroeger N, Kuehnl P. Source: Vox Sanguinis. 2000; 78(2): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765145&dopt=Abstract

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Falciparum malaria in naturally infected human patients: IV--Ultrastructural changes in peripheral white blood cells. Author(s): el-Shoura SM. Source: Ann Parasitol Hum Comp. 1993; 68(4): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8154781&dopt=Abstract

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Five-year prospective study of peripheral white blood cells in infectious mononucleosis. Author(s): Janeczko J. Source: Acta Med Pol. 1985; 26(3-4): 141-52. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3837609&dopt=Abstract

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Flow cytochemical patterns of white blood cells in human haematopoietic malignancies. I. Acute leukaemias. Author(s): Drewinko B, Bollinger P, Brailas C, Moyle S, Wyatt J, Simson E, Johnston D, Trujillo JM. Source: British Journal of Haematology. 1987 May; 66(1): 27-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3593655&dopt=Abstract

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Flow cytochemical patterns of white blood cells in human haematopoietic malignancies. II. Chronic leukaemias. Author(s): Drewinko B, Bollinger P, Brailas C, Wyatt J, Simson E, Trujillo JM. Source: British Journal of Haematology. 1987 October; 67(2): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3479189&dopt=Abstract

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Flow cytochemical patterns of white blood cells in human hematopoietic malignancies: III. Miscellaneous hemopoietic diseases. Author(s): Drewinko B, Bollinger P, Brailas C, Wyatt J, Simson E, Trujillo JM. Source: Blood Cells. 1988; 13(3): 475-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3382753&dopt=Abstract

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Flow properties of white blood cells. Author(s): Ciuffetti G, Mercuri M, Rizzo MT, Lombardini R. Source: Bmj (Clinical Research Ed.). 1988 July 23; 297(6643): 292. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3416156&dopt=Abstract

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Fluorescent male sex chromatin in white blood cells. Author(s): Hale MT, Vaughn WK, Engel E. Source: Southern Medical Journal. 1973 March; 66(3): 340-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4120578&dopt=Abstract

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Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Author(s): Birnboim HC, Jevcak JJ. Source: Cancer Research. 1981 May; 41(5): 1889-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7214357&dopt=Abstract

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Formation of aromatic DNA adducts in white blood cells in relation to urinary excretion of 1-hydroxypyrene during consumption of grilled meat. Author(s): van Maanen JM, Moonen EJ, Maas LM, Kleinjans JC, van Schooten FJ. Source: Carcinogenesis. 1994 October; 15(10): 2263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955064&dopt=Abstract

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Formation of polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells during consumption of charcoal-broiled beef. Author(s): Rothman N, Poirier MC, Baser ME, Hansen JA, Gentile C, Bowman ED, Strickland PT. Source: Carcinogenesis. 1990 July; 11(7): 1241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2372884&dopt=Abstract

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Functional significance of white blood cells in the male and female reproductive tract. Author(s): Barratt CL, Bolton AE, Cooke ID. Source: Human Reproduction (Oxford, England). 1990 August; 5(6): 639-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2254398&dopt=Abstract

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Galactose-I-phosphate uridyltransferase in red and white blood cells. Author(s): Inouye T, Nadler HL, Hsia YY. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1968 February; 19(2): 169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5645487&dopt=Abstract

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Genotoxic effects of styrene-7,8-oxide in human white blood cells: comet assay in relation to the induction of sister-chromatid exchanges and micronuclei. Author(s): Laffon B, Pasaro E, Mendez J. Source: Mutation Research. 2001 April 5; 491(1-2): 163-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287309&dopt=Abstract

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Glycogenosis type 6 (liver phosphorylase deficiency). A case followed for ten years, with normal phosphorylase activity in white blood cells and jejunal mucosa. Author(s): Ockerman PA, Jelke H, Kaijser K. Source: Acta Paediatr Scand. 1966 January; 55(1): 10-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5223676&dopt=Abstract

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Hepatitis B virus DNA in liver and white blood cells of patients with hepatoma. Author(s): Lie-Injo LE, Balasegaram M, Lopez CG, Herrera AR. Source: Dna. 1983; 2(4): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6319100&dopt=Abstract

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Heterozygote testing in cystic fibrosis. Metachromasia in cultured white blood cells. Author(s): Geisler M, Bender SW, Mohrmann C, Svejcar J, Degenhardt KH, Hoevels O. Source: Z Kinderheilkd. 1972; 112(2): 133-41. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4112462&dopt=Abstract

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High dietary omega-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA base adducts in white blood cells of female subjects. Author(s): Nair J, Vaca CE, Velic I, Mutanen M, Valsta LM, Bartsch H. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1997 August; 6(8): 597-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9264272&dopt=Abstract

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Histological study of white blood cells and their association with lipodermatosclerosis and venous ulceration. Author(s): Scott HJ, Coleridge Smith PD, Scurr JH. Source: The British Journal of Surgery. 1991 February; 78(2): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2015476&dopt=Abstract

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How do normal and leukemic white blood cells egress from the bone marrow? Morphological facts and biochemical riddles. Author(s): Petrides PE, Dittmann KH. Source: Blut. 1990 July; 61(1): 3-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2201412&dopt=Abstract

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How white blood cells are collected. Author(s): Baez D, Grant J. Source: Nursing. 1976 June; 6(6): 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1046154&dopt=Abstract

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HPLC/fluorescence determination of anti-BPDE-DNA adducts in mononuclear white blood cells from PAH-exposed humans. Author(s): Pavanello S, Favretto D, Brugnone F, Mastrangelo G, Dal Pra G, Clonfero E. Source: Carcinogenesis. 1999 March; 20(3): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10190558&dopt=Abstract

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Human cytomegalovirus DNA kinetics using a novel HCMV DNA quantitative assay in white blood cells of immunocompromised patients under Ganciclovir therapy. Author(s): Payan C, Veal N, Sarol L, Villarme M, Ngohou C, Riberi P, Francois S, Ifrah N, Loison J, Chennebault JM, Pichard E, Kouyoumdjian S, Lunel F. Source: Journal of Virological Methods. 1997 April; 65(1): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9128870&dopt=Abstract

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Human serotonectin: a blood glycoprotein that binds serotonin and is associated with platelets and white blood cells. Author(s): Tamir H, Payette RF, Huang YL, Liu KP, Gershon MD. Source: Journal of Cell Science. 1985 February; 73: 187-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4019592&dopt=Abstract

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Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection. Author(s): Lei XD, Kaufman S. Source: Biochemical and Biophysical Research Communications. 1998 July 20; 248(2): 432-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9675155&dopt=Abstract

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Human white blood cells contain cyclobutyl pyrimidine dimer photolyase. Author(s): Sutherland BM, Bennett PV. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 October 10; 92(21): 9732-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7568207&dopt=Abstract

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Immunochemical detection of adducts of sulfur mustard to DNA of calf thymus and human white blood cells. Author(s): van der Schans GP, Scheffer AG, Mars-Groenendijk RH, Fidder A, Benschop HP, Baan RA. Source: Chemical Research in Toxicology. 1994 May-June; 7(3): 408-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8075373&dopt=Abstract

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Increased adhesiveness of white blood cells in patients with unstable angina: additional evidence for an involvement of the immune-inflammatory system. Author(s): Leibovitz E, Hertz Y, Liberman E, Sclarovsky S, Berliner S. Source: Clin Cardiol. 1997 December; 20(12): 1017-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9422840&dopt=Abstract

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Increased brain-derived neurotrophic factor expression in white blood cells of relapsing-remitting multiple sclerosis patients. Author(s): Gielen A, Khademi M, Muhallab S, Olsson T, Piehl F. Source: Scandinavian Journal of Immunology. 2003 May; 57(5): 493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753507&dopt=Abstract

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Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: further evidence for smoldering inflammation in patients with atherosclerosis. Author(s): Kassirer M, Zeltser D, Prochorov V, Schoenman G, Frimerman A, Keren G, Shapira I, Miller H, Roth A, Arber N, Eldor A, Berliner S. Source: American Heart Journal. 1999 September; 138(3 Pt 1): 555-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467208&dopt=Abstract

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Indium-labeled white blood cells apheresed from donors receiving G-CSF localize to sites of inflammation when infused into allogeneic bone marrow transplant recipients. Author(s): Adkins D, Goodgold H, Hendershott L, Johnston M, Cravens D, Spitzer G. Source: Bone Marrow Transplantation. 1997 April; 19(8): 809-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9134173&dopt=Abstract

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White Blood Cells

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Induction of DNA strand breaks by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)furanone and humic substances in relation to glutathione and calcium status in human white blood cells. Author(s): Nunn JW, Chipman JK. Source: Mutation Research. 1994 December; 341(2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7527490&dopt=Abstract

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Influence of aging and neurodegenerative disease on changes in band 3-like proteins in white blood cells. Author(s): Bosman GJ, Steetzel BD, De Man AJ, Van Kalmthout PJ, Visser FE, De Grip WJ. Source: Mechanisms of Ageing and Development. 1995 April 21; 80(1): 43-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7564560&dopt=Abstract

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Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells. Author(s): Phillips DH, Schoket B, Hewer A, Bailey E, Kostic S, Vincze I. Source: International Journal of Cancer. Journal International Du Cancer. 1990 October 15; 46(4): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2210880&dopt=Abstract

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Influence of dietary fatty acid, vegetable, and vitamin intake on etheno-DNA adducts in white blood cells of healthy female volunteers: a pilot study. Author(s): Hagenlocher T, Nair J, Becker N, Korfmann A, Bartsch H. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2001 November; 10(11): 1187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700267&dopt=Abstract

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Influence of GSTM1 genotypes on anti-BPDE-DNA adduct levels in mononuclear white blood cells of humans exposed to PAH. Author(s): Pavanello S, Gabbani G, Mastrangelo G, Brugnone F, Maccacaro G, Clonfero E. Source: International Archives of Occupational and Environmental Health. 1999 July; 72(4): 238-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10491778&dopt=Abstract

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Influence of white blood cells on the fibrinolytic response to sepsis: studies of septic patients with or without severe leucopenia. Author(s): Haj MA, Neilly IJ, Robbie LA, Adey GD, Bennett B. Source: British Journal of Haematology. 1995 July; 90(3): 541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7646991&dopt=Abstract

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Influence of white blood cells on the filterability of human erythrocytes: modelling of the filtration process and experimental results. Author(s): Kucera W, Wegner G, Lerche D. Source: Biomed Biochim Acta. 1991; 50(2): 159-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1877976&dopt=Abstract

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Inositol 1,4,5-trisphosphate synthesis in mononuclear white blood cells of malignant hyperthermia-susceptible and normal human beings, following in vitro exposure to halothane, caffeine and ryanodine. Author(s): Martens U, Krause T, Scholz J, Wappler F, Steinrucke K, am Esch JS. Source: European Journal of Anaesthesiology. 2000 June; 17(6): 364-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928436&dopt=Abstract

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Interference of patient medication in the radiolabelling of white blood cells: an update. Author(s): Sampson CB. Source: Nuclear Medicine Communications. 1998 June; 19(6): 529-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10234656&dopt=Abstract

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Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption. Author(s): Kang DH, Rothman N, Poirier MC, Greenberg A, Hsu CH, Schwartz BS, Baser ME, Groopman JD, Weston A, Strickland PT. Source: Carcinogenesis. 1995 May; 16(5): 1079-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7767968&dopt=Abstract

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Interleukin-1 alpha inhibition of luteinized human granulosa cell progesterone production through influences on associated white blood cells. Author(s): Best CL, Hill JA. Source: Recent Progress in Hormone Research. 1995; 50: 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7740171&dopt=Abstract

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Intracellular degradation of sulforhodamine-GM1: use for a fluorescence-based characterization of GM2-gangliosidosis variants in fibroblasts and white blood cells. Author(s): Agmon V, Khosravi R, Marchesini S, Dinur T, Dagan A, Gatt S, Navon R. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1996 March 29; 247(1-2): 105-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8920231&dopt=Abstract

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Intraindividual comparison of 99mTc-labelled anti-SSEA-1 antigranulocyte antibody and 99mTc-HMPAO labelled white blood cells for the imaging of infection. Author(s): Gratz S, Behr T, Herrmann A, Dresing K, Tarditi L, Franceschini R, Rhodes B, Sturmer KM, Becker W. Source: European Journal of Nuclear Medicine. 1998 April; 25(4): 386-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9553168&dopt=Abstract

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Isocratic ion-exchange chromatographic assay for the nucleotide gemcitabine triphosphate in human white blood cells. Author(s): Sparidans RW, Crul M, Schellens JH, Beijnen JH. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 November 25; 780(2): 423-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401370&dopt=Abstract

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Isolation and labelling of white blood cells. Author(s): Gunasekera RD, Peters AM. Source: Nuclear Medicine Communications. 1997 June; 18(6): 589-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9259535&dopt=Abstract

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Jordans' anomaly in white blood cells. Report of case. Author(s): Rozenszajn L, Klajman A, Yaffe D, Efrati P. Source: Blood. 1966 August; 28(2): 258-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5330405&dopt=Abstract

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L1 effects on reactive oxygen (ROS) and nitrogen species (RNS) release, hemoglobin oxidation, low molecular weight antioxidants, and antioxidant enzyme activities in red and white blood cells of thalassemic patients. Author(s): Korkina L, De Luca C, Deeva I, Perrotta S, Nobili B, Passi S, Puddu P. Source: Transfusion Science. 2000 December; 23(3): 253-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099907&dopt=Abstract

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Lack of mitochondrial enzymes of the urea cycle in human white blood cells. Author(s): Rabier D, Cathelineau L, Kamoun P. Source: Pediatric Research. 1979 March; 13(3): 207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=224369&dopt=Abstract

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Lack of proliferation of circulating white blood cells in patients with syphilis before and after a Jarisch-Herxheimer reaction. Author(s): Horsmanheimo M. Source: Br J Vener Dis. 1978 August; 54(4): 225-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=678954&dopt=Abstract

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Lack of specific receptors for C-reactive protein on white blood cells. Author(s): Hundt M, Zielinska-Skowronek M, Schmidt RE. Source: European Journal of Immunology. 2001 December; 31(12): 3475-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745367&dopt=Abstract

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Large granules and lysosomal fusion in human Chediak-Higashi white blood cells. Author(s): Rozenszajn LA, David EB, Sela SB. Source: Acta Haematologica. 1977; 57(5): 279-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=66833&dopt=Abstract

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Letter: Drug-induced morphological changes in white blood cells. Author(s): Polite AL Jr, Cottrell JC, Lowry B, Reisman L. Source: Am J Med Technol. 1975 March; 41(3): 130-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1115092&dopt=Abstract

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Leukogram and white blood cells count in native people of Chukotka. Author(s): Gyrgolkay LA, Nikitin YP. Source: Int J Circumpolar Health. 2001 November; 60(4): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768431&dopt=Abstract

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Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany. Author(s): Marczynski B, Rozynek P, Kraus T, Schlosser S, Raithel HJ, Baur X. Source: Mutation Research. 2000 July 10; 468(2): 195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882896&dopt=Abstract

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Linoleic acid levels in white blood cells, platelets, and serum of multiple sclerosis patients. Author(s): Fisher M, Johnson MH, Natale AM, Levine PH. Source: Acta Neurologica Scandinavica. 1987 October; 76(4): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3687373&dopt=Abstract

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Lipid-laden white blood cells in the circulation of patients with coronary heart disease. Author(s): Tertov VV, Kalenich OS, Orekhov AN. Source: Experimental and Molecular Pathology. 1992 August; 57(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1397191&dopt=Abstract

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Lithium levels in white blood cells and their relationship to observed side effects. Author(s): Ong YL. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1983 July; 143: 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6882991&dopt=Abstract

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Localization of DNA in ultrascopic nuclear appendages of polymorphonuclear white blood cells from patients with low serum B(12). Author(s): Bunting RW, Selig MK. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2002 October; 50(10): 1381-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364571&dopt=Abstract

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Locomotion of white blood cells: a biophysical analysis. Author(s): de Boisfleury-Chevance A, Rapp B, Gruler H. Source: Blood Cells. 1989; 15(2): 315-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2765669&dopt=Abstract

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Longitudinal relation between smoking and white blood cells. Author(s): Sunyer J, Munoz A, Peng Y, Margolick J, Chmiel JS, Oishi J, Kingsley L, Samet JM. Source: American Journal of Epidemiology. 1996 October 15; 144(8): 734-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8857822&dopt=Abstract

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Maternal effects on behavior and white blood cells of isolated female mice. Author(s): Weltman AS, Sackler AM, Schwartz R. Source: Life Sciences. 1970 March 1; 9(5): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5462231&dopt=Abstract

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Measurement of DNA breaks and oxidative damage in polymorphonuclear and mononuclear white blood cells: a novel approach using the comet assay. Author(s): Giovannelli L, Pitozzi V, Riolo S, Dolara P. Source: Mutation Research. 2003 July 8; 538(1-2): 71-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834756&dopt=Abstract

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Measurement of oestrone sulphatase activity in white blood cells to monitor in vivo inhibition of steroid sulphatase activity by oestrone-3-O-sulphamate. Author(s): Purohit A, Froome VA, Wang DY, Potter BV, Reed MJ. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1997 May; 62(1): 4551. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366497&dopt=Abstract

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Measurement of the immune response to an allograft: amino acid incorporation by peripheral white blood cells in man. Author(s): Blamey RW, Bennett RC, Singer AM, Nicol R, Harrison J. Source: The British Journal of Surgery. 1975 November; 62(11): 863-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1104045&dopt=Abstract

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Medical myth: Measuring white blood cells in the stools is useful in the management of acute diarrhea. Author(s): Herbert ME. Source: The Western Journal of Medicine. 2000 June; 172(6): 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854401&dopt=Abstract

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Methionine-activating enzyme and catechol-O-methyl transferase activity in normal and leukemic white blood cells. Author(s): Baldessarini RJ, Bell WR. Source: Nature. 1966 January 1; 209(18): 78-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5224275&dopt=Abstract

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Methotrexate-induced neurotoxicity: appearance on indium-111-white blood cells, gallium-67-citrate and thallium-201-chloride scintigraphy. Author(s): Even-Sapir E, Barnes DC, Llewellyn CG, Langley GR. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1993 August; 34(8): 1377-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8326402&dopt=Abstract

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Methyl DNA adducts, DNA repair, and hypoxanthine-guanine phosphoribosyl transferase mutations in peripheral white blood cells from patients with malignant melanoma treated with dacarbazine and hydroxyurea. Author(s): Philip PA, Souliotis VL, Harris AL, Salisbury A, Tates AD, Mitchell K, van Delft JH, Ganesan TS, Kyrtopoulos SA. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1996 February; 2(2): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9816173&dopt=Abstract

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Microcirculation in venous disorders: the role of the white blood cells. Author(s): Dormandy JA. Source: Int J Microcirc Clin Exp. 1995; 15 Suppl 1: 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8748882&dopt=Abstract

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Mitogenic effect of tumour antigen in cultures of white blood cells from subjects immunized with helaantigen. Author(s): Bjorklund B, Bjorklund V, Lundstrom R. Source: Acta Pathol Microbiol Scand [b] Microbiol Immunol. 1971; 79(3): 442. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5283064&dopt=Abstract

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Modulation of DNA adduct levels in human mononuclear white blood cells and granulocytes by CYP1A1 CYP2D6 and GSTM1 genetic polymorphisms. Author(s): Butkiewicz D, Grzybowska E, Hemminki K, Ovrebo S, Haugen A, Motykiewicz G, Chorazy M. Source: Mutation Research. 1998 July 8; 415(1-2): 97-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711266&dopt=Abstract

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Modulation of human granulosa cell steroid production in vitro by tumor necrosis factor alpha: implications of white blood cells in culture. Author(s): Best CL, Pudney J, Anderson DJ, Hill JA. Source: Obstetrics and Gynecology. 1994 July; 84(1): 121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8008306&dopt=Abstract

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Molecular weight characterization of beta-D-glucocerebrosidase in mononuclear white blood cells in Gaucher's disease. Author(s): Pirruccello S, Barranger JA, Barton NW, Brady RO, Ginns EI. Source: Biochem Med. 1984 February; 31(1): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6743300&dopt=Abstract

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Monitoring normal and malignant human white blood cells by the use of linear programmed thermal degradation mass spectrometry. Author(s): Yergey AL, Risby TH, Golomb HM. Source: Biomed Mass Spectrom. 1978 January; 5(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=272206&dopt=Abstract

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Monitoring occupational exposure to carcinogens: detection by 32P-postlabelling of aromatic DNA adducts in white blood cells from iron foundry workers. Author(s): Phillips DH, Hemminki K, Alhonen A, Hewer A, Grover PL. Source: Mutation Research. 1988 March; 204(3): 531-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3347220&dopt=Abstract

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Monitoring of interferon therapy by assay of (2'--5') oligo-isoadenylate synthetase in human peripheral white blood cells. Author(s): Schattner A, Merlin G, Wallach D, Rosenberg H, Bino T, Hahn T, Levin S, Revel M. Source: Journal of Interferon Research. 1981; 1(4): 587-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6180091&dopt=Abstract

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Mosaic mongolism with normal chromosomal complement in the white blood cells. Author(s): Zellweger H, Abbo G, Nielsen MK, Wallwork K. Source: Humangenetik. 1966; 2(4): 323-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4225289&dopt=Abstract

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Multiple forms of PRPP synthetase in human leukemic white blood cells seen with isoelectric focusing. Author(s): Danks MK, Scholar EM. Source: Int J Biochem. 1981; 13(12): 1261-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6274720&dopt=Abstract

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Multiple sequential thresholds technique in automated white blood cells classification. Author(s): Bao HF, Gelsema ES, den Harink HC, Smeulders AW. Source: J Tongji Med Univ. 1987; 7(4): 208-13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3448249&dopt=Abstract

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Natural fluorescence of white blood cells: spectroscopic and imaging study. Author(s): Monici M, Pratesi R, Bernabei PA, Caporale R, Ferrini PR, Croce AC, Balzarini P, Bottiroli G. Source: Journal of Photochemistry and Photobiology. B, Biology. 1995 September; 30(1): 29-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558361&dopt=Abstract

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Negative regulator of pluripotent hematopoietic stem cell proliferation in human white blood cells and plasma as analysed by enzyme immunoassay. Author(s): Pradelles P, Frobert Y, Creminon C, Liozon E, Masse A, Frindel E. Source: Biochemical and Biophysical Research Communications. 1990 August 16; 170(3): 986-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2202303&dopt=Abstract

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No acute impact of haemodialysis treatment on free radical scavenging enzyme gene expression in white blood cells. Author(s): Schettler V, Kuhn W, Kleinoeder T, Armstrong VW, Oellerich M, Muller GA, Wieland E. Source: Journal of Internal Medicine. 2003 February; 253(2): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542561&dopt=Abstract

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No acute impact of lipid apheresis treatment on free radical scavenging enzyme gene expression in white blood cells. Author(s): Schettler V, Krontal J, Scheel A, Wieland E. Source: European Journal of Clinical Investigation. 2003 February; 33(2): 134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588287&dopt=Abstract

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Non-infectious cause of intense diffuse pulmonary uptake of indium-111 oxine labelled white blood cells. Author(s): Klonecke AS. Source: Nuclear Medicine Communications. 1990 August; 11(8): 573-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2120640&dopt=Abstract

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Numerical changes in the various peripheral white blood cells in children as a result of antineoplastic therapy. Author(s): Cranendonk E, van Gennip AH, Abeling NG, Behrendt H. Source: Acta Haematologica. 1984; 72(5): 315-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6098118&dopt=Abstract

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Opioid receptors on white blood cells: effect of HIV infection and methadone treatment. Author(s): Beck M, Mirmohammadsadegh A, Franz B, Blanke J, Hengge UR. Source: Pain. 2002 July; 98(1-2): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098631&dopt=Abstract

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Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus. Author(s): Walsh DS, Myint KS, Kantipong P, Jongsakul K, Watt G. Source: The American Journal of Tropical Medicine and Hygiene. 2001 December; 65(6): 899-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791995&dopt=Abstract

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Ornithine transcarbamylase (OTC) in white blood cells and jejunal mucosa. Author(s): Nagata N, Akaboshi I, Yamamoto J, Endo F, Matsuda I, Katsuki T. Source: Advances in Experimental Medicine and Biology. 1982; 153: 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7164921&dopt=Abstract

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Ornithine transcarbamylase (OTC) in white blood cells. Author(s): Nagata N, Akaboshi I, Yamamoto J, Matsuda I, Ohtsuka H, Katsuki T. Source: Pediatric Research. 1980 December; 14(12): 1370-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7208155&dopt=Abstract

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Oxidative DNA damage in human white blood cells in dietary antioxidant intervention studies. Author(s): Moller P, Loft S. Source: The American Journal of Clinical Nutrition. 2002 August; 76(2): 303-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144999&dopt=Abstract

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Participation of serum albumin and LDL-cholesterol in impaired blood cellfilterability affected by white blood cells in patients with cerebral thrombosis. Author(s): Yoshida H, Takamatsu S, Satoh K, Imaizumi T, Hiramoto M, Shoji B. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1992 November; 52(7): 641-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1455156&dopt=Abstract

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PCR amplification of HIV and cellular DNA sequences in formaldehyde-fixed, immunoreactive white blood cells. Author(s): Fitzgerald LM, Yin HZ, Kiessling AA. Source: Biotechniques. 1993 July; 15(1): 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8363828&dopt=Abstract

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Pediatric inflammatory bowel disease imaged with Tc-99m white blood cells. Author(s): Charron M. Source: Clinical Nuclear Medicine. 2000 September; 25(9): 708-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983760&dopt=Abstract

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Pediatric inflammatory bowel disease: assessment with scintigraphy with 99mTc white blood cells. Author(s): Charron M, del Rosario FJ, Kocoshis SA. Source: Radiology. 1999 August; 212(2): 507-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10429710&dopt=Abstract

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Peripheral white blood cells and HPA axis neurohormones in major depression. Author(s): Darko DF, Gillin JC, Risch SG, Golshan S, Bulloch K, Baird SM. Source: The International Journal of Neuroscience. 1989 March; 45(1-2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2541094&dopt=Abstract

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Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1hydroxypyrene in foundry workers. Author(s): Santella RM, Hemminki K, Tang DL, Paik M, Ottman R, Young TL, Savela K, Vodickova L, Dickey C, Whyatt R, et al. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1993 January-February; 2(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8420613&dopt=Abstract

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Polycyclic aromatic hydrocarbon--DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung. Author(s): van Schooten FJ, Hillebrand MJ, van Leeuwen FE, van Zandwijk N, Jansen HM, den Engelse L, Kriek E. Source: Carcinogenesis. 1992 June; 13(6): 987-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1600621&dopt=Abstract

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Polymerase chain reaction detection of Chlamydia pneumoniae in circulating white blood cells. Author(s): Boman J, Gaydos CA. Source: The Journal of Infectious Diseases. 2000 June; 181 Suppl 3: S452-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839737&dopt=Abstract

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Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells. Author(s): Butkiewicz D, Grzybowska E, Phillips DH, Hemminki K, Chorazy M. Source: Environmental and Molecular Mutagenesis. 2000; 35(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712743&dopt=Abstract

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Possible feedback control of white blood cells: effect of splenectomy in Felty's syndrome. Author(s): Spencer RP. Source: Medical Hypotheses. 1998 May; 50(5): 415-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9681921&dopt=Abstract

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Possible role of fibrinogen in the aggregation of white blood cells. Author(s): Berliner S, Fuchs J, Seligsohn U, Kariv N, Hazaz B, Rotenberg Z, Weinberger I, Agmon J, Pinkhas J, Aronson M. Source: Thrombosis and Haemostasis. 1987 August 4; 58(2): 749-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3672427&dopt=Abstract

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Postlabeling analysis of DNA adducts in white blood cells from lead smelter workers. Author(s): Ichiba M, Oishi H, Wang Y, Iyadomi M, Tomokuni K. Source: Ind Health. 1994; 32(4): 253-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7591855&dopt=Abstract

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Postlabeling analysis of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. Author(s): Reddy MV, Hemminki K, Randerath K. Source: Journal of Toxicology and Environmental Health. 1991 October; 34(2): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1920524&dopt=Abstract

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Postlabeling and immunoassay analysis of polycyclic aromatic hydrocarbons-adducts of deoxyribonucleic acid in white blood cells of foundry workers. Author(s): Hemminki K, Randerath K, Reddy MV, Putman KL, Santella RM, Perera FP, Young TL, Phillips DH, Hewer A, Savela K. Source: Scand J Work Environ Health. 1990 June; 16(3): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2382118&dopt=Abstract

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Postoperative infections after neurosurgery and cardiosurgery: the value of labelled white blood cells. Author(s): Sacchetti GM, Rudoni M, Baroli A, Musiani A, Franchini L, Antonini G, Ciardi L, Boccardi A, Gandini G, Bellotti C, et al. Source: Q J Nucl Med. 1995 December; 39(4): 274-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624789&dopt=Abstract

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Presence of connectin-like protein in white blood cells and platelets. Author(s): Hashimoto K, Kamitani T, Wada Y, Tatsumi N. Source: The Tohoku Journal of Experimental Medicine. 1984 May; 143(1): 59-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6379988&dopt=Abstract

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Proceedings: Ferritin in normal and leukaemic white blood cells. Author(s): Parry H, Summers M, Worwood M, Jacobs A. Source: British Journal of Haematology. 1974 June; 27(2): 361. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4843683&dopt=Abstract

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Proliferation of white blood cells in the blood of human renal allograft recipients. Lack of correlation with acute rejection episodes. Author(s): Hayry P, Lalla M, Pasternack A, Virolainen M. Source: Ann Clin Res. 1972 April; 4(2): 100-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4554943&dopt=Abstract

86

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Prolonged storage of white blood cells in frozen state for transfusion. Author(s): Vinograd-Finkel FR, Kisselev AE, Leontovich VA, Abezgauz NN. Source: Bibl Haematol. 1968; 29: 719-26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4973337&dopt=Abstract

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Pseudohyperkalemia due to release of potassium from white blood cells during clotting. Author(s): Bronson WR, DeVita VT, Carbone PP, Cotlove E. Source: The New England Journal of Medicine. 1966 February 17; 274(7): 369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5216594&dopt=Abstract

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Qualitative changes of white blood cells and perinatal diagnosis of infection in highrisk preterm infants. Author(s): Amato M, Howald H, von Muralt G. Source: Padiatr Padol. 1988; 23(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3405612&dopt=Abstract

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Quantification of low frequency white blood cells expressing human cytomegalovirus antigen by image cytometry. Author(s): Jiwa NM, Mesker WE, Ploem-Zaaijer JJ, van Dorp W, The TH, Raap AK. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1994 May 1; 16(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8033736&dopt=Abstract

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Quantitative 99Tcm-HMPAO white blood cells and 67Ga scanning in rheumatoid arthritis. Author(s): Wang SJ, Kao CH, Chen DU, Lin MS, Yeh SH, Lan JL. Source: Nuclear Medicine Communications. 1991 June; 12(6): 551-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1866108&dopt=Abstract

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Quantitative PCR for counting residual white blood cells in blood products. Author(s): Legler TJ, Riggert J, Dove G, Kohler M. Source: Transfusion Science. 1999 April; 20(2): 107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10539113&dopt=Abstract

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Radiolabelled white blood cells in inflammatory bowel diseases. Author(s): Martin-Comin J. Source: Nuclear Medicine Communications. 2002 November; 23(11): 1039-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411830&dopt=Abstract

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Ras activation in normal white blood cells and childhood acute lymphoblastic leukemia. Author(s): von Lintig FC, Huvar I, Law P, Diccianni MB, Yu AL, Boss GR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 May; 6(5): 1804-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815901&dopt=Abstract

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Re: Selective in vitro labeling of white blood cells using 99mTc-labeled liposomes. Author(s): Laverman P, Boerman OC. Source: Nuclear Medicine and Biology. 2002 July; 29(5): 623. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088734&dopt=Abstract

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Recognition of white blood cells with an interactive morphometry system(T.A.S.). Author(s): Bins M, Gelsema E, van Montfort LH, Halie MR. Source: Microsc Acta Suppl. 1980; Suppl 4: 102-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6157076&dopt=Abstract

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Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics. Author(s): Gorski NP, Nouraldin H, Dube DM, Preffer FI, Dombkowski DM, Villa EM, Lewandrowski KB, Weiss RD, Hufford C, Laposata M. Source: Alcoholism, Clinical and Experimental Research. 1996 April; 20(2): 268-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8730217&dopt=Abstract

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Regulation of phosphoribosylpyrophosphate synthetase by endogenous purine and pyrimidine compounds and synthetic analogs in normal and leukemic white blood cells. Author(s): Danks MK, Scholar EM. Source: Biochemical Pharmacology. 1982 May 1; 31(9): 1687-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6285931&dopt=Abstract

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Rejoining of DNA single- and double-strand breaks in human white blood cells exposed to ionizing radiation. Author(s): Banath JP, Fushiki M, Olive PL. Source: International Journal of Radiation Biology. 1998 June; 73(6): 649-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9690683&dopt=Abstract

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Relationship between serum unconjugated bilirubin levels and the autofluorescence of white blood cells in neonatal jaundice. Author(s): Ozkan H, Akkoc N, Aydin A, Kavukcu, Olgun N, Irken G, Akyol F, Cevik NT. Source: Biology of the Neonate. 1995; 68(2): 100-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8534768&dopt=Abstract

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Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells. Author(s): Okpala I, Daniel Y, Haynes R, Odoemene D, Goldman J. Source: European Journal of Haematology. 2002 September; 69(3): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406006&dopt=Abstract

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Relevance of morphometric parameters for the classification of normal white blood cells. Author(s): Bins M, Landeweerd GH, Gelsema ES, van Montfort LH, Halie MR. Source: Clinical and Laboratory Haematology. 1982; 4(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7067375&dopt=Abstract

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Removal of white blood cells from gametocyte-, schizont-, trophozoite- and ring stages of Plasmodium falciparum. Author(s): Williamson J, Cover B. Source: Trans R Soc Trop Med Hyg. 1971; 65(4): 416. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4938404&dopt=Abstract

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Response of white blood cells to iodipamide ethyl ester particles. Author(s): Lauteala L, Kormano M, Violante MR. Source: Investigative Radiology. 1986 July; 21(7): 562-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3733383&dopt=Abstract

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Rheological behavior of white blood cells. Author(s): Mercuri M, Santambrogio L, Ciuffetti G, Lombardini R. Source: Stroke; a Journal of Cerebral Circulation. 1989 June; 20(6): 826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2728054&dopt=Abstract

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Rheological properties of white blood cells are changed in diabetic patients with microvascular complications. Author(s): Vermes I, Steinmetz ET, Zeyen LJ, van der Veen EA. Source: Diabetologia. 1987 June; 30(6): 434-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3678663&dopt=Abstract

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Role of white blood cells in filtration of blood cell suspensions. Author(s): Chien S, Schmalzer EA, Lee MM, Impelluso T, Skalak R. Source: Biorheology. 1983; 20(1): 11-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6871423&dopt=Abstract

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Scurvy presenting with cutaneous and articular signs and decrease in red and white blood cells. Author(s): Yalcin A, Ural AU, Beyan C, Tastan B, Demiriz M, Cetin T. Source: International Journal of Dermatology. 1996 December; 35(12): 879-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8970847&dopt=Abstract

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Selective in vitro labeling of white blood cells using 99mTc-labeled liposomes. Author(s): Andreopoulos D, Kasi LP, Asimacopoulos PJ, Jhingran SG, Cole W, Yang D, Kim EE. Source: Nuclear Medicine and Biology. 2002 February; 29(2): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11823123&dopt=Abstract

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Seminal white blood cells and recurrent abortion. Author(s): Hill JA, Anderson DJ, Polgar K, Abbott AF, Politch JA. Source: Human Reproduction (Oxford, England). 1994 June; 9(6): 1180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7962398&dopt=Abstract

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Seminal white blood cells in men with urethral tract infection. A monoclonal antibody study. Author(s): Barratt CL, Harrison PE, Robinson A, Kessopoulou E, Cooke ID. Source: British Journal of Urology. 1991 November; 68(5): 531-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1747731&dopt=Abstract

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Shortened telomere length in white blood cells of patients with IDDM. Author(s): Jeanclos E, Krolewski A, Skurnick J, Kimura M, Aviv H, Warram JH, Aviv A. Source: Diabetes. 1998 March; 47(3): 482-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519758&dopt=Abstract

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Significance of ascitic fluid white blood cells, pH, lactate, and other chemistry in immediate diagnosis of spontaneous bacterial peritonitis. Author(s): Neungton N, Kachintorn U, Chinapak O, Ong-Ajyooth S, Umpornsirirat S. Source: J Med Assoc Thai. 1994 May; 77(5): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869010&dopt=Abstract

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Significance of the low-density lipoprotein (LDL) receptor pathway for the in vitro accumulation of AD-32 incorporated into LDL in normal and leukemic white blood cells. Author(s): Vitols S, Gahrton G, Peterson C. Source: Cancer Treat Rep. 1984 March; 68(3): 515-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6322988&dopt=Abstract

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Simultaneous differentiation and quantitation of erythroblasts and white blood cells on a high throughput clinical haematology analyser. Author(s): Kim YR, Yee M, Metha S, Chupp V, Kendall R, Scott CS. Source: Clinical and Laboratory Haematology. 1998 February; 20(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9681207&dopt=Abstract

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Single cell gel electrophoresis assay: sensitivity of peripheral white blood cells in human population studies. Author(s): Sram RJ, Podrazilova K, Dejmek J, Mrackova G, Pilcik T. Source: Mutagenesis. 1998 January; 13(1): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9491403&dopt=Abstract

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Single-tube genomic DNA isolation from whole blood without pre-isolating white blood cells. Author(s): McIndoe RA, Linhardt MS, Hood L. Source: Biotechniques. 1995 July; 19(1): 30, 32-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669291&dopt=Abstract

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Skeletal uptake of indium 111-labeled white blood cells. Author(s): Abreu SH. Source: Semin Nucl Med. 1989 April; 19(2): 152-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2711199&dopt=Abstract

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Sodium-potassium pump activity in white blood cells from children with an increased risk of developing hypertension--The Odense Schoolchild Study. Author(s): Hansen HS, Nielsen JR, Pedersen KE, Johansen T, Klitgaard NA, Hyldebrandt N, Froberg K. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1993 February; 53(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8383874&dopt=Abstract

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Some cytochemical findings in the peripheral white blood cells in workers exposed to toluene. Author(s): Friborska A. Source: Folia Haematol Int Mag Klin Morphol Blutforsch. 1973; 99(2): 233-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4122967&dopt=Abstract

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Some factors influencing granulocytic colony formation in vitro by human white blood cells. Author(s): Heit W, Kern P, Kubanek B, Heimpel H. Source: Blood. 1974 October; 44(4): 511-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4415823&dopt=Abstract

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Some observations on the use of chemically labelled normal white blood cells as antigens in active immunization of leukaemia. Author(s): Sahasrabudhe MB, Madyastha KR, Prema S, Gollerkeri MP. Source: Biomedicine. 1974 January; 20(1): 31-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4526246&dopt=Abstract

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Studies on the use of chemically tagged normal white blood cells as antigens for producing specific immune response against human leukemic cells. Author(s): Sahasrabudhe MB, Prema S, Madyastha KR, Gollerkeri MP. Source: Indian Journal of Cancer. 1972 June; 9(2): 101-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4629010&dopt=Abstract

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Superoxide dismutase activities in serum and white blood cells of patients with some malignancies. Author(s): Abdel-Aziz AF, El-Naggar MM. Source: Cancer Letters. 1997 February 26; 113(1-2): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9065802&dopt=Abstract

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Suppression of tumor necrosis factor secretion from white blood cells by synthetic antisense phosphorothioate oligodeoxynucleotides. Author(s): Hu RH, Chu SH. Source: International Journal of Immunopharmacology. 2000 June; 22(6): 445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727755&dopt=Abstract

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Surface glycoproteins of human white blood cells. Analysis by surface labeling. Author(s): Andersson LC, Gahmberg CG. Source: Blood. 1978 July; 52(1): 57-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=306846&dopt=Abstract

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Survival of transfused donor white blood cells in HIV-infected recipients. Author(s): Kruskall MS, Lee TH, Assmann SF, Laycock M, Kalish LA, Lederman MM, Busch MP; Viral Activation Transfusion Study Group. Source: Blood. 2001 July 15; 98(2): 272-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435293&dopt=Abstract

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Tamoxifen does not form detectable DNA adducts in white blood cells of breast cancer patients. Author(s): Phillips DH, Hewer A, Grover PL, Poon GK, Carmichael PL. Source: Carcinogenesis. 1996 May; 17(5): 1149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8640926&dopt=Abstract

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Technetium-99m exametazime (99mTc-HMPAO)-labeled white blood cells: a high efficiency multidose procedure. Author(s): Ozker K, Collier BD, Hellman RS, Isitman AT, Uzum F, Steffel FG. Source: European Journal of Nuclear Medicine. 1995 February; 22(2): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7758507&dopt=Abstract

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Telomere length in human white blood cells remains constant with age and is shorter in breast cancer patients. Author(s): Levy T, Agoulnik I, Atkinson EN, Tong XW, Gause HM, Hasenburg A, Runnebaum IB, Stickeler E, Mobus VJ, Kaplan AL, Kieback DG. Source: Anticancer Res. 1998 May-June; 18(3A): 1345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673338&dopt=Abstract

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Thalidomide and the immune system. 3. Simultaneous up- and down-regulation of different integrin receptors on human white blood cells. Author(s): Nogueira AC, Neubert R, Helge H, Neubert D. Source: Life Sciences. 1994; 55(2): 77-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7516993&dopt=Abstract

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The biologic significance of white blood cells in semen. Author(s): Wolff H. Source: Fertility and Sterility. 1995 June; 63(6): 1143-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750580&dopt=Abstract

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The correlation between round cells and white blood cells in the semen. Author(s): Sigman M, Lopes L. Source: The Journal of Urology. 1993 May; 149(5 Pt 2): 1338-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8479031&dopt=Abstract

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The effect of cranberry juice on the presence of bacteria and white blood cells in the urine of elderly women. What is the role of bacterial adhesion? Author(s): Avorn J. Source: Advances in Experimental Medicine and Biology. 1996; 408: 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895791&dopt=Abstract

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The effect of prolonged perfusion with a membrane oxygenator (PPMO) on white blood cells. Author(s): Bergman P, Belboul A, Friberg LG, al-Khaja N, Mellgren G, Roberts D. Source: Perfusion. 1994 January; 9(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8161866&dopt=Abstract

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The effect of strenuous exercise, calorie deficiency and sleep deprivation on white blood cells, plasma immunoglobulins and cytokines. Author(s): Boyum A, Wiik P, Gustavsson E, Veiby OP, Reseland J, Haugen AH, Opstad PK. Source: Scandinavian Journal of Immunology. 1996 February; 43(2): 228-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8633203&dopt=Abstract

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The effects of Betamethasone on white blood cells during pregnancy with PPROM. Author(s): Diebel ND, Parsons MT, Spellacy WN. Source: Journal of Perinatal Medicine. 1998; 26(3): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9773380&dopt=Abstract

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The hydrolysis of fatty acid ethyl esters in low-density lipoproteins by red blood cells, white blood cells and platelets. Author(s): Saghir M, Blodget E, Laposata M. Source: Alcohol (Fayetteville, N.Y.). 1999 October; 19(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548161&dopt=Abstract

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The levels of TNF-alpha in cerebrospinal fluid and serum do not correlate with the counts of the white blood cells in acute phase of ischaemic stroke. Author(s): Zaremba J, Losy J. Source: Folia Morphol (Warsz). 2001; 60(2): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407149&dopt=Abstract

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The relationship between white blood cells and arterial disease. Author(s): Belch JJ. Source: Current Opinion in Lipidology. 1994 December; 5(6): 440-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7712049&dopt=Abstract

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The usefulness of in vivo gene expression investigations from peripheral white blood cells: a preliminary study. Author(s): Ember I, Kiss I, Raposa T. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1999 August; 8(4): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10493309&dopt=Abstract

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Therapeutic intervention of clinical sepsis with intravenous immunoglobulin, white blood cells and antibiotics. Author(s): Fischer GW, Weisman LE. Source: Scand J Infect Dis Suppl. 1990; 73: 17-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2128662&dopt=Abstract

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Time domain dielectric spectroscopy study of human cells. II. Normal and malignant white blood cells. Author(s): Polevaya Y, Ermolina I, Schlesinger M, Ginzburg BZ, Feldman Y. Source: Biochimica Et Biophysica Acta. 1999 July 15; 1419(2): 257-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10407076&dopt=Abstract

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Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study. Author(s): Schoemaker NE, Herben VM, de Jong LA, van Waardenburg RC, Pluim D, ten Bokkel Huinink WW, Beijnen JH, Schellens JH. Source: Anti-Cancer Drugs. 2002 January; 13(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914645&dopt=Abstract

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Transfusion in premature infants impairs production and/or release of red blood cells, white blood cells and platelets. Author(s): Frey B. Source: Journal of Paediatrics and Child Health. 2002 June; 38(3): 265-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047694&dopt=Abstract

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Treatment of rheumatoid arthritis by immunization with mononuclear white blood cells: results of a preliminary trial. Author(s): Smith JB, Fort JG. Source: The Journal of Rheumatology. 1996 February; 23(2): 220-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882022&dopt=Abstract

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Tumor necrosis factor-alpha and interleukin-6 release from white blood cells induced by different graft materials in vitro are affected by pentoxifylline and iloprost. Author(s): Swartbol P, Truedsson L, Parsson H, Norgren L. Source: Journal of Biomedical Materials Research. 1997 September 5; 36(3): 400-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9260111&dopt=Abstract

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Ultrastructural cytochemical localizations by back-scattered electron imaging of white blood cells. Author(s): Soligo D, de Harven E. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1981 September; 29(9): 1071-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6945361&dopt=Abstract

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Use of indium-111-labeled white blood cells in the diagnosis of diabetic foot infections. Author(s): Zeiger LS, Fox IM. Source: J Foot Surg. 1990 January-February; 29(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2319101&dopt=Abstract

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Use of technetium-tagged white blood cells in patients with Crohn's disease and ulcerative colitis: is differential diagnosis possible? Author(s): Charron M, del Rosario JF, Kocoshis S. Source: Pediatric Radiology. 1998 November; 28(11): 871-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799322&dopt=Abstract

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Utility of fever, white blood cells, and differential count in predicting bacterial infections in the elderly. Author(s): Wasserman M, Levinstein M, Keller E, Lee S, Yoshikawa TT. Source: Journal of the American Geriatrics Society. 1989 June; 37(6): 537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2715561&dopt=Abstract

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Vacuolated white blood cells in thalassemia major. Author(s): Duru F, Gumruk F, Gurgey A. Source: Turk J Pediatr. 1994 July-September; 36(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7974817&dopt=Abstract

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Viscosity of the packed red and white blood cells. Author(s): Dintenfass L. Source: Experimental and Molecular Pathology. 1965 December; 4(6): 597-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5850221&dopt=Abstract

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White blood cells 1: non-malignant disorders. Author(s): Stock W, Hoffman R. Source: Lancet. 2000 April 15; 355(9212): 1351-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776761&dopt=Abstract

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White blood cells and acute phase reactants in neonatal sepsis. Author(s): Philip AG. Source: Pediatrie. 1984 July-August; 39(5): 371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6084234&dopt=Abstract

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White blood cells and bone marrow in typhoid fever. Author(s): Mallouh AA, Sa'di AR. Source: The Pediatric Infectious Disease Journal. 1987 June; 6(6): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3615066&dopt=Abstract

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White blood cells and cerebrospinal fluid. Author(s): Scarano JJ. Source: Pediatrics. 1996 June; 97(6 Pt 1): 929. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657545&dopt=Abstract

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White blood cells and cortisol after sleep deprivation and recovery sleep in humans. Author(s): Heiser P, Dickhaus B, Schreiber W, Clement HW, Hasse C, Hennig J, Remschmidt H, Krieg JC, Wesemann W, Opper C. Source: European Archives of Psychiatry and Clinical Neuroscience. 2000; 250(1): 16-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738860&dopt=Abstract

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White blood cells and HIV-1 in semen from vasectomised seropositive men. Author(s): Anderson DJ, Politch JA, Martinez A, Van Voorhis BJ, Padian NS, O'Brien TR. Source: Lancet. 1991 August 31; 338(8766): 573-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1678827&dopt=Abstract

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White blood cells and platelets are integral to the hyperacute rejection of the pig heart by human blood. Author(s): Young VK, Kaspar-Konig W, Tew DN, Wallwork J, White DJ, Pierson RN 3rd. Source: Transplantation Proceedings. 1995 February; 27(1): 272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7879000&dopt=Abstract

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White blood cells and the diagnosis of alpha-glucosidase deficiency. Author(s): Dreyfus JC, Poenaru L. Source: Pediatric Research. 1980 April; 14(4 Pt 1): 342-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6769091&dopt=Abstract

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White blood cells and venous ulceration. Author(s): Thomas PR, Nash GB, Dormandy JA. Source: Bmj (Clinical Research Ed.). 1988 September 10; 297(6649): 685. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3155387&dopt=Abstract

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White blood cells as a novel mortality predictor in haemodialysis patients. Author(s): Reddan DN, Klassen PS, Szczech LA, Coladonato JA, O'Shea S, Owen WF Jr, Lowrie EG. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18(6): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748351&dopt=Abstract

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White blood cells as mediators of hyperviscosity-induced tissue damage in neutrophilic vascular reactions: therapy with pentoxifylline. Author(s): Ely H. Source: Journal of the American Academy of Dermatology. 1989 April; 20(4): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2715414&dopt=Abstract

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White blood cells cause oxidative damage to the fatty acid composition of phospholipids of human spermatozoa. Author(s): Zalata AA, Christophe AB, Depuydt CE, Schoonjans F, Comhaire FH. Source: International Journal of Andrology. 1998 June; 21(3): 154-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669199&dopt=Abstract

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White blood cells in infants with congenital toxoplasmosis: transient appearance of cALL antigen on reactive marrow lymphocytes. Author(s): Rajantie J, Siimes MA, Taskinen E, Lappalainen M, Koskiniemi M. Source: Scandinavian Journal of Infectious Diseases. 1992; 24(2): 227-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1386473&dopt=Abstract

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White blood cells in semen affect hyperactivation but not sperm membrane integrity in the head and tail regions. Author(s): Chan PJ, Su BC, Tredway DR, Whitney EA, Pang SC, Corselli J, Jacobson JD. Source: Fertility and Sterility. 1994 May; 61(5): 986-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8174744&dopt=Abstract

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White blood cells in the diagnosis of glycogenosis type II. Author(s): Poenaru L, Dreyfus JC. Source: Clinical Biochemistry. 1979 December; 12(6): 210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=43779&dopt=Abstract

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White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. Author(s): Korppi M, Heiskanen-Kosma T, Leinonen M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1997 May; 10(5): 1125-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9163657&dopt=Abstract

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White blood cells: what to do beyond measurement. Author(s): Saunders AM. Source: Blood Cells. 1980; 6(3): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7397392&dopt=Abstract

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Y chromatin frequency in white blood cells of newborn males. Author(s): Polakova H, Gencik A, Ferak V. Source: Journal of Perinatal Medicine. 1980; 8(3): 164-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7420261&dopt=Abstract

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CHAPTER 2. NUTRITION AND WHITE BLOOD CELLS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and white blood cells.

Finding Nutrition Studies on White Blood Cells 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.4 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 “white blood cells” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

A comparison of the NADPH oxidase in human sperm and white blood cells. Author(s): Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA. Source: Armstrong, J S Bivalacqua, T J Chamulitrat, W Sikka, S Hellstrom, W J Int-JAndrol. 2002 August; 25(4): 223-9 0105-6263

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Biological consequences of the heterogeneous irradiation of lymphocytes during technetium-99m hexamethylpropylene amine oxime white blood cell labelling. Author(s): Service de Biophysique, Faculte Saint-Antoine, Paris, France. Source: de Labriolle Vaylet, C Colas Linhart, N Sala Trepat, M Petiet, A Voisin, P Bok, B Eur-J-Nucl-Med. 1998 October; 25(10): 1423-8 0340-6997

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Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos. Author(s): Research Institute of Occupational Medicine, Ruhr University of Bochum, Germany. [email protected] Source: Marczynski, B Kraus, T Rozynek, P Schlosser, S Raithel, H J Baur, X Int-ArchOccup-Environ-Health. 2001 July; 74(5): 315-24 0340-0131

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Chicken lines differ in production of interferon-like activity by peripheral white blood cells stimulated with phytohemagglutinin. Author(s): USDA-Agricultural Research Service, Avian Disease and Oncology Laboratory, 3606 East Mount Hope Road, East Lansing, Michigan 48823, USA. [email protected] Source: Baco, L D Palmquistt, D Poult-Sci. 2002 November; 81(11): 1629-36 0032-5791

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DNA strand-breaks induced by the topoisomerase I inhibitor camptothecin in unstimulated human white blood cells. Author(s): Department of Cell Biology, Faculty of Biology, Avda. Reina Mercedes 6, 41012 Sevilla, Spain. [email protected] Source: Daza, P Torreblanca, J Garcia Herdugo, G Moreno, F J Cell-Biol-Int. 2002; 26(8): 707-13 1065-6995

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Effects of the butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the arylamines N-acetyltransferase activity in rat white blood cells. Author(s): Department of Urology, China Medical College Hospital, Taiwan, Republic of China. Source: Lu, H F Wu, H C Chang, W C Chung, J G Cytobios. 1999; 100(395): 159-69 00114529

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Expression and modulation of homologous restriction factor (HRF) on peripheral white blood cells. Author(s): Department of Dermatology and Pathology, University of California, San Diego School of Medicine 92103. Source: Sayama, K Zalman, L S Muller Eberhard, H J Gigli, I Trans-Assoc-AmPhysicians. 1988; 101270-81 0066-9458

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Influence of subchronic administration of oestrone-3-O-sulphamate on oestrone sulphatase activity in liver, spleen and white blood cells of ovariectomized rats. Author(s): Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany. [email protected] Source: Barth, A Romer, W Oettel, M Arch-Toxicol. 2000 September; 74(7): 366-71 03405761

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Linoleic acid levels in white blood cells, platelets, and serum of multiple sclerosis patients. Author(s): Department of Neurology, Worcester Memorial Hospital, MA 01605. Source: Fisher, M Johnson, M H Natale, A M Levine, P H Acta-Neurol-Scand. 1987 October; 76(4): 241-5 0001-6314

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Localization of DNA in ultrascopic nuclear appendages of polymorphonuclear white blood cells from patients with low serum B(12). Author(s): Department of Pathology, Harvard Medical School, and the James Homer Wright Laboratories of the Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [email protected] Source: Bunting, R W Selig, M K J-Histochem-Cytochem. 2002 October; 50(10): 1381-8 0022-1554

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Sample preparation and in situ hybridization techniques for automated molecular cytogenetic analysis of white blood cells. Author(s): Department of Cytochemistry and Cytometry, Leiden University, The Netherlands. Source: van de Rijke, F M Vrolijk, H Sloos, W Tanke, H J Raap, A K Cytometry. 1996 June 1; 24(2): 151-7 0196-4763

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The usefulness of in vivo gene expression investigations from peripheral white blood cells: a preliminary study. Author(s): Institute of Preventive Medicine, University Medical School of Pecs, Hungary. [email protected] Source: Ember, I Kiss, I Raposa, T Eur-J-Cancer-Prevolume 1999 August; 8(4): 331-4 0959-8278

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/

•

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

•

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

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•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Vitamins Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com

•

Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Integrative Medicine Communications; www.drkoop.com Retinol Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

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Selenium Source: Integrative Medicine Communications; www.drkoop.com Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html •

Food and Diet Source: Healthnotes, Inc.; www.healthnotes.com Kefir Source: Healthnotes, Inc.; www.healthnotes.com Lhassi Source: Healthnotes, Inc.; www.healthnotes.com Milk Source: Healthnotes, Inc.; www.healthnotes.com Natural Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Refined Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Shiitake Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,308,00.html Sugar Alcohols Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Cheese Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND WHITE BLOOD CELLS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to white blood cells. 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 white blood cells 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 “white blood cells” (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 white blood cells: •

(n-3) Polyunsaturated fatty acids promote activation-induced cell death in murine T lymphocytes. Author(s): Switzer KC, McMurray DN, Morris JS, Chapkin RS. Source: The Journal of Nutrition. 2003 February; 133(2): 496-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566490&dopt=Abstract

•

Noninvasive quantification of bowel inflammation through positron emission tomography imaging of 2-deoxy-2-[18F]fluoro-D-glucose-labeled white blood cells. Author(s): Pio BS, Byrne FR, Aranda R, Boulay G, Spicher K, Song MH, Birnbaumer L, Phelps ME, Czernin J, Silverman DH. Source: Molecular Imaging and Biology : Mib : the Official Publication of the Academy of Molecular Imaging. 2003 July-August; 5(4): 271-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499142&dopt=Abstract

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to white blood cells; 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 AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Allergies Alternative names: Hay Fever Source: Prima Communications, Inc.www.personalhealthzone.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bone Marrow Disorders Source: Integrative Medicine Communications; www.drkoop.com

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Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Common Cold/sore Throat Source: Healthnotes, Inc.; www.healthnotes.com Diverticular Disease Source: Integrative Medicine Communications; www.drkoop.com Epstein-Barr Virus Source: Integrative Medicine Communications; www.drkoop.com Fever of Unknown Origin Source: Integrative Medicine Communications; www.drkoop.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Leukemia Source: Integrative Medicine Communications; http://www.drkoop.com/ Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Myelofibrosis Source: Integrative Medicine Communications; www.drkoop.com

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Myeloproliferative Disorders Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Pharyngitis Source: Integrative Medicine Communications; www.drkoop.com Polycythemia Vera Source: Integrative Medicine Communications; www.drkoop.com Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Sore Throat Source: Integrative Medicine Communications; www.drkoop.com Thrombocytosis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Urinary Tract Infection Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Guided Imagery Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,699,00.html

•

Herbs and Supplements Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org AZT Source: Healthnotes, Inc.; www.healthnotes.com

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Benazepril Source: Healthnotes, Inc.; www.healthnotes.com Beta-glucan Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: Healthnotes, Inc.; www.healthnotes.com Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cranberry Source: Prima Communications, Inc.www.personalhealthzone.com Cranberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10019,00.html Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Alternative names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Source: Prima Communications, Inc.www.personalhealthzone.com Echinacea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Fumaric Acid Source: Healthnotes, Inc.; www.healthnotes.com Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: Healthnotes, Inc.; www.healthnotes.com

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Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Goldenseal Alternative names: Hydrastis canadensis Source: Integrative Medicine Communications; www.drkoop.com Herbal Decongestant Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,949,00.html Hydrastis Canadensis Source: Integrative Medicine Communications; www.drkoop.com Interferon Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: Healthnotes, Inc.; www.healthnotes.com Lindane Source: Healthnotes, Inc.; www.healthnotes.com Lisinopril Source: Healthnotes, Inc.; www.healthnotes.com Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Myrrh Alternative names: Commiphora molmol Source: Healthnotes, Inc.; www.healthnotes.com Noni Alternative names: Morinda citrifolia Source: Healthnotes, Inc.; www.healthnotes.com Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com

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Quinapril Source: Healthnotes, Inc.; www.healthnotes.com Ramipril Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. DISSERTATIONS ON WHITE BLOOD CELLS Overview In this chapter, we will give you a bibliography on recent dissertations relating to white blood cells. 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 “white blood cells” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on white blood cells, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on White Blood Cells 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 white blood cells. 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: •

Automatic White Blood Cell Differentiation by Park, Jaesang; PhD from University of Missouri - Columbia, 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3074435

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

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CHAPTER 5. CLINICAL TRIALS AND WHITE BLOOD CELLS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning white blood cells.

Recent Trials on White Blood Cells The following is a list of recent trials dedicated to white blood cells.5 Further information on a trial is available at the Web site indicated. •

Apheresis to Obtain Plasma or White Blood Cells for Laboratory Studies Condition(s): information

Leukopheresis;

Plasmapheresis;

MEDLINEplus

consumer

health

Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will collect blood plasma and white blood cells for laboratory research using a procedure called apheresis. Apheresis is a method of collecting larger quantities of certain blood components than can safely be collected through a simple blood draw. Patients 7 years of age and older with a parasitic infection or condition associated with a parasitic infection (i.e., elevated levels of IgE antibodies or of a type of white cell called eosinophils) who are currently enrolled in a NIH clinical research protocol may be eligible for this study. Relatives of patients and normal healthy volunteers will also be enrolled. Candidates will have a medical history, physical examination and blood tests. Individuals weighing less than 25 kilograms (55 pounds) may not participate. Participants will undergo one of the following two apheresis procedures: - Automated pheresis - Whole blood is drawn through a needle placed in an arm vein and circulated through a cell separator machine. The plasma (liquid part of the blood) and white cells are extracted, and the red cells are re-infused into the donor through a needle in the other arm. The procedure takes 1 to 2 hours. - Manual pheresis Whole blood is drawn through a needle placed in an arm vein and circulated through the cell separator machine. The red blood cells are separated from the rest of the blood 5

These are listed at www.ClinicalTrials.gov.

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and returned to the donor through the same needle. Usually only one needle stick is required and the procedure takes from 30 to 45 minutes. This method is used only in individuals who weigh less than 35 kg (77 pounds). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001349 •

Chemotherapy Followed by Donor White Blood Cells Plus Interleukin-2 in Treating Patients With Acute Myeloid or Lymphocytic Leukemia Condition(s): recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill leukemia cells. Treating donor white blood cells with interleukin-2 in the laboratory may help them kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy plus donor white blood cells treated with interleukin-2 in treating patients who have acute myeloid leukemia or acute lymphoid leukemia. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005802

•

Combination Chemotherapy Plus Infusion of White Blood Cells in Treating Patients With Hematologic Cancer Condition(s): childhood non-Hodgkin's lymphoma; myelodysplastic and myeloproliferative diseases

Leukemia;

Lymphoma;

Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. White blood cells from donors may be able to kill cancer cells in patients who have hematologic cancer that has recurred following bone marrow transplantation. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus infusion of donated white blood cells in treating patients who have hematologic cancer that has recurred after bone marrow transplantation. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003243

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•

Peripheral Stem Cell Transplantation Followed by White Blood Cell Infusion in Treating Patients With Hematologic Cancer Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Leukemia; Lymphoma; myelodysplastic and myeloproliferative diseases; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): University of Wisconsin Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Donor peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Donor white blood cells that have been treated in the laboratory may prevent this from happening. PURPOSE: Phase I trial to determine the effectiveness of donor peripheral stem cell transplantation followed by infusions of donor white blood cells in treating patients who have hematologic cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028041

•

Peripheral Stem Cell Transplantation, White Blood Cell Infusions, Chemotherapy, and Radiation Therapy in Treating Patients With Recurrent Metastatic Cervical or Vaginal Cancer Condition(s): Cervical Cancer; Vaginal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Donor peripheral stem cell transplantation and donor white blood cell infusions may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and cyclosporine may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of donor peripheral stem cell transplantation plus chemotherapy and total-body irradiation followed by donor white blood cell infusion in treating patients who have recurrent metastatic or locally advanced cancer of the cervix or vagina that is associated with human papillomavirus. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005941

•

Reduced Immunosuppressive Therapy With or Without Donor White Blood Cells in Treating Patients With Lymphoproliferative Disease After Organ Transplantation Condition(s): post-transplant lymphoproliferative disorder Study Status: This study is currently recruiting patients.

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Sponsor(s): University of Edinburg Purpose - Excerpt: RATIONALE: Some types of lymphoproliferative disease are associated with Epstein-Barr virus. Combining reduced immunosuppressive therapy with donor white blood cells that have been treated in the laboratory to kill cells infected with Epstein-Barr virus may be an effective treatment for lymphoproliferative disease. PURPOSE: Randomized phase III trial to compare the effectiveness of reducing immunosuppressive therapy with or without donor white blood cells in treating patients who have Epstein-Barr virus-associated lymphoproliferative disease after organ transplantation. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033475 •

Use of Bromodeoxyuridine to Study White Blood Cell Replication and Survival in HIV-Infected Patients Condition(s): HIV Infection; Acquired Immunodeficiency Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine how quickly white blood cells called CD4 lymphocytes reproduce and how long they live in people infected with HIV. It will do this using bromodeoxyuridine (BrDU), a compound that is structurally similar to thymidine, one of the building blocks of DNA. BrDU gets incorporated into DNA instead of thymidine, but it can only get into cells that are replicating. Therefore, measuring the proportion of cells with BrDU indicates how many cells are replicating. HIV-infected patients 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, chest X-ray, electrocardiogram (EKG) and blood tests. Participants will be given an infusion of BrDU through a catheter (thin plastic tube) placed in an arm vein. Blood will be drawn up to 4 times in the first 24 hours after the infusion. Additional samples will then be collected as often as daily for the first week, twice a week for the next 3 weeks and then weekly to monthly for up to 1 year. Some patients may undergo a tissue biopsy (removal of a small tissue sample from a lymph node, tonsil or colon) or computed tomography (CT) scans of the thymus (a small gland between the lungs that manufactures lymphocytes. Some patients will have a second infusion in order to examine changes in the rate of CD4 replication over time or following potent antiretroviral therapy. Patients will be followed in the clinic periodically for the first year and then will be seen in the clinic or contacted by telephone once a year for 4 more years. The results of this study may provide a better understanding of how HIV causes disease and how therapy affects the immune system. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001650

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

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CHAPTER 6. PATENTS ON WHITE BLOOD CELLS 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.6 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 “white blood cells” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on white blood cells, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on White Blood Cells By performing a patent search focusing on white blood cells, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 6Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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

Analysis of quiescent anticoagulated whole blood samples Inventor(s): Wardlaw; Stephen C. (Lyme, CT) Assignee(s): Levine; Robert A. (Guilford, CT), Wardlaw Partners, LP (Lyme, CT) Patent Number: 6,235,536 Date filed: February 12, 1999 Abstract: Formed constituents of a quiescent anticoagulated whole blood sample are optically or visually analyzed in a sample chamber which has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls of the chamber is transparent so that the blood sample constituents can be observed. The chamber's varying thickness produces a first lesser thickness region in the chamber wherein a quiescent monolayer of red blood cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells in the sample are unable to enter the aforesaid lesser thickness region of the chamber. The red cells which reside in the greater thickness regions will agglomerate to form rouleaux and lacunea. The exact thickness of the chamber at any particular location in the chamber can be predetermined, or can be determined in situ as the sample is being analyzed. By admixing certain dyes with the blood sample, various characteristics and other information can be derived from the various formed constituents in the sample by means of a scanning instrument which is able to measure various color and other signals emitted from the sample at various locations within the chamber, or by means of visual examination of the sample in the chamber. The thickness of the lacunae areas of the sample can be calculated by the instrument as a function of signal emission strength from the dyes or stains. The emissions can be the result of sample fluorescence or can be the result of signal density through the sample. Particle volumes can be measured as a function of signal emission suppression caused by the particles. Erythrocyte sedimentation rates (ESR) can also be derived from a blood sample disposed in the sampling chamber. Excerpt(s): This invention relates to an apparatus and method for analyzing a quiescent sample of anticoagulated whole blood. More particularly, this invention relates to an apparatus and method for analyzing the blood sample in a quiescent state, without the need for fluid streams passing through the blood sample analysis apparatus during the analytic process. Blood constituent counts per unit volume of sample; blood constituent volumes; hematocrit; hemoglobin measurements; close approximation of erythrocyte sedimentation rates; and blood constituent type identification can all be performed using the apparatus and method of this invention. Recent advances in biological fluid analysis, and in particular, analytical hematology have increased the quantity and quality of information available from a patients blood sample. As a result, the medical community's interest in using patients blood samples as a diagnostic tool has also increased, and the most commonly performed test performed on whole, anticoagulated blood is the complete blood count, or CBC, which is a suite of tests which are considered to include measurements of the hematocrit (Hct), hemoglobin (Hgb), red blood cell count (RBC). white blood cell count (WBC) and platelet count (Pit), red blood cell metrics such as the mean cell volume (MCV) and others, as well as the leukocyte differential count (LDC or "Diff") which is the classification of the types of white blood cells present. Compared to any other laboratory test, it is a peculiar characteristic of the

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CBC, that any instrument or method which performs it must do four different types of analyses. First, the general physical properties of the sample, namely the hematocrit and various cell or particle counts must be analyzed using quantitative methods relating to the entire sample. In conventional instrumentation and methods, this requires accurate sample metering and dilution, followed by specialized measurement apparatus. Secondly, a specific chemical property of the sample, namely the hemoglobin concentration, must be measured, usually by quantitative chemical means. Thirdly, the instrument must measure quantitative aspects of the individual cells, which usually involves providing a high dilution of the sample with a subsequent passage of the diluted material through a flow cell which measures the cells using electrical or optical means. Fourthly, qualitative measurements are used to classify the percentage of the total white blood cells which are composed of specific sub-populations. The number of sub-populations depends upon the sophistication of the instrument involved, which may be as little as two or more than seven classifications. Historically, the different aspects of the CBC have been performed using separate methods. For example, the LDC portion of a CBC was traditionally performed by smearing a small amount of undiluted blood on a slide, staining the dried fixed film and examining the smear under a microscope. Reasonable results can be gained from such a smear, but the accuracy and reliability of the data depends largely on the technician's experience and technique. In addition, the use of blood smears is labor intensive and cost prohibitive, and is therefore generally not favored for commercial applications. Another method uses electrical impedance or optical flow cytometry. Flow cytometry involves passing a diluted blood sample through a small vessel wherein electrical impedance or optical sensors can evaluate the constituent cells as they pass serially through the vessel. The same apparatus may also be used to simultaneously enumerate and provide cell metric data. To evaluate WBC's and/or platelets, the blood sample must be diluted, and the sample must be treated to mitigate the overwhelming number of the RBC's relative to the WBC's and the platelets. Although more expedient and consistent than the above described smear methods, flow cytometry also possesses several disadvantages. One disadvantage of flow cytometry is the plumbing and fluid controls that are necessary for controlling the flow rate of the diluted blood sample past the sensors, The plumbing in current flow cytometers can, and often does, leak, thus potentially compromising the accuracy and the safety of the equipment. Another disadvantage of many current flow cytometers relates to the accuracy of the internal fluid flow controls and automated dilution equipment. The accuracy of the flow cytometer depends upon the accuracy of the fluid flow controls and the sample dilution equipment, and their ability to remain accurately calibrated. Flow controls and dilution equipment require periodic recalibration. The need for recalibration illustrates the potential for inaccurate results and the undesirable operating costs that exist with many presently available flow cytometers. Web site: http://www.delphion.com/details?pn=US06235536__ •

Blood processing method and apparatus using a centrifugation bowl with filter core Inventor(s): Pages; Etienne (Segny, FR) Assignee(s): Haemonetics Corporation (Braintree, MA) Patent Number: 6,464,624 Date filed: June 12, 2001 Abstract: The invention is directed to blood processing method and apparatus utilizing a centrifugation bowl with a filter core disposed within the bowl. The centrifugation

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bowl includes a rotating bowl body defining an enclosed separation chamber. A generally cylindrical filter core is disposed inside the separation chamber. The filter core includes a filter membrane that is sized to block at least white blood cells, but to allow plasma to pass through. The filter core is generally arranged within the separation chamber such that plasma is forced to pass through the filter core before being removed from the centrifugation bowl. The addition of the filter core provides an efficient, lowcost method for recovering a "purer" plasma fraction from a donor. Excerpt(s): The invention relates to blood processing apparatus having centrifugation bowls for separating blood and other similar fluids. More specifically, the present invention relates to such apparatus with a centrifugation bowl having a rotating filter core for use in recovering a plasma fraction from whole blood. Human blood predominantly includes three types of specialized cells (i.e., red blood cells, white blood cells, and platelets) that are suspended in a complex aqueous solution of proteins and other chemicals called plasma. Although in the past blood transfusions have used whole blood, the current trend is to collect and transfuse only those blood components of fractions required by a particular patient. This approach preserves the available blood supply and in many cases is better for the patient, since the patient is not exposed to unnecessary blood components, especially white blood cells, which can transmit pathogens. Two of the more common blood fractions used in transfusions are red blood cells and plasma. Plasma transfusions, in particular, are often used to replenish depleted coagulation factors. Indeed, in the United States alone, approximately 2 million plasma units are transfused each year. Collected plasma is also pooled for fractionation into its constituent components, including proteins, such as Factor VIII, albumin, immune serum globulin, etc. Individual blood components, including plasma, can be obtained from units of previously collected whole blood through "bag" centrifugation. With this method, a unit of anti-coagulated whole blood contained in a plastic bag is placed into a lab centrifuge and spun at very high speed, subjecting the blood to many times the force of gravity. This causes the various blood components to separate into layers according to their densities. In particular, the more dense components, such as red blood cells, separate from the less dense components, such as white blood cells and plasma. Each of the blood components may then be expressed from the bag and individually collected. Web site: http://www.delphion.com/details?pn=US06464624__ •

Cell growth regulator Inventor(s): Fishman; Pnina (Herzliya, IL), Raouf; Guirguis (Rockville, MD) Assignee(s): Can-Fite Technologies Ltd. (Tel-Aviv, IL) Patent Number: 5,962,331 Date filed: September 21, 1995 Abstract: A substance secreted or shed by muscle cells and white blood cells is disclosed. This novel substance is active in inhibiting proliferation of tumor cells and proliferation of stimulated lymphocytes. The substance does not inhibit proliferation of normal cells. This substance is used in accordance with the invention for treatment or prevention of cancer and the level of said substance in a body fluid or in a fluid conditioned by the growth therein of cells withdrawn from the individual, is used for the diagnosis of cancer or the level of risk of the individual of developing cancer. Excerpt(s): The present invention is generally in the field of human and veterinary medicine and concerns novel substances which effect growth and proliferation of cells.

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The present invention is also concerned with uses of the substances in prevention or therapy of diseases. The invention further concerns a method of diagnosis of diseases or screening for individuals which are prone to or which have a predisposition to develop a disease. The above terms should be construed and understood with reference also to the description below. There is a heavy body of research involved the discovery, characterization, biological testing and clinical development of EGRs known as "cytokines". All cytokines discovered to date are proteinaceous substances having a molecular weight in the range of several thousand Daltons to several tens of thousands of Daltons. Cytokines, although having different source and target cells and have different mode of activities, share a common denominator in that all are proteinaceous substances. Web site: http://www.delphion.com/details?pn=US05962331__ •

Compositions of highly-purified natural mixtures of type I interferon derived from leukocytes and methods Inventor(s): Feldman; Stephen B. (Passaic, NJ), Hartman; Hipolito (Miami, FL), Kappelman; James (Worcester, MA), McCabe; Mead M. (Miami, FL), Morris; Joseph P. (Arnold, MD), Nguyen; Duy (Madison, WI), Potter; Michael D. (Acton, MA), Ziai; Reza (Weston, FL) Assignee(s): Viragen, Inc. (Plantation, FL) Patent Number: 6,350,589 Date filed: December 31, 1998 Abstract: This invention relates to methods for isolating highly-purified mixtures of natural type I interferons from white blood cells. The invention also relates to highlypurified mixtures of natural type I interferons which resemble natural type I interferon in that it includes 9 subtypes, i.e., alpha-1, alpha-2, alpha-5, alpha-7, alpha-8, alpha-10, alpha-14, alpha-21 and omega, giving rise to possibly 20 molecular species, including alpha-1a, alpha-1new, alpha-2a, alpha-2b, alpha-2c, alpha-5, alpha-5LG, alpha-7, alpha8a, alpha-8c, alpha-10a, alpha-14a, alpha14-b, alpha 14-c, alpha-14LG, alpha-21a, alpha21b, alpha-21c, omega and omega LG. Excerpt(s): This invention relates to methods for isolating highly-purified mixtures of natural type I interferons from white blood cells, and particularly human white blood cells. The invention also relates to highly-purified mixtures of natural type I interferons which resemble natural type I interferon in that it includes 9 subtypes, i.e., alpha-1, alpha-2, alpha-5, alpha-7, alpha-8, alpha-10, alpha-14, alpha-21 and omega, giving rise to possibly 20 molecular species, including alpha-1a, alpha-1new, alpha-2a, alpha-2b, alpha-2c, alpha-5, alpha-5LG, alpha-7, alpha-8a, alpha-8c, alpha-10a, alpha-14a, alphal 14-b, alpha 14-c, alpha-14LG, alpha-21a, alpha-21b, alpha-21c, omega and omega LG. The interferons are a family of proinflammatory cytokines important in mediating nonspecific host defense. While of critical importance in initiating anti-viral immunity, the family also acts as a potent initiator of cell growth and differentiation. Type I interferon is a designation for a family of related interferons that can include multiple subtypes of alpha interferon, beta interferon, omega interferons, and in some species the related trophoblast tau interferon. The proteins are structurally similar, share common receptors, have common biological activities and may share a common genetic locus. The type I interferons are believed to have three major functions. First, they inhibit viral replication by activating cellular genes that inhibit protein synthesis, thus contributing to the suppression of viral replication. Second, they downregulate the proliferation of

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specific cell types, a characteristic applied to the treatment of certain cancers. Finally, they have an immunomodulatory effect, which can influence the nature of the immune response (i.e. cellular or humoral) while activating innate components such as NK cells or monocytes. Web site: http://www.delphion.com/details?pn=US06350589__ •

Control system for the spillover collection of sparse components such as mononuclear cells in a centrifuge apparatus Inventor(s): Felt; Thomas J. (Boulder, CO), Hlavinka; Dennis (Arvada, CO) Assignee(s): Cobe Laboratories, Inc. (Lakewood, CO) Patent Number: 5,876,321 Date filed: June 9, 1997 Abstract: A centrifuge apparatus is used for collecting white blood cells (WBC), primarily mononuclear cells, from whole blood stratified into layers. A thin mononuclear (MNC) layer is formed at the interface of red blood cells and plasma. A barrier is positioned in the separation vessel of the centrifuge at a location to intercept the thin layer. MNC fluid is allowed to pool behind the barrier before collection is started. To collect the MNC pool, the stratified red blood cell layer is raised from below the interface level by slowing or reversing flow in the RBC exit line thereby causing the MNC pool to spill over the barrier into a well in which a collect line is positioned. Collection ceases when a desired percentage of the pool is removed and the normal position of the interface is re-established; thereafter the pool builds again. By raising the MNC pool from below, improvements in purity and collect volume are achieved. The collection procedure can be useful for harvesting granulocytes and, in general, any sparse stratified component of a centrifuged solution where the sparse component is layered between more dense and less dense strata. Excerpt(s): Centrifugation is a technique used to process whole blood in order to separate the blood into its various components. To reduce personal contact with blood products and reduce cross-contamination between different blood sources, the centrifugal apparatus can be fitted with a disposable plastic vessel through which the blood is circulated. The vessel is fitted into a centrifuge fixture that is driven by a motor. An exemplary vessel is a circumferential separation channel having several outlets positioned at different radial positions within the channel in order to remove blood components which have been separated by the centrifuge into stratified layers of differing density. Red blood cells (RBC) being the most dense of the components are stratified within the channel at the most radially outward location whereas the stratified layer of plasma is the least dense component and therefore the most radially inward layer. A relatively thin layer called the buffy coat contains white blood cells and platelets and is located between the red blood cell layer and the plasma layer. Within the buffy coat the platelets are stratified toward the plasma while the white blood cells are stratified toward the red blood cells. Depending on centrifuge speed, platelets may also be dispersed within the plasma. The disposable plastic vessel which is fitted into a rotating fixture within the centrifuge is connected to the blood source and to collection reservoirs through a disposable tubing set. In that manner, the centrifuge equipment itself is kept out of contact with blood and the disposable tubing set and separation channel are discarded after one procedure. The source of blood can be whole blood flowing directly from a donor or patient, or it can be previously donated bone marrow or blood. Blood components may be collected from a patient, stored and perhaps frozen,

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and reinfused into the patient days or even years later. The mononuclear cell portion of white blood cells is sometimes collected, stored in the above manner, and reinfused into the patient for the treatment of diseases such as cancer. There are obvious advantages to returning blood components from the patient's own blood rather than using the blood of a donor. It is generally agreed that the safest blood a person can receive is his or her own blood (autologous blood). The use of autologous blood reduces the risk of exposure to transfusion transmitted disease and febrile/allergic transfusion reactions. To accomplish the collection of white blood cells (WBC), an apheresis system has been developed for harvesting them from the buffy coat. In particular, the mononuclear cell (MNC) portion of WBCs are harvested including lymphocytes, monocytes, progenitor cells, and stem cells. In this document the designations WBCs and MNCs are usually used interchangeably. Efficient equipment for collecting MNCs is described in U.S. Pat. No. 4,647,279. However, even with efficient equipment, the collection of mononuclear cells is difficult since they make up only a small fraction of the total blood volume. For a patient of normal size with a normal MNC count, the total volume of MNCs may be about 1.5 milliliters, that is about 0.03% of the total blood volume. As a consequence, when whole blood is centrifuged, only a very thin MNC layer appears between the red blood cell and plasma layers. Web site: http://www.delphion.com/details?pn=US05876321__ •

Determination of white blood cell differential and reticulocyte counts Inventor(s): Levine; Robert A. (Guilford, CT), Rodriguez; Rodolfo R. (Cary, NC), Wardlaw; Stephen C. (Old Saybrook, CT) Assignee(s): Belton Dickinson & Co. (Franklin Lakes, NJ) Patent Number: 6,350,613 Date filed: February 18, 1999 Abstract: Target nucleated cells, and target cells containing remnant ribosomal material, which are present in a quiescent anticoagulated whole blood sample are optically detected, enumerated, and analyzed in a sample chamber that has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls of the chamber is transparent so that the blood sample can be observed. The chamber's varying thickness produces a first lesser thickness region in the chamber wherein individual red cells and quiescent monolayers of red cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells and nucleated red blood cells present in the sample will reside in greater thickness regions of the chamber, and non-nucleated red cells which reside in such greater thickness regions will agglomerate to form rouleaux. By admixing fluorescent dyes with the blood sample, target cells in the sample can be enumerated and differentiated by means of a scanning instrument which is able to measure different wave length color signals emitted from the target cells in the sample, and differentiate the target cells one from another by reason of the nature of the emitted color signals. Excerpt(s): This invention relates to an apparatus and method for analyzing a quiescent sample of anticoagulated whole blood. More particularly, this invention relates to an apparatus and method for analyzing the blood sample in a quiescent state in order to provide a white blood cell differential count, a reticulocyte count analysis, an enumeration of nucleated red blood cells, and the ability to detect abnormal nucleated circulating cells, such as cancer cells, which are rare events. Recent advances in

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analytical hematology have increased the quantity and quality of information available from a patient's blood sample. As a result, the medical community's interest in using patients' blood samples as a diagnostic tool has also increased, with the most commonly performed test performed on anticoagulated whole blood being the complete blood count, or CBC, which is a suite of tests which may include, in addition to the enumeration of the cellular components and platelets, red blood cell metrics; reticulocyte counts; and the leukocyte differential count (LDC or "Diff") which is the classification of the types of white blood cells present in the blood sample. The general physical properties of the sample, namely various cell or counts must be analyzed using quantitative methods relating to the entire sample. In conventional instrumentation and methods, this requires accurate sample metering and dilution, followed by specialized measurement apparatus. Additionally, the instrument must measure quantitative aspects of the individual cells, which usually involves providing a high dilution of the sample with a subsequent passage of the diluted material through a flow cell which measures the cells using electrical or optical means. Still further, qualitative measurements are used to classify the percentage of the total white blood cells which are composed of specific sub populations. The number of sub-populations depends upon the sophistication of the instrument involved, which may be as little as two or more than seven classifications. Historically, the differential aspects of the CBC have been performed using separate methods from those used for enumeration. For example, the LDC portion of a CBC was traditionally performed by smearing a small amount of undiluted, blood on a slide, staining the dried, fixed smear, and examining the smear under a microscope. Reasonable results can be gained from such a smear, but the accuracy and reliability of the data depends largely on the technician's experience and technique. One problem with such smears is that the cells must be killed and fixed, and this precludes many types of supravital stains and analyses whose results depend upon the living cell, such as some cytochemical analyses. In addition, the use of blood smears is labor intensive and cost prohibitive, and is therefore generally not favored for commercial applications. Web site: http://www.delphion.com/details?pn=US06350613__ •

Efficient method of detecting an infectious agent in blood Inventor(s): Goodwin; Mark A. (160 Lawrenceville Ave., Jefferson, GA 30549), Novak; Renata (180 Cross Creek Pl., Aptartment #4, Athens, GA 30605), Ragland; William L. (107 Sena Dr., Athens, GA 30605) Assignee(s): none reported Patent Number: 6,127,115 Date filed: November 14, 1996 Abstract: The present invention provides a method for detecting the presence of a predetermined infectious agent in a human or animal subject comprising obtaining a preselected portion of a whole blood sample containing at least one intact blood cell from the subject and detecting the presence of a nucleic acid from the predetermined infectious agent in the intact blood cell by nucleic acid hybridization. The preselected portion of the blood sample can include any portion which contains at least one intact blood cell, for example a peripheral blood smear or cytospin buffy coat preparation. The intact blood cell can be any blood cell including, but not limited to white blood cells and red blood cells. In one embodiment, the blood cell is a lymphocyte.

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Excerpt(s): The present invention relates to the field of rapid detection and diagnosis of an infectious agents in a subject utilizing a nucleic acid amplification technique performed directly on intact blood cells in a blood sample obtained from the subject. Detection of nucleic acids has an important role in diagnosis of a variety of diseases. The conventional molecular techniques for detection of nucleic acids are usually time consuming and require laborious preparation of samples, including nucleic acid extraction. The use of those harsh procedures results in destruction of cellular morphology, which is a great disadvantage in cases when cellular localization of specific sequences is of particular interest. Chicken anemia virus (CAV), formerly called chicken anemia agent (CAA), was first isolated by Yuasa et al.sup.1 and its viral particles were found to contain circular single-stranded DNA.sup.2,3. CAV causes severe aplastic anemia in chickens.sup.1,4,5, depletion of lymphoid organs, subcutaneous and intramuscular hemorrhages, and destruction of erythroblastoid cells in bone marrow.sup.6,7,8. Immune suppression caused by CAV infection is among the most important aspects of the disease.sup.9,10,11,12. In the field, CAV causes more serious problems when associated with other viruses.sup.13,14,15,16,17. Web site: http://www.delphion.com/details?pn=US06127115__ •

Incorporation of contextual information in object identification Inventor(s): Abu-Mostafa; Yaser (Pasadena, CA), Kasdan; Harvey (Sherman Oaks, CA), Sill; Joseph (Pasadena, CA), Song; Xubo (Portland, OR) Assignee(s): California Institute of Technology (Pasadena, CA) Patent Number: 6,594,586 Date filed: October 28, 1998 Abstract: Analysis of white blood cells is carried out by first analyzing the sample using image processing to obtain a no-context estimate of each cell's content. Then, a post processing operation is carried out to refine the estimate to include information about neighboring white blood cells. The estimate is refined to take into account the identity of the neighboring cells. Excerpt(s): The invention relates to techniques of identifying and classifying objects. More specifically, the present system describes using contextual information to improve statistical accuracy. A common assumption made in the field of machine learning is that the examples are drawn independently from some joint input-output distribution. Classical statistics begins with an assumption of a population distribution. Tiat population distribution describes how some attribute varies over a set of entities. The goal is to obtain information about the population distribution by sampling or by some other real world technique. It is often impractical to evaluate the parameters exactly. Therefore, one attempts, using the techniques of statistics, to obtain as much information as one can based on experimental evidence. Then all of the parameters can be viewed a coordinates of a single vector often called x. The value of x is fixed, but there is uncertainty about its value. Web site: http://www.delphion.com/details?pn=US06594586__

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Method and apparatus for reflected imaging analysis Inventor(s): Groner; Warren (Great Neck, NY), Nadeau; Richard G. (North East, MD) Assignee(s): Cytometrics, Inc. (Philadelphia, PA) Patent Number: 6,104,939 Date filed: January 25, 1999 Abstract: Method and apparatus for reflected imaging analysis. Reflected imaging is used to perform non-invasive, in vivo analysis of a subject's vascular system. A raw reflected image (110) is normalized with respect to the background to form a corrected reflected image (120). An analysis image (130) is segmented from the corrected reflected image to include a scene of interest for analysis. The method and apparatus can be used to determine such characteristics as the hemoglobin concentration per unit volume of blood, the number of white blood cells per unit volume of blood, a mean cell volume, the number of platelets per unit volume of blood, and the hematocrit. Cross-polarizers can be used to improve visualization of the reflected image. Excerpt(s): The present invention is related to reflected light analysis. More particularly, the present invention is related to the use of reflected spectral imaging to perform noninvasive analysis of a subject's vascular system. The present invention is also related to the use of cross-polarizers in reflected spectral imaging analysis. Widely accepted medical school doctrine teaches that the complete blood count including the white blood cell differential (CBC+Diff) is one of the best tests to assess a patient's overall health. With it, a physician can detect or diagnose anemia, infection, blood loss, acute and chronic diseases, allergies, and other conditions. CBC+Diff analyses provide comprehensive information on constituents in blood, including the number of red cells, the hematocrit, the hemoglobin concentration, and indices that portray the size, shape, and oxygen-carrying characteristics of the entire red blood cell (RBC) population. The CBC+Diff also includes the number and types of white blood cells and the number of platelets. The CBC+Diff is one of the most frequently requested diagnostic tests with about two billion done in the United States per year. A conventional CBC+Diff test is done in an "invasive" manner in which a sample of venous blood is drawn from a patient through a needle, and submitted to a laboratory for analysis. For example, a phlebotomist (an individual specially trained in drawing blood) collects a sample of venous blood into a tube containing an anticoagulant to prevent the blood from clotting. The sample is then sent to a hematology laboratory to be processed, typically on automated, multiparameter analytical instruments, such as those manufactured by Coulter Diagnostics of Miami, Fla. The CBC+Diff test results are returned to the requesting physician, typically on the next day. Web site: http://www.delphion.com/details?pn=US06104939__

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Method for concentrating white cells from whole blood by adding a red cell sedimentation reagent to whole anticoagulated blood Inventor(s): Coelho; Philip Henry (El Dorado Hills, CA), Rubinstein; Pablo (New Rochelle, NY), Stevens; Cladd E. (New York, NY) Assignee(s): New York Blood Center, Inc. (New York, NY) Patent Number: 5,789,147 Date filed: December 5, 1994

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Abstract: A therapeutic product formed from a high concentration of white blood cells having a high degree of cell viability. The white blood cells are sequestered from their normal population presence in whole blood by placing the blood into a container and preventing coagulation of the blood, separating the blood into two components, one of which is extremely rich in white blood cells through the use of a reagent and centrifugation, sequestering the white cell concentration, and freezing the white cells. Excerpt(s): The following invention is directed generally to the therapeutic utilization of white blood cells, a technique for sequestering the white blood cells by causing them to coalesce in a population density greater than they normally occur in nature, and a method for causing an enriched concentration in conjunction with an array of bags oriented in a set that facilitates both the concentration process and a method for preserving the white blood cells. It is now recognized that placenta/umbilical cord blood (PB) contains large numbers of hematopoietic stem and progenitor cells that endow PB with extraordinary therapeutic capabilities in the reconstitution of bone marrow damaged as a result of inherited diseases, accidents or medical procedures. As in the case of ordinary collection of bone marrow for transplantation, PB contains immune cells potentially capable of mounting specific responses against the recipients of such transplants, but in contrast to adult immunological cells, those in PB display a lower, perhaps much lower tendency to produce damaging immune responses against the recipient. The clinical syndrome produced by the immuno responses of the graft against the recipient's cells and tissues is designated "Graft versus Host Disease" (GVHD). In the typical clinical situation, the recipient's own immune response against the graft is abrogated by drugs and irradiation treatments designed to reduce or eliminate the immunological and other hematopoietic cells and thus avoid the host versus graft immune reaction that would cause rejection of the graft. It has been proven that the principal targets of these Graft versus Host and Host versus Graft immune reactions are antigens encoded by the genes of the HLA (Human Leukocyte Antigen) system and that successful outcomes of bone marrow transplants are dependent on the sharing of HLA antigens by donor and recipient. Sibling donors who have inherited the same paternal and maternal HLA genes present in the recipient are HLA-identical and thus, optimal from this viewpoint. Patients lacking such HLA-identical sibling donors must receive transplants from more distant relatives or from unrelated donors. Because the HLA system includes several discrete genes each of which displays an extremely large number of antigenically different variants in the population, such distant relativedonor or unrelated-donor transplants must be expected to contain a variable number of HLA incompatibilities unless they are selected from among potential donors by identifying the specific variants present in each and choosing donors whose HLA antigens match those of the recipient. To perform this selection with significant probability of success, it is necessary to have access to large panels of potential donors whose HLA antigens are known. In the case of unrelated donor PB, this requires establishing a bank of frozen HLA-typed units collected from random placentas. Heretofore, the most widely accepted method for freezing PB consisted of adding to the whole PB unit an equal volume of a cryopreservative solution, with the double disadvantage that the volume of each cryopreserved unit becomes very large and that a relatively large amount of possibly deleterious cryopreservative is eventually administered to the recipients of such PB units. Administration of cryoprotectant and hemoglobin from erythrocytes destroyed by using a freezing and thawing method designed to protect the stem and progenitor cells but not the erythrocytes may have toxic effects generally and especially on specific organs such as the kidney of the recipient. In addition, there is the logistical consequence that a large number of freezers would be needed to contain useful numbers of the large volume frozen units in reserve,

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with the attending increase in up-front and running costs. The applicants have developed a practical method that allows a substantial reduction of the volume of PB Units by eliminating the unneeded mature red blood cells and an equivalent volume of plasma. This submission describes this method and a specially designed set of plastic bags and connecting tubes intended to facilitate the accomplishment of the desired concentration of the needed stem cells and progenitor cells with minimal manipulation and risk of contamination. Essentially, this method will allow an experimental, time consuming laboratory process to become a routine procedure in blood banks. The following submission reflects the state of the art of which applicant is aware insofar as these documents appear germane to the patent process. However, it is respectfully stipulated that none of these patents teach singly nor render obvious when considered in any conceivable combination the nexus of the instant invention as set forth hereinafter. Web site: http://www.delphion.com/details?pn=US05789147__ •

Method for determination of leukocytes and hemoglobin concentration in blood Inventor(s): Li; Yi (Miami, FL), Raynor; Robert H. (Cooper City, FL), Young; Carole (Miami, FL) Assignee(s): Coulter International Corp. (Miami, FL) Patent Number: 5,882,933 Date filed: July 25, 1997 Abstract: A method is provided for differentiating leukocyte subpopulations, immunophenotyping of lymphocytes and counting white blood cells. The method preserves leukocyte morphology and surface markers without using fixatives. In addition, the method finds utility in determination of hemoglobin concentration without using cyanide. The stable hemoglobin chromogen formed is measured at approximately 540 nm. Excerpt(s): The present invention relates to a method to enable a determination of leukocyte subpopulations in a blood cell sample by means of suitable electronic instrumentation. In addition, the present invention relates to a determination of hemoglobin concentration in said blood sample. Analysis of leukocyte subpopulations from whole blood samples is an integral and essential part of diagnostic procedures regarding a multiplicity of pathologies. The ability to analyze the major subpopulations of leukocytes in an automated manner is essential for a rapid diagnosis of a single blood sample and for the rapid processing of many samples at once. In addition, the determination of hemoglobin concentration provides useful diagnostic information about the health of a patient. Traditional diagnosis of blood samples involves the smearing of a blood sample on a microscope slide, followed by manual visual analysis of the individual slide. This approach is extremely time-consuming as well as being subjective to the interpretation of the individual analyzing the slide. These factors have led to the development of automated leukocyte analysis utilizing flow cytometry. In automated leukocyte analysis using hematology instruments, the red blood cells are lysed which enables the differentiation of the leukocytes and determination of hemoglobin concentration. Web site: http://www.delphion.com/details?pn=US05882933__

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Method for diagnosing autoimmune diseases Inventor(s): Medenica; Rajko D. (Hilton Head Island, SC) Assignee(s): His Excellency Ghassan I. Shaker (London, GB2) Patent Number: 5,846,758 Date filed: November 30, 1995 Abstract: A method for diagnosing autoimmune disease in mammals, including humans, is described. A blood sample is collected from a subject, and mononuclear white blood cells separated therefrom. The mononuclear cells then are cultured in vitro. Patients with autoimmune disease develop characteristic white cell aggregates with autophagocytosis in the culture. Mononuclear cells from normal patients do not exhibit this cell aggregation with autophagocytosis. Excerpt(s): The present invention is directed to a method for diagnosing autoimmune diseases. The term "autoimmune diseases" is a generic term which describes a variety of illnesses in which a patient's body becomes the target of the patient's own immune system. As commonly used in the art, and as used herein, the term "autoimmune disease" includes such maladies as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, phagoneuroglanulomatosis, Hashimoto's disease, myasthenia gravis, cirrhosis, and many other autoimmune conditions. All of these disease states share the common characteristic that the immune system of the patient mounts an immunogenic assault upon the patient's own body. While there is presently no cure for most autoimmune diseases, there are treatment protocols which can ameliorate some of the suffering caused by many autoimmune diseases. The efficacy of these treatments is predicated largely upon accurate and early diagnosis of the autoimmune disease state of the patient. Consequently, there is an acute need for a diagnostic method which enables rapid, early, and accurate diagnosis of autoimmune disease states. Web site: http://www.delphion.com/details?pn=US05846758__

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Method for preparing a sample in a scan capillary for immunofluorescent interrogation Inventor(s): Dubrow; Robert S. (San Carlos, CA), Manian; Bala S. (Los Altos Hills, CA) Assignee(s): Biometric Imaging, Inc. (Mountain View, CA) Patent Number: 5,932,428 Date filed: October 28, 1996 Abstract: An assay and sample mixture for the enumeration of fluorescently stained target components of a whole blood sample by an imaging instrument. The sample preparation method ensures that the amount of target components per unit of volume of the whole blood sample is preserved by elimination of certain non-quantitative preparation steps while producing an even hematocrit layer within a scan capillary. Typical target components include white blood cells that express certain surface antigens, such as CD-4 and CD-8 proteins. To inhibit aggregation of the red blood cells, a reagent is added to an aliquot of whole blood sample. The aliquot of whole blood is mixed and with a preselected amount of a fluorescent dye and ligand complex which tags the target components. The sample and fluorescent complex are allowed to incubate a sufficient amount of time to bind enough of the fluorescent complex to the target components to provide a fluorescent signal from the target components which

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will be distinguishable from the fluorescent signal from the unbound fluorescent complex in the sample. The resulting mixture allows the imaging instrument to detect peak intensities of fluorescence from the target components, thereby allowing the target components to be volumetrically enumerated with an improved level of accuracy and efficiency. Excerpt(s): The present invention relates generally to the field of chemical and microbiological assay techniques and more specifically to a new and improved method of preparing a blood sample for cell classification and enumeration. Since the beginning of immunological research, researchers have desired to be able to enumerate, identify and analyze specific particles in biological fluids. In particular, bodily fluids of mammalian patients are often analyzed to enumerate target cellular components. For example, blood may be analyzed to determine the absolute count of T-lymphocytes per unit of volume of whole blood that positively express the CD4 or CD8 surface antigens. A CD4/CD8 blood test is important to determine the progression of the human immunodeficiency virus (HIV) throughout different stages of development and particularly for the diagnosis of acute development of the viral infection to Acquired Immune Deficiency Syndrome (AIDS). The quantity of testing required for diagnosis of the AIDS virus alone is fueling the demand for simplified, efficient methods for cell enumeration. To accomplish this objective, researchers have developed methods to mark specific cells with fluorescent markers that combine with a cell according to a specific cell traits or characteristics. Early immunologists used fluorescent dyes to stain the nucleus of white blood cells. The fluorescence from the dye or stain made it easier to enumerate and identify white blood cells. The breakthrough of monoclonal antibody technology soon permitted the conjugation of a monoclonal antibody with a fluorescent dye. This expanded the immunologist's ability to enumerate and classify cells according to their surface antigens. Web site: http://www.delphion.com/details?pn=US05932428__ •

Method for preserving a hemoglobin blood substitute Inventor(s): Gawryl; Maria S. (Charlestown, MA), Houtchens; Robert A. (Milford, MA), Light; William R. (Natick, MA) Assignee(s): Biopure Corporation (Cambridge, MA) Patent Number: 6,271,351 Date filed: October 14, 1998 Abstract: The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The invention also involves a method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulent to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized

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hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavanges oxygen, to form a stable polymerized hemoglobin bloodsubstitute, which is then packaged and stored in an atmosphere substantially free of oxygen. Excerpt(s): There exists a need for a blood-substitute to treat or prevent hypoxia resulting from blood loss (e.g, from acute hemorrhage or during surgical operations), resulting from anemia (e.g., pernicious anemia or sickle cell anemia), or resulting from shock (e.g, volume deficiency shock, anaphylactic shock, septic shock or allergic shock). The use of blood and blood fractions as in these capacities as a blood-substitute is fraught with disadvantages. For example, the use of whole blood often is accompanied by the risk of transmission of hepatitis-producing viruses and AIDS-producing viruses which can complicate patient recovery or result in patient fatalities. Additionally, the use of whole blood requires blood-typing and cross-matching to avoid immunohematological problems and interdonor incompatibility. Human hemoglobin, as a blood-substitute, possesses osmotic activity and the ability to transport and transfer oxygen, but it has the disadvantage of rapid elimination from circulation by the renal route and through vascular walls, resulting in a very short, and therefore, a typically unsatisfactory half-life. Further, human hemoglobin is also frequently contaminated with toxic levels of endotoxins, bacteria and/or viruses. Non-human hemoglobin suffers from the same deficiencies as human hemoglobin. In addition, hemoglobin from nonhuman sources is also typically contaminated with proteins, such as antibodies, which could cause an immune system response in the recipient. Web site: http://www.delphion.com/details?pn=US06271351__ •

Method for quantitating leukocyte count in whole blood sample Inventor(s): Hatanaka; Yoshihiro (Shizuoka-ken, JP), Serizawa; Ryo (Shizuoka-ken, JP) Assignee(s): Asahi Kasei Kabushiki Kaisha (Osaka, JP) Patent Number: 6,599,713 Date filed: August 10, 2001 Abstract: Disclosed is a method for determining a white blood cell count of a whole blood sample, which comprises: mixing a whole blood sample with a surfactant to thereby obtain a mixture; allowing the mixture to stand for a time sufficient to lyze the white blood cells contained in the whole blood sample and release intrinsic myeloperoxidase from the white blood cells; measuring the concentration of the released myeloperoxidase in the mixture; and determining the white blood cell count in the whole blood sample, based on the concentration of the released myeloperoxidase. Also disclosed is a method of the present invention, in which, in addition to a white blood cell count of a whole blood sample, the concentration of C-reactive protein contained in the same whole blood sample is measured. Excerpt(s): The present invention relates to a method for determining a white blood cell count of a whole blood sample. More particularly, the present invention is concerned with a method for determining a white blood cell count of a whole blood sample, which comprises: mixing a whole blood sample with a surfactant to thereby obtain a mixture; allowing the mixture to stand for a time sufficient to lyze the white blood cells contained in the whole blood sample and release intrinsic myeloperoxidase from the white blood cells; measuring the concentration of the released myeloperoxidase in the mixture; and determining the white blood cell count in the whole blood sample, based

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on the, concentration of the released myeloperoxidase. By the method of the present invention for determining a white blood cell count, the determination of a white blood cell count and/or a neutrophil count of a whole blood sample can be performed easily and rapidly without the need to separate blood cells from the whole blood sample. Further, by the determination method of the present invention, in addition to a white blood cell count of a whole blood sample, the concentration of C-reactive protein contained in the same whole blood sample can be measured, so that the presence or absence of an infectious disease and the graveness of an inflammation can be diagnosed rapidly and easily and at low cost. In recent years, in the initial steps of diagnosis of patients, as examination items for judging whether or not patients have a bacterial infectious disease, the white blood cell count of a whole blood sample and the concentration of C-reactive protein (hereinafter, frequently referred to simply as "CRP") contained in a whole blood sample are determined. In this connection, for enabling doctors to take adequate measures, such as the administration of an antibiotic, it has been desired to develop determination techniques which can produce results rapidly and easily and at low cost. Usually, the determination of the white blood cell count is performed using a commercially available automated blood cell counting apparatus which is based on the aperture-impedance method, wherein the apparatus is represented by COULTER COUNTER.TM. (manufactured and sold by COULTER ELECTRONICS, INC., the U.S.A.). However, the concentration of CRP, which is a plasma protein, cannot be determined by such an apparatus. Web site: http://www.delphion.com/details?pn=US06599713__ •

Method for quantitatively measuring white blood cells esterase activity in urine Inventor(s): Carter; Jesse M. (Tampa, FL), Smith; Jack V. (St. Petersburg, FL) Assignee(s): Chimera Research & Chemical, Inc. (Largo, FL) Patent Number: 5,776,780 Date filed: April 12, 1996 Abstract: Detecting white blood cells in an aliquot of urine by placing the aliquot of urine in an automated analyzer sampling cup, transferring the urine to a cuvette and injecting at least one reagent composition. The reagent composition contains a buffer, an activator such as benzalkonium chloride, an indicator and at least one substance to remove substances in the urine that cause interference with colorimetric photometry. The aliquot of urine is read in accordance with a preprogrammed code at a monochromatically specified wavelength to compare absorbance of the patient's urine with a known standard containing a known concentration of white blood cells. Excerpt(s): This invention relates to a method and materials that are designed for use in automating urinalysis. This system is designed to analyze urine for its constituents by a method that is fully automated (does not require the use of manual methods such as refractometer, pH meter, dipsticks, or impregnated test strips). Automation as designed by this system is directed to the use of a self-operating instrument that is capable of handling multiple reagents designed for use on an automated analyzer system for the quantitative determination of white blood cells in urine. It is known that the most common method for the analysis of urine is by the use of a manual technique known as a dipstick. This method for the analysis of urine is labor, time intensive, and costly among other detriments. The use of a dipstick for analysis of urine also relies on the subjective interpretation of the technician. The dipstick method requires the technician to submerge the dipstick in a sample of urine and remove it, wait a specified time, then

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compare the color development of the test on the dipstick to a color chart. Even more cumbersome methods involve the use of a refractometer, pH meter, or manual chemistry test. The assay devices utilizing prior art includes dry tablets, dipsticks, or impregnated test strips for the analysis of urinary constituents. None of these prior devices foresees or teaches a multiple/single liquid reagent system designed specifically for auto-analyzers to analyze urinary constituents quantitatively. Web site: http://www.delphion.com/details?pn=US05776780__ •

Method for rapid diagnostic of urinary tract infections Inventor(s): Drocourt; Jean-Louis (Yerres, FR), Foissac; Louis (Neuilly Sur Seine, FR), Groner; Warren (Great Neck, NY) Assignee(s): Chemunex (Maisons-Alfort, FR) Patent Number: 5,858,697 Date filed: June 20, 1996 Abstract: Method for the rapid diagnostic of an infection of the urinary tract (UTI), by a specific examination of urine.The method of analyzing a urine specimen, for the rapid and simultaneous counting of both viable bacteria and leucocytes (white blood cells or WBC), consists of:(1) simultaneous labeling of said bacteria and said white blood cells (WBC) present in said urine specimen, with a fluorescent viability marker of bacteria, said marker tagging and accumulating in both bacteria and white blood cells, under the same conditions and leading to different fluorescent elements;(2) automatically counting all the fluorescent elements by photoelectric detection of the fluorescent marker; and(3) simultaneously classifying said fluorescent elements in fluorescent viable bacteria and in fluorescent white blood cells, in view to obtain in one part the total number of bacteria and on the other part, the total number of white blood cells, on the basis of their size. Excerpt(s): The instant invention relates to a method for the rapid diagnostic of an infection of the urinary tract (UTI), by a specific examination of urine. Two laboratory findings are more particularly carried out in case of an infection of the urinary tract, i.e. count of white blood cells (pyuria) and culture of microorganisms (bacteriuria). bacteriuria without pyuria indicates contamination of the specimen or colonization of the bacteria in the urine without tissue invasion. Web site: http://www.delphion.com/details?pn=US05858697__

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Method for simultaneous analysis of cell viability, nucleated red blood cells and white blood cell differentials Inventor(s): Kim; Young Ran (Sunnyvale, CA), Mehta; Suresh N. (Pleasanton, CA), Sagala; Josefino C. (San Jose, CA), Yee; Michael W. (Sunnyvale, CA) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,879,900 Date filed: May 5, 1997 Abstract: A method for the simultaneous and quantitative, flow cytometric analysis of nucleated red blood cells (NRBC), white blood cells (WBC), damaged white blood cells and a white blood cell subclass differential (WBC/Diff) is provided. The method includes mixing an aliquot of a whole blood sample with a reagent system comprising a

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red blood cell (RBC) lysing component which lyses RBCs and NRBCs while minimizing damage to WBC cellular membranes and a membrane-impermeant nucleic acid stain which stains exposed NRBC nuclei and damaged WBCs, subjecting the stained aliquot to flow cytometric light measurements, obtaining at least one signal for the parameters of fluorescence (FL) and scattered light at a first and a second range of scatter angles, qualifying the obtained signals using AND/OR logic wherein to be qualified, a signal must be greater than the second scatter signal threshold AND also greater than either the first scatter signal threshold OR the FL threshold, constructing a three-dimensional plot of qualified intensity signals of fluorescence and scattered light from the detected signals, and differentiating the NRBC, WBC, damaged WBC and WBC/Diff from the constructed three-dimensional plot and determining the number of cells of each. Excerpt(s): This invention relates to a method for the simultaneous and quantitative analysis of damaged white blood cells (WBC), nucleated red blood cells (NRBC) and white blood cell sub-populations (WBC/Diff). More particularly this invention relates to differentiating WBC, NRBC, damaged WBC a WBC subclass differential (WBC/Diff) in a whole blood sample by the use of multi-dimensional light scatter and fluorescence analysis and a lysing reagent capable of lysing red blood cells (RBC) without damaging WBC cellular membranes. A major problem in automating a NRBC method for use on a clinical flow cytometer has been that since NRBC are rare events and RBC populations are so numerous, NRBC populations are not easily detected among the red blood cell ("RBC") population by either the differences in the cell's electrical resistivity (impedance measurements) or its light scattering characteristics (optical measurements). Although many attempts have been made to count NRBC among WBC populations, instead of among RBC population, these efforts have not generally been successful. Automated clinical hematology instruments, such as the Technicon H*1.RTM., Coulter STK.RTM. S and Abbott Cell-Dyn.RTM. 3000 and 3500 instruments only "flag" samples for the possible presence of NRBC if the sample dot plot shows increased noise signals below the lymphocyte cluster. This type of flagging very often produces false positive results since the elevated noise level could be due to PLT clumps, giant PLT or incompletely lysed RBC. In addition, it is extremely difficult to obtain an accurate Total WBC count and WBC Differential ("WBC/Diff") on samples containing NRBC because of the interference. Additionally, blood smears of the flagged samples must be examined and counted under the microscope by a skilled technician to obtain accurate WBC differential and NRBC counts. This is a very labor-intensive and subjective process. Web site: http://www.delphion.com/details?pn=US05879900__ •

Method of inhibiting PADGEM-mediated or ELAM-1-mediated leukocyte adhesion using an inhibitor comprising a Le.sup.x core component Inventor(s): Furie; Barbara C. (Wellesley, MA), Furie; Bruce (Wellesley, MA), Larsen; Eric (Lebanon, NH), Palabrica; Theresa (Quincy, MA), Sajer; Susan A. (Brookline, MA), Wagner; Denisa D. (Wellesley, MA) Assignee(s): New England Medical Center Hospitals, Inc. (Boston, MA) Patent Number: 5,807,745 Date filed: January 26, 1995 Abstract: The present invention relates to a method of inhibiting (reducing or preventing) the interaction of a cell which bears a surface molecule that interacts with a ligand comprising a Le.sup.x core with its target ligand by contacting the cell with an inhibitor comprising a Lewis x (Le.sup.x) core. The invention further relates to a method

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of inhibiting (reducing or preventing) the interaction or adhesion of endothelial cells and/or platelets with leukocytes (i.e., white blood cells), especially with nonlymphocytic leukocytes such as neutrophils and monocytes, by contacting the endothelial cells and/or platelets with an inhibitor comprising a Le.sup.x core under conditions whereby adhesion is inhibited. Excerpt(s): The LECCAMs or selectins, including Mel-14 antigen, LAM-1 (LECAM1), ELAM-1 (LECAM2), and PADGEM (LECAM3), are a newly recognized class of cellular adhesion molecules that are characterized structurally by the presence of a lectin-like domain, an epidermal growth factor-like domain, a variable number of cysteine-rich repeats related to those found in a family of complement regulatory proteins, a transmembrane domain, and a short cytoplasmic tail (Osborn, L., Cell 62: 306 (1990)). These cell adhesion molecules are thought to function in the adhesion of leukocytes to endothelial cells. For example, the Mel-14 antigen and its human analog, LAM-1, which are present on the surface of lymphocytes, are thought to be involved in the targeting of lymphocytes to endothelial cells within high endothelial venules (Siegelman, M. H. et al., Science, 243: 1165-1172 (1989); Tedder, T. F. et al., J. Exp. Med., 170: 123-133,(1989)). The endothelial leukocyte adhesion molecule-1, or ELAM-1, is synthesized and expressed on endothelial cells after stimulation with specific cytokines, and mediates the interaction of endothelial cells with neutrophils, monocytes and cell lines with monocyte-like features ((Bevilacqua, M. P. et al., Proc. Natl. Acad. Sci. USA, 84: 92389242 (1987); Bevilacqua, M. P. et al., Science, 243: 1160-1165 (1989); Hession, C. L. et al., Proc. Natl. Acad. Sci. USA, 87: 1673-1677, 1990). The platelet activation dependent granule-external membrane protein, PADGEM, has been cloned and has a typical LECCAM structure, with a lectin domain, an epidermal growth factor domain, nine complement binding repeat domains, a transmembrane domain, and a cytoplasmic domain (Johnston, G. I. et al., Cell, 56: 1033-1044, (1989)). PADGEM, which is also referred to as GMP-140, CD62, or LECAM3, is found on the endothelial cell surface as well as on the surface of platelets. In endothelial cells, PADGEM is stored as a component of the Weibel-Palade bodies (Bonfanti, R. et al., Blood 73: 1109-1112, (1989)), and in platelets, it is stored as a component of the alpha granule membrane. Following granule exocytosis, PADGEM is expressed on the cell surface (Hsu-Lin, S. C. et al., J. Biol. Chem., 259: 9121-9126, (1984); Berman, C. L. et al., J. Clin. Invest., 78: 130-137 (1986); McEver, R. P. and Martin, M. N., J. Biol. Chem., 259: 9799-9804, (1984); Stenberg, P. E. et al., J. Cell Biol., 101: 880-886 (1985); Hattori, R. et al., J. Biol. Chem., 264: 7768-7761 (1989)). PADGEM is also found in megakaryocytes, which are the precursors of platelets. (Beckstead et al., Blood 67: 285-293 (1986)). Web site: http://www.delphion.com/details?pn=US05807745__ •

Method of screening for genetic predisposition to anticholinesterase therapy Inventor(s): Soreq; Hermona (Rishon le Zion, IL), Zakut; Haim (Savyon, IL) Assignee(s): Yissum Research Development Company of Hebrew University of Jerusalem (Jerusalem, IL) Patent Number: 5,807,671 Date filed: January 9, 1995 Abstract: A method of screening for a genetic predisposition to anticholinesterase exposure. The method includes the steps of obtaining a peripheral blood sample, and then analysing serum from the blood sample for BuChE levels and inhibitorsusceptibilites. The DNA of peripheral white blood cells from the blood sample is also

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screened for the presence of BuChE alleles thereby identifying patients who have a genetic predisposition to anticholinesterase exposure. Excerpt(s): The present invention relates to a method for screening for a genetic predisposition for adverse responses to anticholinesterase therapy. The clinical uses of anticholinesterases (anti-ChEs) have recently been extended in two major developments, involving many new subjects. First, during the 1991 Gulf War, the carbamate, pyridostigmine was administered prophylactically to over 400,000 soldiers, with the intention of transiently blocking (and thus protecting) a fraction of their nervous system acetylcholinesterase (AChE, EC 3.1.1.7), in anticipation of nerve agent attacks (Gavageran, 1994; Ember, 1994). Yet more recently, the reversible cholinesterase (ChE) inhibitor, tetrahydroamino acridine (THA, tacrine, Cognex.RTM.) was approved for use in patients with Alzheimer's disease, for the purpose of enhancing the availability of acetylcholine at synapses and improving residual cholinergic neurotransmission in patients suffering from massive degeneration of cholinergic neurons (Knapp et al., 1994). Adverse symptoms were reported in both groups (Ember, 1994; Gavageran, 1994; Winker, 1994), including responses characteristic of cholinergic deficits, such as depression, general fatigue, insomnia and weight loss. However, these were only a few out of many symptoms in a complex and diverse list, the interpretation of which was complicated by incomplete medical records and the stressful situation experienced by the first group and the generally bad condition of the aging patients from the second group. Web site: http://www.delphion.com/details?pn=US05807671__ •

Method of separating leukocytes from blood cells using a leukodepletion filter Inventor(s): Johnson; Richard J. (Mundelein, IL), Ung-Chhun; Neng S. (Lincolnshire, IL) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 5,795,483 Date filed: March 4, 1997 Abstract: Novel blood cell fractionation means utilizes conventional filters coated with high molecular weight polyethylene oxide derivatives crosslinked to prevent leaching from filter surfaces. These fractionation means have a special efficacy in binding white blood cells from whole blood while simultaneously allowing red cells and platelets to pass in the effluent phase. Excerpt(s): In processing whole blood for therapeutic administration to patients, it is desirable to separate the various cellular components. In particular, it is desirable to remove leukocytes because of their role in mediating immunologic reactions which can cause adverse clinical events such as allosensitization. For a review of adverse clinical sequellae to transfusion, see Sekiguchi, et al., Leucocyte-depleted blood products and their clinical usefulness, Ch. 5, pg. 26-33, from The Role of Leucocyte Depletion in Blood Transfusion Practice (1988). Furthermore, leukocytes are unessential for therapeutic supplementation of cell deficiencies in patients involving platelets and red cells. Thus, filter systems have been devised for passaging blood cells in order to remove leukocytes while allowing platelets or red blood to pass through for subsequent recovery. There have been a number of approaches reported for leukocyte depletion. U.S. Pat. No. 4,330,410 discloses a packed fiber mass with leukodepletion properties comprising fibers of cellulose acetate, acrylonitrile, polyamide, or polyester. U.S. Pat. No. 4,925,572 discloses use of a gelatin coating to inhibit red blood cell (RBC) and platelet adhesion.

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Leukodepletion is accomplished primarily through physical entrainment of the cells in the fiber body, and adhesion of RBCs and platelets results from the gelatin coating. U.S. Pat. No. 4,936,998 discloses a strategy for leukodepletion in which a hydrophilic monomer containing hydroxyl or amido groups and functional nitrogen-containing groups such as primary or secondary amino groups is coated onto a filter matrix of known fibers such as polyester, polyamide, etc. Modification of fiber surfaces has also been used to obtain materials with improved cell separation properties. For example, U.S. Pat. No. 4,130,642 discloses a packed column in which the packing material comprises an Egyptian cotton which has been de-fatted and bleached so that RBC readily pass through the column. Web site: http://www.delphion.com/details?pn=US05795483__ •

Protein-colloidal metal-aminodextran coated particle and methods of preparation and use Inventor(s): Burshteyn; Alexander (Hialeah, FL), Gordon; Kristie (Coral Gables, FL), Maples; John A. (Miami Shores, FL), Rodriguez; Carlos M. (Miami, FL), Siiman; Olavi (Davie, FL), Whitesell; James Keller (Austin, TX) Assignee(s): Coulter International Corp. (Miami, FL) Patent Number: 5,945,293 Date filed: October 9, 1997 Abstract: A stable colloidal particle comprises a colloidal-sized core substrate having amine-reactive functional groups thereon with an aminodextran coating over its peripheral surface and a layer of colloidal-sized metallic solid overlaying the aminodextran coating. A linker comprising aminotrithiolate attached to the metallic solid has a free amino group to which a protein is attached by covalent bonding to the free amino group. Such novel particles are useful in flow cytometry, particularly useful in the simultaneous analyses of subpopulations of leukocytes. Methods of preparation of such particles, as well as methods of use are provided. These conjugates enable the simultaneous analyses of at least two different mutually exclusive subsets of white blood cells, based on the binding affinity of the conjugated protein. Excerpt(s): This invention generally relates to novel flow cytometry, and cell separation, reagents, and more particularly to novel particles, in which a protein is conjugated to a colloidal-metal coated, aminodextran coated substrate and methods of preparation and use thereof. The technique of flow cytometry provides investigators with data on physical parameters of cells which can be used to separate various classes of cells, e.g., to classify white blood cells (leukocytes) into three major groups, namely, lymphocytes, monocytes and granulocytes. Other techniques have been described to identify additional leukocyte populations, for example, T-cells, B-cells, cytotoxic cells and suppressor cells, neutrophil, eosinophil, and basophils. See, e.g., Flow Cytometry and Sorting, page 371; edited by Melamed, Mullaney, and Mendelsohn, 1979, John Wiley & Sons, N.Y., N.Y.; U.S. Pat. No. 5,125,737; U.S. Pat. No. 5,492,833; U.S. Pat. No. 5,223,398; U.S. Pat. No. 5,231,005. The enumeration of subclasses using antibody-coated polystyrene latex beads to target specific white blood cell subpopulations in whole blood, hence, producing a change (a shift) in the targeted cell volume, direct or low frequency current (DC) or high frequency (RF) conductivity, and light scatter (S) has been described. See, e.g., PCT Publication WO92/09682 published Jun. 11, 1992; J. C. Hudson et al, Cytometry, 22:150 (1995), U.S. Pat. No. 5,639,620 and International Patent application No. WO95/24631, published Sep. 14, 1995. In fact, these latter changes can

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be detected on the commercially available hematology instruments, such as the COULTER.RTM. STKS instrument equipped with VCS technology. Such instruments can calculate the percentage of shifted cell population in the total population of white blood cells. Web site: http://www.delphion.com/details?pn=US05945293__ •

Pulsed administration of compositions for the treatment of blood disorders Inventor(s): Perrine; Susan P. (27 Harding Ave., Braintree, MA 02184) Assignee(s): none reported Patent Number: 5,939,456 Date filed: July 26, 1996 Abstract: The invention relates to novel compositions and to methods for the pulsed administration of compositions to a patient or to cells in vitro for the treatment of human blood disorders. Compositions contain chemical compounds that stimulate the expression of fetal hemoglobin and/or stimulate the proliferation of red blood cells, white blood cells and platelets in patients and ex vivo for reconstitution of hematopoiesis in vivo. These methods are useful to treat or prevent the symptoms associated with anemia, sickle cell disease, thalassemia and other blood disorders. The invention also relates to methods for the pulsed administration of compositions to patients for the treatment and prevention of cell proliferative disorders including deficiencies such as cytopenia and malignancies such as viral-induced tumors, other forms of neoplasia and for expansion of cells for hematopoietic transplantation. Pulsed administration has been shown to be more effective than continuous therapy in patients tested. Excerpt(s): The invention relates to methods for the treatment and prevention of blood disorders such as anemia, neutropenia, thrombocytopenia, thalassemia and sickle cell disease. These methods comprise the administration of compositions that stimulate the expression of a globin protein and, in particular, fetal hemoglobin, or the proliferation or development of hemoglobin expressing, myeloid cells or megakaryocytic cells. The major function of red blood cells is to transport oxygen to tissues of the body. Minor functions include the transportation of nutrients, intercellular messages and cytokines, and the absorption of cellular metabolites. Anemia, or a loss of red blood cells or red blood cell capacity, can be grossly defined as a reduction in the ability of blood to transport oxygen. Anemia can be measured by determining a patient's red blood cell mass or hematocrit. Hematocrit values are indirect, but fairly accurate measures of the total hemoglobin concentration of a blood sample. Anemia, as measured by a reduced hematocrit, may be chronic or acute. Chronic anemia may be caused by extrinsic red blood cell abnormalities, intrinsic abnormalities or impaired production of red blood cells. Extrinsic or extra-corpuscular abnormalities include antibody-mediated disorders such as transfusion reactions and erythroblastosis, mechanical trauma to red cells such as micro-angiopathic hemolytic anemias, thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. In addition, infections by parasites such as Plasmodium, chemical injuries from, for example, lead poisoning, and sequestration in the mononuclear system such as by hypersplenism can result in red blood cell disorders and deficiencies. Impaired red blood cell production can occur by disturbing the proliferation and differentiation of the stem cells or committed cells. Some of the more common diseases of red cell production include aplastic anemia, hypoplastic anemia, pure red cell aplasia and anemia associated with renal failure or endocrine disorders.

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Disturbances of the proliferation and differentiation of erythroblasts include defects in DNA synthesis such as impaired utilization of vitamin B.sub.12 or folic acid and the megaloblastic anemias, defects in heme or globin synthesis, and anemias of unknown origins such as sideroblastic anemia, anemia associated with chronic infections such as malaria, trypanosomiasis, HIV, hepatitis virus or other viruses, and myelophthisic anemias caused by marrow deficiencies. Web site: http://www.delphion.com/details?pn=US05939456__ •

Quality control material and calibrator for nucleated red blood cell tested on hematology analyzer Inventor(s): Hagbloom; Robin (Claremont, CA), Wang; Fu-sheng (Thousand Oaks, CA) Assignee(s): Sysmex Corporation (Kobe, JP) Patent Number: 6,448,085 Date filed: April 13, 2001 Abstract: A method for the quality control of nucleated red blood cells on a hematology analyzer using a mixture of human and animal blood, particularly chicken blood and fixed human blood with nucleated red blood cells. The control material illustrated good stability over a fifty day period when stored at 4 degrees Celsius. The cell morphology showed good cell shape and the equipment had a stable nucleated red blood cell number and nucleated red blood cell per 100 white blood cells number. The method is used for quality control as for calibration for nucleated red blood cell counting or staging, on a hematology analyzer. Excerpt(s): The present invention generally relates to methods for counting and staging of nucleated red blood cells (NRBC). More specifically, the present invention relates to the quality control and calibration of nucleated red blood cell counting and staging on automatic hematology analyzers, which allows the hematology analyzers to use the methods to ensure a mode of accurate and precise counting and staging. The invention is directed to using a new control material for nucleated red blood cell counting and staging. In a clinical laboratory, particularly when a cell analyzer is used, a calibrator and quality control material is necessary to enable the instrument to perform at a continuously optimal level to ensure accurate and precise results that can be reported. For example, when using a hematology analyzer, fresh blood is used as a control material. Fixed blood and various types of latex beads are used to provide longer control times to observe any change in a given time frame and observe data results for any necessary calibration change. Web site: http://www.delphion.com/details?pn=US06448085__

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Simultaneous analyses of white blood cell subsets using multi-color, multi-intensity fluorescent markers in flow cytometry Inventor(s): Burshteyn; Alexander (Hialeah, FL), Mylvaganam; Ravindra (Hollywood, FL), Siiman; Olavi (Davie, FL), Wilkinson; Julie (Weston, FL) Assignee(s): Coulter International Corp. (Miami, FL) Patent Number: 5,994,089 Date filed: November 21, 1997

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Abstract: A method for a single-measurement quantification of multiple populations of white blood cells (WBC) is based upon the labeling of different pairs of cell populations, each pair containing mutually exclusive cell receptors which are expressed at substantially similar receptor densities with labeled ligands for each receptor. One cell population is labeled with a ligand capable of binding to a first cell surface receptor which ligand is directly conjugated to a fluorescent phycobiliprotein or tandem dye; and a second cell population is labeled with a ligand capable of binding to a second cell surface receptor, which ligand is cross-linked by an aminodextran to a fluorescent phycobiliprotein or tandem dye. The phycobiliproteins upon laser excitation produce a different detectable fluorescence intensity for each cell population. Use of such pairs of conjugates enable two populations of cells with similar receptor densities to be distinguished with the use of a single color marker. Further use of additional ligands to other cell surface receptors and additional phycobiliprotein or tandem dye, or other markers in the same manner, enables the simultaneous quantification of up to 45 different cell populations with one laser line and four fluorescent colors. Excerpt(s): The present invention relates to methods for analyses of cell populations using fluorescent labels or markers. More specifically, the method employs a combination of such markers directly bound to a ligand for an appropriate cell surface receptor and such markers conjugated via an aminodextran to a ligand for a second cell surface receptor. Differences in fluorescent signals emitted by the different types of ligand-conjugated markers expand the number of cell subsets that can be detected at any one time. Multiplex labeling of cells for analysis of mixed cell populations by flow cytometry has progressed in various ways. Only a finite number of fluorescence emission colors of known organic fluorophores can be squeezed into the visible-nearUV-near-IR spectral regions in which flow cytometry measurements are made. The limitations have been dictated by the bandwidths of emission bands, the spectral overlap between these emission bands, and the excitation wavelength requirements. Up to eight colors requiring three laser lines have been introduced in various stages: two- to four-color [H. M. Shapiro in PRACTICAL FLOW CYTOMETRY, 3rd ed., Wiley-Liss, Inc., New York, N.Y., 1995, Chap. 7, p. 291]; five color [A. J. Beavis and K. J. Pennline, Cytometry, 15: 371-376 (1994); M. C. O'Brien et al, Cytometry, 21:76-83 (1995); M. Roederer et al, Cytometry, 21: 187-196 (1995)]; six color [M. Roederer et al, Cytometry, 24: 191-197 (1996)]; seven color for imaging [T. Ried et al, Proc. Natl. Acad. Sci. USA, 89: 1388-1392 (1992); A. Gothot et al, Cytometry, 24: 214-225 (1996)]; and eight color [M. Roederer et al, Tissue Antigens, 48: 485 (1996), abstract TC-6-02]. The six and seven color cases appear to represent the present upper limit for flow cytometry applications in which known organic dyes are used as fluorescent labels, since the eight-color example cannot as yet be considered to be of clinical significance due to severe overlap between emission bands of the fluorochromes. As the upper limit in the number of usable colors was reached, other methods, based on fluorescence intensity differences, either intrinsic to analyzed cell populations or contrived by various means, have been described. Mutually exclusive pairs of targeted white blood cell populations with widely different, intrinsic numbers of receptors per cell can be labeled by a single color marker and analyzed by flow cytometry [U.S. Pat. No. 5,538,855, issued Jul. 23, 1996]. U.S. Pat. No. 4,499,052, issued Feb. 12, 1985 describes a method of distinguishing multiple subpopulations of cells by labeling specific antibodies with fluorescent polymers containing different, pre-selected ratios of fluorescein and rhodamine [see also, A. M. Saunders and C.-H. Chang, Ann. N. Y. Acad. Sci., 468:128 (1986)]. H. M. Shapiro in PRACTICAL FLOW CYTOMETRY, 1st ed., Alan R. Liss, Inc., pp. 127-128 (1985) describes a method using three different antibodies labeled with fluorochrome A, B, and a combination of A and B. U.S. Pat. No. 5,206,143, issued Apr. 27, 1993 describes

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saturated and sub-saturated amounts of marker mixed with the sample of cells. Quantitative differences in fluorescence intensity of one or two fluorochromes used for labeling cells were obtained. Each subset to be analyzed was labeled with a different amount of fluorochrome, exhibiting fluorescence intensities within a distinguishable range. Mixtures of fluorescein- and phycoerythrin-labeled and unlabeled antibodies were used to produce fluorescence intensity differences of several orders of magnitude among various cell subsets [P. K. Horan et al, Proc. Natl. Acad. Sci. USA, 83: 8361-8365 (1986)]. Use of this method to identify helper and suppressor/cytotoxic T cells, NK and B cells, and monocytes in whole blood was shown [C.-M. Liu et al, Am. J. Clin. Path, 92: 721-728 (1989)]. Further, eight leukocyte subsets in whole blood were analyzed with six monoclonal antibodies linked with one of three fluorochromes [P. Carayon et al, J. Immunol. Methods, 138: 257-264 (1991)]. Web site: http://www.delphion.com/details?pn=US05994089__ •

Single channel, single dilution detection method for the identification and quantification of blood cells and platelets in a whole blood sample using an automated hematology analyzer Inventor(s): Jones; Valentine (Malahide, IE), Zelmanovic; David (Monsey, NY) Assignee(s): Bayer Corporation (Tarrytown, NY) Patent Number: 6,524,858 Date filed: March 31, 2000 Abstract: The invention provides a new single channel, single dilution method and system for identifying, analyzing and quantifying the cellular components of whole blood using a single channel, rather than multiple channels, of an automated hematology analyzer utilizing flow cytometry and the detection of the light scattered and absorbed by each cell. The single channel utilized in the method was previously known and used only for red blood cell and reticulocyte analysis. The method involves the use of an organic dye in the reagent solution for staining the nucleic acid of reticulocytes, including reticulated platelets, and white blood cells in the sample. The single channel method developed and described is particularly useful for determining white blood cell counts and assessing parameters of a whole blood sample, for blood samples from both human and non-human mammals. The single channel method of the invention employs only one blood diluent reagent composition that is mixed with the blood sample aliquot for analysis and, optimally, a sheath/rinse reagent, thus making it simpler and easier to use. In addition, the reagent compositions of the method are more benign to the white blood cells than previous reagents, which contained various lytic surfactants for removing red blood cells, for example. The apparatus for performing the method provides an economical, streamlined and space-saving analyzer for carrying out complete blood cell analysis on a mammalian whole blood sample. Excerpt(s): The present invention relates generally to an economical single channel method and system for detecting, identifying and quantifying different blood cell types, including platelets, in a mammalian blood sample, including human and non-human whole blood cell samples. Hemoglobin analysis is also provided by the method and system of the present invention. The method and system of the invention are particularly economical and useful for automated hematology analyzers utilizing flow cytometry systems. The detection, identification and quantification of cellular and particulate blood components in a whole blood sample are necessary and customary parameters of blood sample analysis using hematology analyzers involving flow

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cytometry. A number of semi-automated and automated hematology analyzers can perform blood sample analyses; however, advancements in the technology of hematology analyzers and systems to afford further refinement, economy and accuracy to blood sample analysis advance and improve the ability to distinguish the various blood cell types and perform the necessary blood component analyses on whole blood samples. Examples of automated hematology analyzers suitable for distinguishing and quantifying red blood cells, including mature red blood cells (RBCs) and reticulocytes, white blood cells (WBCs), including neutrophils, lymphocytes, monocytes, eosinophils and basophils; platelets; and hemoglobin include, but are not limited to the Bayer (formerly Technicon) H*.TM. Systems series of hematology analyzers (including H*3.TM. and H*Next.TM. Systems) and the ADVIA.RTM. 120 Hematology System, which are developed and sold by the assignee hereof. The Bayer ADVIA.RTM. 120 System is a quantitative multi-channel, multi-dilution automated hematology analyzer that provides red blood cell and platelet analyses, as well as leukocyte (i.e., white blood cell) and reticulocyte analysis for in vitro diagnostic use in clinical laboratories. Web site: http://www.delphion.com/details?pn=US06524858__ •

Steroid sulfatase assay Inventor(s): Purohit; Atul (South Harrow, GB3), Reed; Michael J. (London, GB3) Assignee(s): Imperial College of Science, Technology and Medicine (London, GB2) Patent Number: 5,891,620 Date filed: June 2, 1997 Abstract: An assay comprising determining the absence or presence of steroid sulphatase activity is described. In a preferred embodiment, the assay uses white blood cells. The assay can be used to determine if an agent is an in vitro and/or in vivo steroid sulphatase inhibitor. Excerpt(s): The present invention relates to an assay. In particular the present invention relates to an assay for use in determining the absence or presence of steroid sulphatase activity. Steroid precursors, or pro-hormones, having a sulphate group in the 3-position of the steroid nucleus, referred to hereinafter simply as steroid sulphates, are known to play an important part as intermediates in steroid metabolism in the human body. Oestrone sulphate and dehydroepiandrosterone (DHA) sulphate, for example, are known to play an important role as intermediates in the production, in the body, of oestrogens such as oestrone, oestradiol and oestrogenic steroids such as androstenediol. Web site: http://www.delphion.com/details?pn=US05891620__

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Synthetic polymer particles for use as standards and calibrators in flow cytometry Inventor(s): DeClercq; Ronny (Aalter, BE), Kuckert; Eberhard (Leverkusen, DE), Louwet; Frank (Diepenbeek, BE), Moskalski; William (Elmsford, NY), Podszun; Wolfgang (Cologne, DE), Zelmanovic; David (Monsey, NY) Assignee(s): Bayer Corporation (Tarrytown, NY) Patent Number: 6,074,879 Date filed: June 17, 1998

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Abstract: The invention describes novel methods for calibrating or standardizing flow cytometry instruments using synthetic polymer particles or beads having physical properties which provide advantages for their use in such instruments. The polymer particles or beads employed in the calibration methods are spherical, have an average particle diameter of from about 1 to about 8 microns, a relatively narrow particle distribution, and a low refractive index, i.e., from about 1.35 to about 1.45. The particles are safe, stable for long time periods and are particularly suitable for employment as hematology analyzer calibration substances. The invention provides an advantageous improvement over the types of standards currently used to calibrate a variety of instruments that rely on light scatter combined with other parameters to identify and measure biological particles or cells, as well as nonbiological particles. In particular, using the calibration/standardization method and polymer particles according to the present invention allows hematology instruments to be calibrated and standardized for subsequent accurate and reliable determinations of red blood cells, reticulocytes, white blood cells and platelets in whole blood samples. Excerpt(s): The present invention relates to products and methods used in flow cytometry instrumentation for the analysis of biological particles or cells. More particularly, the invention relates to synthetic polymer materials and methods for standardizing or calibrating flow cytometry instruments prior to using the instruments for analyzing such particles, for example, the cellular components of whole blood. The analysis of particles, particularly biological particles, and cells is routinely performed using a variety of commercially-available instruments which determine the characteristics of such particles based on one or more light-related signals which pass through the instrument. Flow cytometers allow the determination of the characteristics of particles using techniques in which the particles are moving in a liquid stream or carried in a suspension. Typically, in flow cytometry instruments, cells or other biological particles flow in a liquid stream so that each particle, virtually one cell at a time, passes through a sensing region that is capable of measuring the physical or chemical characteristics of the particles. A variety of signals associated with different characteristics of the particles under analysis may be detected. Such signals include electrical, acoustical, optical and radioactive. Flow cytometers generally rely on optical signals for the analysis of particles which pass through the instrument. Whether or not an instrument analyzes particles in a static or a dynamic state, those skilled in the art will appreciate that calibration and standardization are required prior to performing particle analyses. Under normal circumstances, calibration occurs as one or more preliminary presteps in preparing instruments for proper use and measurement and to ensure accurate and reliable assay results. This is especially important since cells, or other biological particles, are extremely small and the signals to be detected, in relation to the size of the cells or particles, are often at a low magnitude. Web site: http://www.delphion.com/details?pn=US06074879__ •

Treatment for inflammatory bowel disease with VLA-4 blockers Inventor(s): Burkly; Linda C. (West Newton, MA), Lobb; Roy R. (Westwood, MA) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 5,932,214 Date filed: October 15, 1997 Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule

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recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut. Excerpt(s): The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4) in the treatment of IBD. Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups. Severe side effects are associated with the drugs commonly prescribed for IBD, including nausea, dizziness, changes in blood chemistry (including anemia and leukopenia), skin rashes and drug dependence; and the surgical treatments are radical procedures that often profoundly alter the everyday life of the patient. Accordingly, there is a great need for treatments for IBD that are effective yet less severe in their side effects and are less invasive of the IBD sufferer's body and quality of life. Web site: http://www.delphion.com/details?pn=US05932214__ •

Use of arabinogalactan in a sperm wash product Inventor(s): Ellington; Joanna E. (Valleyford, WA), Oliver; Sylvia Adams (Spokane, WA) Assignee(s): Advanced Reproduction Technologies Inc. (Spokane, WA) Patent Number: 5,879,877 Date filed: February 9, 1996 Abstract: A sperm solution including arabinogalactan is provided which is useful for separating the motile sperm, to produce sperm samples which are suitable for use in a variety of diagnostic and research applications. In one embodiment, the solution includes an effective amount of arabinogalactan to permit washing or separation of the sperm, while maintaining sperm viability during the washing or separation procedure. Using the improved sperm wash, non-sperm substances that are capable of having a detrimental effect on sperm viability, such as seminal plasma, white blood cells, red blood cells, freezing extender agents, sperm debris, and media components, can be removed from the sperm sample. The inclusion of arabinogalactan in the solution has a protective effect on sperm in a sperm sample during processing. In a preferred embodiment, the arabinogalactan is ultrarefined. The improved sperm solution is compatible with sperm samples obtained from variety of different mammals, including human, bovine and equine sperm samples. The washed sperm can be used in a variety of diagnostic or research protocols including infertility testing, sperm toxicology testing and in vitro fertilization. Excerpt(s): The present invention is generally in the area of improved solutions containing arabinogalactan for washing and separating sperm. Sperm must be washed prior to use in most diagnostic or research protocols, such as infertility testing, in vitro fertilization and freezing. Washing is done to limit damage to the sperm cell by components of seminal plasma, such as antibodies, white blood cells, red blood cells

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and bacteria. Washing also removes dying or dead sperm which release enzymes and other products which are toxic to healthy sperm. Generally, sperm are separated by allowing the motile sperm to swim away from the debris (sperm swim-up), by centrifuging the sperm through a gradient and collecting a pellet of live sperm (washing), or by passing the sperm through a column that binds the dead or unhealthy sperm. Each of these current techniques has its own disadvantages. Swim-up only recovers a small number of the normal sperm. Column methods have poor selectivity for the normal sperm in the ejaculate. Centrifugation through a density gradient results in high sperm recovery but also can produce products which are toxic to sperm, so that an additional wash step is required to remove the products. Centrifugation also can produce sperm with reduced motility and fertility during in vitro fertilization. Parrish et al., Theriogenology, 44:859-869 (1995); and Tanphaichitr et al., Gamete Research, 20:6781 (1988). Web site: http://www.delphion.com/details?pn=US05879877__ •

White blood cell hematology control Inventor(s): Ryan; Wayne L. (Omaha, NE) Assignee(s): Streck Laboratories, Inc. (Omaha, NE) Patent Number: 5,981,282 Date filed: January 21, 1997 Abstract: Reference controls comprised of aldehyde-fixed white blood cells stabilized red blood cells and simulated blood platelets exhibiting a white blood cell histogram profile that is substantially that of whole blood are obtained by the addition of a lipoprotein to the control and an antioxidant to inhibit lysis of stabilized red blood cells by said lipoprotein. Excerpt(s): The present invention relates to a method for preparing a hematology reference control and calibrator for hematology instruments used to measure granulocytes, lymphocytes, monocytes, eosinophiles and basophiles. There are several hematology instruments which can analyze blood to determine the number of granulocytes, monocytes, lymphocytes, eosinophiles and basophiles. These instruments include the Coulter STKS, UNIPATH 3000, TOA NE 8000, TECHNICON H-1 and TECHNICON H-6000. Because these instruments employ different methods to measure the five populations of white cells, it has been necessary to employ a different type of reference control with each instrument. This fact has necessitated that the user stock separate controls for each of the types of instruments. From the user's standpoint, this situation is not only inconvenient, but can be expensive as well. It is an object of the present invention to provide a reference control that can be used in a variety of hematology instruments. Web site: http://www.delphion.com/details?pn=US05981282__

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Patent Applications on White Blood Cells As of December 2000, U.S. patent applications are open to public viewing.7 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 white blood cells: •

Adjuvant immune therapy in the treatment of solid tumors through modulation of signaling pathways following engagement of humoral and cell mediated responses Inventor(s): Guilford, F. Timothy; (Palo Alto, CA), Kindness, George; (Middletown, OH), Schumm, Brooke III; (Ellicott City, MD) Correspondence: Brooke Schumm, Iii; Daneker, Mcintire, Schumm, Prince, Goldstein, ET A; 210 N Charles ST; Suite 800; Baltimore; MD; 21201; US Patent Application Number: 20020187130 Date filed: June 13, 2001 Abstract: The invention combines a novel combination with two especially important aspects: first, the invention proposes to simultaneously stimulate response in white blood cells and a patient's tumor cells with a mitogen-challenging compound, preferably a lectin, in the preferred mode the selected lectin being phytohemagglutin ("PHA"), and second, to generate heat shock protein. A method of treatment is set out. The method of manufacturing proposed utilizes a system calculated to better insure sterility and streamline production of the cytokine modulator. A method of testing in conjunction with the therapy is also claimed utilizing clinical assessment of disease activity, patient performance status, and quality of life questionnaire. Should efficacy of a treatment fall off, particularly because of mutation or adaption, the composition and method may be re- applied. The invention is not limited to humans, but is also applicable to mammals. The composition is usable as a stand-alone composition, but preferably is used in conjunction with standard therapy such as radiation, chemotherapy or surgery, particularly surgical therapy, and in conjunction with the administration of cystine, as later defined, to enhance immune system competency. Excerpt(s): This is a continuation in part pursuant to 37 C.F.R. 1.78 of Prov. Appl. No. 60/263,486 filed on Jan. 23, 2001 and of a provisional application bearing the above name being filed simultaneously to this specification in June, 2001. The inventors propose a composition with immunogenic properties acting like an anti-cancer vaccine, method of treatment, and method of administration. The composition is referred to as a cytokine modulator. The composition is usable as a stand-alone composition, but preferably is used in conjunction with standard therapy such as radiation, chemotherapy or surgery, particularly surgical therapy, and in conjunction with the administration of cystine, as later defined, to enhance immune system competency. The invention combines a novel combination with two especially important aspects: first, the invention proposes to simultaneously stimulate response in white blood cells and a patient's tumor cells with a mitogen-challenging compound, preferably a lectin, in the preferred mode the selected lectin being phytohemagglutin ("PHA"), and second, to generate heat shock protein. A method of treatment is set out. The method of manufacturing proposed utilizes a system calculated to better insure sterility and streamline production of the cytokine modulator. A method of testing in conjunction with the therapy is also claimed utilizing clinical assessment of disease activity, patient

7

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

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performance status, and quality of life questionnaire. Should efficacy of a treatment fall off, particularly because of mutation or adaption, the composition and method may be re-applied. The invention is not limited to humans, but is also applicable to mammals. All references to humans can be applied to mammals generally and the use of you, the body or human references are not intended to be limiting. Current oncological research provides no clearly adequate answer for solid tumors refractory to standard therapy. Multiple therapeutic measures have been studied, but the effectiveness of any single approach to date has been limited by the heterogeneous nature of cancer and the characteristics of tumor growth. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antimicrobial blood treatment using allicin and related compounds Inventor(s): Goodrich, Laura L.; (Lakewood, CO) Correspondence: Greenlee Winner And Sullivan P C; 5370 Manhattan Circle; Suite 201; Boulder; CO; 80303; US Patent Application Number: 20030077264 Date filed: September 18, 2002 Abstract: Methods and compositions prolonging the storage life and/or increasing the safety of a blood product, such as whole blood, red blood cells, white blood cells, platelets, serum and aqueous additive solutions for storage of such blood products are provided. Storage solutions of this invention comprise a composition selected from the group consisting of garlic extract, allicin, other microorganism-growth-inhibiting compounds derived from garlic, and analogs and derivatives of allicin and said other compounds, in an amount effective to inhibit growth of at least one selected microorganism which is a bacterium, virus, fungus or parasite. The storage additive solutions of this invention can increase platelet storage life by at least about 20%, preferably at least about 40%. Excerpt(s): This application claims priority to U.S. provisional application No. 60/323,669 filed Sep. 20, 2001, which is incorporated herein by reference in its entirety to the extent not inconsistent herewith. Fermented with rice bran and Aspergillus, then extracted with ethanol, garlic is said to be useful as a coating agent for treating diseases of trichophytosis. (PCT Publication 88/04933 dated Jul. 14, 1988 for "Specially Processed Garlic Product" (Abstract)). Enzymatically-deactivated and fermented with Aspergillus and/or Monascus, it is known as a prophylactic or therapeutic agent for diabetes, hepatic disease, cancer, immunopathy, and hyperemia. (U.S. Pat. No. 6,146,638 issued Nov. 14, 2000 to Kakimoto et al. for "Fermented Garlic Composition.") Extracts have been recommended for inhibiting apoptosis. (U.S. Pat. No. 5,635,187 issued Jun. 3, 1997 to Bathurst et al. for "Compositions which Inhibit Apoptosis, Methods of Purifying the Compositions and Uses Thereof.") A composition made by combining extract of garlic with S-allylcysteine is said to be useful in controlling hepatopathy and oncogenesis. (U.S. Pat. No. 5,093,122 issued Mar. 3, 1992 to Kodera for "Method for Preparing an SAllylcysteine-containing Composition." Garlic and extracts have been orally administered for treating and preventing cardiovascular diseases such as myocardial infarction, stroke and multiple arteriosclerosis by reduction of high levels of plasma homocysteine. (U.S. Pat. No. 6,129,918 issued Oct. 10, 2000 to Amagase for "Method and Pharmaceutical Composition for Reducing Serum Homocysteine Concentration.") U.S. Pat. No. 5,705,152 issued Jan. 6, 1998 to Plummer for "Antimicrobial Composition" discloses the use of dried garlic powder in combination with non-pathogenic

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microorganisms useful for combating pathogenic microorganisms in animal gastrointestinal tracts. Other components of garlic and their degradation products are described in L. D. Lawson et al. (1991), "Identification and HPLC Quantitation of the Sulfides and Dialk(en)yl Thiosulfinates in Commercial Garlic Products," Planta Med. 57:363-370. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apoptotic entities for use in treatment of neurodegenerative and other neurological disorders Inventor(s): Bolton, Anthony E.; (Tideswell, GB), Mandel, Arkady; (North York, CA), Sauder, Daniel; (Toronto, CA) Correspondence: Gerald F. Swiss, ESQ.; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020044924 Date filed: May 25, 2001 Abstract: Treatment and/or prophylaxis, in mammalian patients, of neurodegenerative and other neurological medical disorders is effected by administering to the patient effective amounts of apoptotic bodies and/or apoptotic cells, preferably those derived from the patient's own white blood cells, e.g. by extracorporeal treatment of the patient's blood cells to induce apoptosis and administration of the apoptotic bodies and/or cells so formed to the patient. Excerpt(s): This invention relates to biochemical and biological compositions and to the uses thereof in the treatment and/or prophylaxis of various neurodegenerative and other neurological disorders in mammalian patients. More particularly, it relates to treatment and prophylaxis of neurodegenerative and other neurological disorders by administration of compositions containing the mammalian cellular materials and fragments thereof, and to the compositions containing the mammalian cellular materials and fragments themselves, and to processes for preparing such compositions. Two mechanisms of cell death in the body are recognized, necrosis and apoptosis. Apoptosis is the process of programmed cell death, described by Kerr et al in 1992 [Kerr J F R, Wyllie A H, Currie A R (1992). "Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. "British Journal of Cancer 26: 239-257"], by which steady-state levels of the various organ systems and tissues in the body are maintained as continuous cell division and differentiation takes place. Cells undergoing apoptosis often exhibit distinctive morphological changes such as a pronounced decrease in cell volume, modification of the cytoskeletons resulting in pronounced membrane blebbing, a condensation of the chromatin, and degradation of the DNA into oligonucleosomal fragments. Following these morphological changes, an apoptotic cell may break up into a number of small fragments known as apoptotic bodies, consisting essentially of membrane-bound bodies containing intact organelles, chromatin etc. Apoptotic bodies are normally rapidly removed from the body by phagocytosis by macrophages, dendritic cells and other antigen presenting cells, before they can become lysed and release their potentially pro-inflammatory intracellular contents. Degradation phase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Blood processing method and apparatus Inventor(s): Pages, Etienne; (Segny, FR) Correspondence: Cesari And Mckenna, Llp; 88 Black Falcon Avenue; Boston; MA; 02210; US Patent Application Number: 20020032112 Date filed: June 12, 2001 Abstract: The invention is directed to blood processing method and apparatus utilizing a centrifugation bowl with a filter core disposed within the bowl. The centrifugation bowl includes a rotating bowl body defining an enclosed separation chamber. A generally cylindrical filter core is disposed inside the separation chamber. The filter core includes a filter membrane that is sized to block at least white blood cells, but to allow plasma to pass through. The filter core is generally arranged within the separation chamber such that plasma is forced to pass through the filter core before being removed from the centrifugation bowl. The addition of the filter core provides an efficient, lowcost method for recovering a "purer" plasma fraction from a donor. Excerpt(s): The invention relates to centrifugation bowls for separating blood and other similar fluids. More specifically, the present invention relates to a centrifugation bowl having a rotating filter core for use in recovering a plasma fraction from whole blood. Human blood predominantly includes three types of specialized cells (i.e., red blood cells, white blood cells, and platelets) that are suspended in a complex aqueous solution of proteins and other chemicals called plasma. Although in the past blood transfusions have used whole blood, the current trend is to collect and transfuse only those blood components or fractions required by a particular patient. This approach preserves the available blood supply and in many cases is better for the patient, since the patient is not exposed to unnecessary blood components, especially white blood cells, which can transmit pathogens. Two of the more common blood fractions used in transfusions are red blood cells and plasma. Plasma transfusions, in particular, are often used to replenish depleted coagulation factors. Indeed, in the United States alone, approximately 2 million plasma units are transfused each year. Collected plasma is also pooled for fractionation into its constituent components, including proteins, such as Factor VIII, albumin, immune serum globulin, etc. Individual blood components, including plasma, can be obtained from units of previously collected whole blood through "bag" centrifugation. With this method, a unit of anti-coagulated whole blood contained in a plastic bag is placed into a lab centrifuge and spun at very high speed, subjecting the blood to many times the force of gravity. This causes the various blood components to separate into layers according to their densities. In particular, the more dense components, such as red blood cells, separate from the less dense components, such as white blood cells and plasma. Each of the blood components may then be expressed from the bag and individually collected. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions and administration of compositions for the treatment of blood disorders Inventor(s): Perrine, Susan P.; (Weston, MA) Correspondence: Nixon Peabody Llp; Attention: David Resnick; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20010027215 Date filed: April 30, 2001 Abstract: The invention relates to novel compositions and to methods for the pulsed administration of compositions to a patient or to cells in vitro for the treatment of human blood disorders. Compositions contain chemical compounds that stimulate the expression of fetal hemoglobin and/or stimulate the proliferation of red blood cells, white blood cells and platelets in patients and ex vivo for reconstitution of hematopoiesis in vivo. These methods are useful to treat or prevent the symptoms associated with anemia, sickle cell disease, thalassemia, blood loss, and other blood disorders. The invention also relates to methods for the pulsed administration of compositions to patients for the treatment and prevention of cell proliferative disorders including deficiencies such as cytopenia and malignancies and for expansion of cells for hematopoietic transplantation. Pulsed administration has been shown to be more effective than continuous therapy in patients tested. Excerpt(s): The invention relates to composition methods for the treatment and prevention of blood disorders such as anemia, neutropenia, thrombocytopenia, thalassemia and sickle cell disease using such compositions. The compositions include C.sub.1-C.sub.4 substituted and/or phenyl substituted carboylic acids such as dimethyl substitutions onto carboxylic acids. The methods comprise the administration of compositions that stimulate the expression of a globin protein and, in particular, fetal hemoglobin, or the proliferation or development of hemoglobin expressing, myeloid cells or megakaryocytic cells. The major function of red blood cells is to transport oxygen to tissues of the body. Minor functions include the transportation of nutrients, intercellular messages and cytoldnes, and the absorption of cellular metabolites. Anemia, or a loss of red blood cells or red blood cell capacity, can be grossly defined as a reduction in the ability of blood to transport oxygen. Anemia can be measured by determining a patient's red blood cell mass or hematocrit. Hematocrit values are indirect, but fairly accurate measures of the total hemoglobin concentration of a blood sample. Anemia, as measured by a reduced hematocrit, may be chronic or acute. Chronic anemia may be caused by extrinsic red blood cell abnormalities, intrinsic abnormalities or impaired production of red blood cells. Extrinsic or extra-corpuscular abnormalities include antibody-mediated disorders such as transfusion reactions and erythroblastosis, mechanical trauma to red cells such as micro-angiopathic hemolytic anemias, thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. In addition, infections by parasites such as Plasmodium, chemical injuries from, for example, lead poisoning, and sequestration in the mononuclear system such as by hypersplenism can result in red blood cell disorders and deficiencies. Impaired red blood cell production can occur by disturbing the proliferation and differentiation of the stem cells or committed cells. Some of the more common diseases of red cell production include aplastic anemia, hypoplastic anemia, pure red cell aplasia and anemia associated with renal failure or endocrine disorders. Disturbances of the proliferation and differentiation of erythroblasts include defects in DNA synthesis such as impaired utilization of vitamin B.sub.12 or folic acid and the megaloblastic anemias, defects in heme or globin synthesis, and anemias of unknown origins such as sideroblastic anemia,

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anemia associated with chronic infections such as malaria, trypanosomiasis, HIV, hepatitis virus or other viruses, and myelophthisic anemias caused by marrow deficiencies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

G-CSF conjugates Inventor(s): Andersen, Kim Vilbour; (Broenshoej, DK), Hansen, Christian Karsten; (Vedbaek, DK), Mikkelsen, Jan Moller; (Gentofte, DK), Nissen, Torben Lauesgaard; (Palo Alto, CA), Schambye, Hans Thalsgaard; (Frederiksberg, DK) Correspondence: Maxygen, INC.; 515 Galveston Drive; Red Wood City; CA; 94063; US Patent Application Number: 20030118612 Date filed: July 10, 2002 Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF. Excerpt(s): This application is a continuation-in-part of co-pending U.S. application Ser. No. 09/904,196 filed Jul. 11, 2001. Pursuant to 35 U.S.C.sctn.119(a)-(d), this application also claims priority from and benefit of Danish Patent Application No. PA 2002 00447 filed Mar. 22, 2002, and Danish Patent Application No. PA 2002 00708 filed May 8, 2002. U.S. Ser. No. 09/904,196 is a continuation-in-part of U.S. application Ser. No. 09/760,008 filed Jan. 10, 2001. U.S. Ser. No. 09/760,008 claims priority to and benefit of U.S. Provisional Application Serial No. 60/176,376 filed Jan. 14, 2000, U.S. Provisional Application Serial No. 60/189,506 filed Mar. 15, 2000, U.S. Provisional Application Serial No. 60/215,644 filed Jun. 30, 2000, Danish Patent Application No. PA 2000 00024 filed Jan. 10, 2000, Danish Patent Application No. PA 2000 00341 filed Mar. 2, 2000, and Danish Patent Application No. PA 2000 00943 filed Jun. 16, 2000. The disclosure of each application listed above is incorporated herein in its entirety for all purposes. Pursuant to 37 C.F.R.sctn.1.71(e), Applicants note that a portion of this disclosure contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. The present invention relates to new polypeptides exhibiting granulocyte colony-stimulating factor (G-CSF) activity, to conjugates between a polypeptide exhibiting G-CSF activity and a non-polypeptide moiety, to methods for preparing such polypeptides or conjugates and the use of such polypeptides or conjugates in therapy, in particular for the treatment of neutropenia or leukopenia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hematology composition using preserved white blood cells in combination with source particles to simulate native white blood cells and method of making same Inventor(s): Carver, Frank J.; (Marco Island, FL), Lapicola, James D.; (Pleasant Hill, CA) Correspondence: B. Trent Webb; Shook, Hardy & Bacon L.L.P.; 1200 Main Street; Kansas City; MO; 64105-2118; US Patent Application Number: 20020022269 Date filed: June 8, 2001 Abstract: A hematology control composition and method of making the composition is provided. The control employs a plurality of components including a synthetic plasma component, a red blood cell component, a platelet component and a leukocyte component. The leukocyte component includes at least one subpopulation having particles derived from other than white blood cells. Excerpt(s): Not Applicable. This invention generally relates to the field of hematology. More particularly, this invention relates to a hematology control composition made from a unique combination of elements which simulates vertebrate white blood cells. Further, the present invention relates to a method of making such a hematology control composition. Instrumentation useful in analyzing blood components and chemistry has been used for many years. Over time, the accuracy and sensitivity of such hematology instruments have steadily advanced. Early hematology instrumentation has evolved into relatively complex machinery which analyzes the discrete components of blood based upon the intricate and subtle characteristics of its components. The most recently developed automated hematology instrumentation is capable not only of detecting red blood cells and platelets, but also is capable of conducting a multi-part analysis of human white blood cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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High concentration white cells, a method for agglomeration of the high concentration and a bag set for use in conjunction therewith Inventor(s): Coelho, Philip Henry; (El Dorado Hills, CA), Rubinstein, Pablo; (New Rochelle, NY), Stevens, Cladd E.; (New York, NY) Correspondence: Craig J. Arnold; Amster, Rothstein & Ebenstein; 90 Park Avenue; New York; NY; 10016; US Patent Application Number: 20010034513 Date filed: May 15, 2001 Abstract: A therapeutic product formed from a high concentration of white blood cells having a high degree of cell viability. The white blood cells are sequestered from their normal population presence in whole blood by placing the blood into a container and preventing coagulation of the blood, separating the blood into two components, one of which is extremely rich in white blood cells through the use of a reagent and centrifugation, sequestering the white cell concentration, and freezing the white cells. Excerpt(s): The following invention is directed generally to the therapeutic utilization of white blood cells, a technique for sequestering the white blood cells by causing them to coalesce in a population density greater than they normally occur in nature, and a method for causing an enriched concentration in conjunction with an array of bags oriented in a set that facilitates both the concentration process and a method for

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preserving the white blood cells. It is now recognized that placenta/umbilical cord blood (PB) contains large numbers of hematopoietic stem and progenitor cells that endow PB with extraordinary therapeutic capabilities in the reconstitution of bone marrow damaged as a result of inherited diseases, accidents or medical procedures. As in the case of ordinary collection of bone marrow for transplantation, PB contains immune cells potentially capable of mounting specific responses against the recipients of such transplants, but in contrast to adult immunological cells, those in PB display a lower, perhaps much lower tendency to produce damaging immune responses against the recipient. The clinical syndrome produced by the immuno responses of the graft against the recipient's cells and tissues is designated "Graft versus Host Disease" (GVHD). In the typical clinical situation, the recipient's own immune response against the graft is abrogated by drugs and irradiation treatments designed to reduce or eliminate the immunological and other hematopoietic cells and thus avoid the host versus graft immune reaction that would cause rejection of the graft. It has been proven that the principal targets of these Graft versus Host and Host versus Graft immune reactions are antigens encoded by the genes of the HLA (Human Leukocyte Antigen) system and that successful outcomes of bone marrow transplants are dependent on the sharing of HLA antigens by donor and recipient. Sibling donors who have inherited the same paternal and maternal HLA genes present in the recipient are HLA-identical and thus, optimal from this viewpoint. Patients lacking such HLA-identical sibling donors must receive transplants from more distant relatives or from unrelated donors. Because the HLA system includes several discrete genes each of which displays an extremely large number of antigenically different variants in the population, such distant relativedonor or unrelated-donor transplants must be expected to contain a variable number of HLA incompatibilities unless they are selected from among potential donors by identifying the specific variants present in each and choosing donors whose HLA antigens match those of the recipient. To perform this selection with significant probability of success, it is necessary to have access to large panels of potential donors whose HLA antigens are known. In the case of unrelated donor PB, this requires establishing a bank of frozen HLA-typed units collected from random placentas. Heretofore, the most widely accepted method for freezing PB consisted of adding to the whole PB unit an equal volume of a cryopreservative solution, with the double disadvantage that the volume of each cryopreserved unit becomes very large and that a relatively large amount of possibly deleterious cryopreservative is eventually administered to the recipients of such PB units. Administration of cryoprotectant and hemoglobin from erythrocytes destroyed by using a freezing and thawing method designed to protect the stem and progenitor cells but not the erythrocytes may have toxic effects generally and especially on specific organs such as the kidney of the recipient. In addition, there is the logistical consequence that a large number of freezers would be needed to contain useful numbers of the large volume frozen units in reserve, with the attending increase in up-front and running costs. The applicants have developed a practical method that allows a substantial reduction of the volume of PB Units by eliminating the unneeded mature red blood cells and an equivalent volume of plasma. This submission describes this method and a specially designed set of plastic bags and connecting tubes intended to facilitate the accomplishment of the desired concentration of the needed stem cells and progenitor cells with minimal manipulation and risk of contamination. Essentially, this method will allow an experimental, time consuming laboratory process to become a routine procedure in blood banks. The following submission reflects the state of the art of which applicant is aware insofar as these documents appear germane to the patent process. However, it is respectfully stipulated that none of these patents teach singly nor render obvious when considered

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in any conceivable combination the nexus of the instant invention as set forth hereinafter. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

In vivo treatment of joint disease using interleukin-1 Inventor(s): Frisbie, David D.; (Fort Collins, CO), McIlwraith, C. Wayne; (Fort Collins, CO) Correspondence: Janelle D. Waack; Howrey Simon Arnold & White Llp; 750 Bering Drive; Houston; TX; 77057-2198; US Patent Application Number: 20030091536 Date filed: March 7, 2002 Abstract: Adenovirus particles encoding an interleukin-1 receptor antagonist were found to be effective in treating joint disease over an extended period of time when administered directly via arthrocentesis.Administration of the adenovirus particles resulted in an increase in interleukin-1 receptor antagonist protein concentration, increased influx of white blood cells, increased percentage of neutrophils, and a lower percentage of mononuclear cells when compared to control experiments. Excerpt(s): The invention relates to the in vivo treatment of joint disease using gene therapy. In particular, in vivo administration of vectors encoding interleukin-1 receptor antagonists is disclosed. Joint disease is a severe mobility and career modifying disease in man and horses (Robert Davis, Horses give a leg up to human knee research, U.S.A. Today, Apr. 6, 1999, at 10D). The etiopathogenesis of joint disease is not clearly understood, however, may mediators that lead to degeneration within the joint environment have been identified. Cytokines, especially interleukin-1 and tumor necrosis factor, have been defined as initiating mediators of a degenerative cascade that propagates joint disease. Through the use of anti-cytokine proteins it has been demonstrated that blocking these molecules can significantly alter the course of joint disease. These studies have mainly been performed on experimentally created joint disease. Furthermore, both the effects on naturally occurring disease and long-term outcomes of joint disease have yet to be adequately studied using anti-cytokine therapies. Over the last decade, gene transfer has become an accepted and even preferred method of continuous protein expression targeting certain disease conditions although the optimal vector for use in gene transfer is still undetermined. Early in the genesis of gene transfer protocols the use of retroviral vectors predominated for various practical and safety reasons. Some of these reasons include the ability to harvest cells, transduce them in vitro, and after safety testing, introduce the altered cells into the recipient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for measuring white blood cell count Inventor(s): Law, Wai Tak; (Moorestown, NJ), Nikolyukin, Inna; (Moorestown, NJ), Nikolyukin, Yuri; (Moorestown, NJ) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030215951 Date filed: May 20, 2002 Abstract: A method for quantitatively measuring white blood cell count involves capture of white blood cells from a fluid sample by a retainer, removal of the red blood cells and other interfering substances by a wash solution, and reading the result of a color reaction in which an ester which is present on the white blood cells cleaves a chromogenic substrate which produces a water insoluble dye. The apparatus for use in the present method includes a retainer for white blood cells that optionally has a dye substrate immobilized therein and an absorption layer that wicks and takes up all excess washing solution flowing past the sample. Excerpt(s): The present invention relates to a method and device for establishing a white blood cell count in biological fluids in the presence of interfering substances. A white blood cell (WBC) count is one of the most commonly tested parameters in clinical laboratories. A laboratory WBC usually requires 5-10 ml. of venous blood, and the patient may have to wait up to three days for the laboratory results. Generally, methods for estimating WBC in biological fluids are based on automated cell counting technologies, in which the sample is diluted, and cells of different sizes and shapes are counted in a flow cell (U.S. Pat. Nos. 2,656,508; 3,502,973; 6,159,740). Instruments based on flow technology are expensive and require professionally trained personnel for running in a clinical laboratory environment. New analyzers using nanotechnology for flow cells are much smaller than the traditional cell counting instruments, but they are still in the development stage. Also, the complicated mechanical pump and valves systems required limit the options for manufacturers to offer a low cost instrument. There are many instances in which rapid measurements of white blood cell count is important. Rapid measurements of the white blood cell count may be useful in a physician's office, where clinicians use these measurements to assess the effects of therapeutic drugs, cytostatic medications, and certain infections. Patients who are on chemotherapy also need to check their white blood cell count frequently to ensure that they are eligible for the next treatment, which may be a problem if they live at a distance from their physician or a hospital. Schizophrenic patients taking Clozapine must monitor their white blood cell counts weekly. Patients suffering from chronic infections may have white blood cell counts in excess of 10,000 cells per microliter, and should be monitored. Being able to monitor members of a large population after a radiological accident or terrorist attack would facilitate triage and planning for the best use of medical resources. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for assaying whole blood for the presence or absence of circulating cancer or other target cell fragments Inventor(s): Fiedler, Paul; (New Haven, CT), Levine, Robert A.; (Guilford, CT), Rimm, David L.; (Branford, CT), Wardlaw, Stephen C.; (Lyme, CT) Correspondence: William W. Jones; Patent Counsel; 6 Juniper Lane; Madison; CT; 06443; US Patent Application Number: 20010024802 Date filed: March 5, 2001 Abstract: This method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of fragments of target analyte cancer cells which are circulating in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis of the presence or absence of fragments of cancer cells relies on the detection of external or internal binding sites which are known to be present only in or on tumorous cancer cells. Fluorophors with distinct wavelength emissions are coupled with antibodies, or other binding moieties such as complementary nucleotide sequences, which antibodies are directed against the epithelial cell fragment membrane binding sites, such as internal or external surface epitopes on the cell fragments, or internal binding sites on cell organelles; and which nucleotide sequences are complementary to portions of cell fragment RNA and/or DNA. The labled binding agents are humoric or soluble in the blood sample. The labeled fluorometric binding site-specific materials may be coupled to small plastic beads which have a density or specific gravity that is preferably greater than the specific gravity or density of the red blood cells. The target cell fragments are less dense than the red cells, and typically have the same density or specific gravity as the platelets or white blood cells in the blood sample. Any of the labeled beads which couple with target cell analyte fragments will have a density or specific gravity that is less than the red cells in the blood sample. Thus cell fragment/labeled bead couples will gravitate into an area in the centrifuged blood sample which area is somewhere above the centrifuged red cell layer. The detection of the labeled target analyte/particle couples can be performed in situ in the centrifuged blood sample either visually or photometrically. Excerpt(s): This is a continuation-in-part of co-pending U.S. Ser. No. 08/976,886, filed Nov. 24, 1997, the contents of which are incorporated herein in their entirety. This invention relates to a method and assembly for assaying an anticoagulated whole blood sample for the presence or absence of circulating fragments of cancer cells or fragments of other target cells. The blood sample is contained in a transparent sampling container assembly and the assay can be performed in situ in the sampling tube assembly. More particularly, the method of this invention involves the centrifugal density-based separation of the contents of the blood sample in a manner which will ensure that any circulating target cell fragments in the blood sample are physically displaced by their density into a predetermined axial location in the blood sample and in the sampling container assembly, and also into a restricted optical plane in the sampling container assembly which is adjacent to the wall of the sampling container, and finally into a very well-defined zone of that optical plane. Cytology is the science and technology involved in the morphological characterization of mammalian cells. Cytology has clinical utility in both human and veterinary medicine. Cytology is most often used to diagnose the presence or absence of malignancy in exfoliated or harvested cells: a) that are shed into a body cavity such as the pleural space or peritoneum; b) that are shed into a body fluid that is excreted as, for example, sputum or urine; c) that are obtained by scraping or brushing a body surface, such as the uterine cervix, the uterine cavity, or bronchial

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mucosa; or d) that are obtained by direct needle-mediated aspiration from a tumor such as tumors of the thyroid, breast, lung, or the like. The exfoliated or harvested cells are then typically fixed, stained and visually studied, usually by bright field microscopy, and then, if needed, by immunologic stains and/or other molecular techniques. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for dispersing red and white blood cells Inventor(s): Meyer, Robert J.; (Penfield, NY), Tarnawskyi, Christine J.; (Webster, NY) Correspondence: Patent Documentation Center; Xerox Corporation; Xerox Square 20th Floor; 100 Clinton AVE. S.; Rochester; NY; 14644; US Patent Application Number: 20030012078 Date filed: August 15, 2002 Abstract: A method and apparatus for dispersal of aggregates of red and white blood cells and platelets. The present invention employs a sonic or ultrasonic device to efficiently breakup aggregates of red and white blood cells and platelets by driving the ultrasonic signal over a small range of frequencies around the acoustic slow wave frequency of the agglomerate. At this frequency, the fluid vibrates out of phase with the solid and is forced out through the pore structure in the agglomerate. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/699,804, filed Oct. 30, 2000. This invention is generally directed to a method and apparatus for dispersal of aggregates of red and white blood cells and platelets. The present invention employs a sonic or ultrasonic device to efficiently breakup aggregates of red and white blood cells and platelets by driving the ultrasonic signal over a small range of frequencies around the acoustic slow wave frequency of the agglomerate. At this frequency, the fluid vibrates out of phase with the solid and is forced out through the pore structure in the agglomerate. Compressional ultrasonic waves interact with particle aggregates, whether they are aggregates of blood cells or aggregates of pigment particles, in a limited number of ways. Each way can have its own set of technological advantages and disadvantages that make it suitable for some applications, and unsuitable for others. For example, the pressure within an ultrasonic wave is at a maximum at one location within the wave, called the peak, and at a minimum 1/2 wavelength away, at the valley. There is a stress exerted on a particle aggregate due to this difference in pressure. If that stress exceeds the yield stress of the aggregate, particle breakup occurs. However, for a compressional wave velocity of 1520 m/sec (velocity of sound in water) and a frequency of 10,000 kHz the wavelength is 15.2 cm. This approach is not appropriate for breaking up blood cell aggregates. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for preparing a platelet composition Inventor(s): Slichter, Sherrill J.; (Vashon, WA) Correspondence: Cesari And Mckenna, Llp; 88 Black Falcon Avenue; Boston; MA; 02210; US Patent Application Number: 20010053547 Date filed: July 6, 2001

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Abstract: Non-immunogenic and/or toleragenic platelet compositions, the compositions being substantially free of white blood cells and/or having the residual white blood cells inactivated are provided. Methods for preparing such compositions using various combinations of filtration, centrifugation and UV irradiation are also provided. Excerpt(s): This application is a Divisional of Serial No. 09/255,463, filed Feb. 22, 1999, now ______which is a Continuation-In-Part of Ser. No. 08/566,847, filed Dec. 4, 1995, now abandoned. The present invention relates generally to blood products, and more specifically to non-immunogenic and toleragenic platelet compositions, and methods of producing the same. Patients with a variety of disorders receive intermittent or chronic transfusion support or require tissue grafting to replace a defective organ. For individuals requiring transfusion support, they have either a genetic or acquired deficiency of one or more blood components that require replacement therapy. Many different products prepared from blood are available for transfusion, including both cellular and plasma components. However, repeated exposure to blood products often results in recipient recognition of the foreign transfused antigens. For instance, alloimmune platelet refractoriness occurs in up to 30%-60% of patients requiring repeated platelet transfusions. Such immune recognition of the foreign antigens results in a failure to achieve a benefit from the transfusion and in some circumstances may even cause a transfusion reaction with adverse consequences to the recipient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of nucleic acid recovery Inventor(s): Garvin, Alex M.; (Durmenach, FR) Correspondence: Rankin, Hill, Porter & Clark, Llp; 700 Huntington Building; 925 Euclid Avenue, Suite 700; Cleveland; OH; 44115-1405; US Patent Application Number: 20030170669 Date filed: December 24, 2002 Abstract: For reducing side effects of blood transfusion, white (nucleated) blood cells are separated from donated human blood by filtering the blood through filter media selectively adsorbing white blood cells. Such filter media are processed for recovering nucleic acids contained in the white blood cells. The cells retained by the filter media are separated from the filter media e.g. by washing with an aqueous solution. The separated cells are then lysed and the nucleic acids are isolated from the components of the lysed cells. Preferably each portion of filter medium is used for filtering the blood of one individual donor and is processed separately whereby samples of nucleic acids of one individual each are obtained. Excerpt(s): The invention concerns a method according to the generic part of the first independent claim. The inventive method serves for recovering nucleic acids from waste material, in particular for recovering human nucleic acids. Nucleic acids, i.e. DNAs and/or RNAs are the base material for genetic studies. If such studies are to regard human populations, large numbers of nucleic acid samples each representing one human individual are needed. Collecting nucleic acid samples representing a general human population depends on the agreement of each one of a representative plurality of individuals of this population and is therefore very difficult. Similar sampling is carried out on a large scale only in rare cases of crime in which cases relatively small samples of saliva are collected. The object of the invention is to provide a method for recovering nucleic acids, in particular human nucleic acids, from waste material which method is to

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be capable to furnish large amounts of nucleic acids for genetic studies or for any other section of science or industry requiring nucleic acids, in particular human nucleic acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method to determine an engrafting cell dose of hematopoietic stem cell transplant units Inventor(s): Fischer, Johannes; (Neuss, DE), Kogler, Gesine; (Dusseldorf, DE), Wernet, Peter; (Dusseldorf, DE) Correspondence: Jacobson Holman; 400 Seventh Street, N.W.; Washington; DC; 20004; US Patent Application Number: 20020094550 Date filed: November 2, 2001 Abstract: A method to determine an engrafting cell dose of hematopoietic stem cell transplant units from transplant sources having nucleated cells selected from the group consisting of cord blood, bone marrow, peripheral blood comprising the steps ofsubjecting the source to a substantially complete erythrocyte lysis,measuring in a cell counter a signal corresponding selectively to white blood cells,assessing essentially quantitatively nucleated red blood cell (NRBC) count as part of the total nucleated cell (NC) count,and determining the number of white blood cells (WBCs) as transplant relevant cells. Excerpt(s): This is a complete application claiming benefit of provisional No. 60/245,167 filed Nov. 3, 2000. The invention pertains a method to determine cell dose of hematopoietic stem cell transplant units from transplant sources having nucleated cells. Transplantation of hematopoietic stem and progenitor cells from umbilical-cord blood (CB) can restore the function of bone marrow and sustain hematopoietic recovery in both related and unrelated recipients (Gluckman, et al. 1989; Kutzberg, et al. 1996). For patients for whom no suitable related donor is available, this source of hematopoietic stem cells offers substantial advantages, because of the relative ease of procurement; the absence of risk to the donor; the small likelihood of transmitting clinically important infectious diseases such as cytomegalovirus (CMV) and Epstein-Barr (EBV) virus infections; the rapid availability of placental blood to transplantation centres; and the low risk of severe graft-versus-host disease (GVHD) when compared to unrelated bone marrow transplantation (Gluckman, et al. 1997; Rubinstein, et al. 1998). The reduced risk and severity of GVHD permits the use of transplants from HLA-mismatched CBs and improves the likelihood of finding transplant units for patients with uncommon tissue types. For these reasons, worldwide cord-blood banks have increased the use of cordblood transplantation in patients with hematologic disorders (Silberstein, et al. 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and apparatus for generating and utilizing linear moving optical gradients Inventor(s): Zhang, Haichuan; (San Diego, CA) Correspondence: Lyon & Lyon Llp; 633 West Fifth Street; Suite 4700; Los Angeles; CA; 90071; US Patent Application Number: 20020160470 Date filed: January 17, 2002

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Abstract: Apparatus and methods are provided for interacting light with particles, including but not limited to biological matter such as cells, in unique and highly useful ways. Optophoresis consists of subjecting particles to various optical forces, especially optical gradient forces, and more particularly moving optical gradient forces, so as to obtain useful results. In one implementation, a population of particles, comprising two or more differing particles, e.g., red blood cells and white blood cells, are illuminated by a line of light which is moved slowly relative to the particle population. The particles are moved with the line until the population is aligned. Next, the line of particles is subject to relative motion of light relative to the particles, such as by rapidly moving the line of illumination relative to the physical position of the particles. By moving the line away from the particles at a rate great enough that certain particles remain behind, effective separation, characterization and/or identification of the particles may be made. Optionally, the direction of the low initial scan is in a direction opposition to the more rapid scan after the particles have been aligned. Excerpt(s): This invention relates to methods and apparatus for the selection, identification, characterization, and/or sorting of materials utilizing at least optical or photonic forces. More particularly, the inventions find utility in biological systems, generally considered to be the use of optical forces for interaction with bioparticles having an optical dielectric constant. This application is a continuation-in-part of application Ser. No. 09/993,377, filed Nov. 14, 2001, entitled "Methods and Apparatus for Generating and Utilizing a Moving Optical Gradient", which is a continuation-inpart of application Ser. No. 09/845,245, filed Apr. 27, 2001, entitled "Methods and Apparatus for Use of Optical Forces for Identification, Characterization and/or Sorting of Particles", which is related to application Ser. No. 09/843,902, filed on Apr. 27, 2001, entitled "System and Method for Separating Micro-Particles", with named inventor Osman Kibar, which claims priority from provisional application Ser. No. 60/248,451, entitled "Method and Apparatus for Sorting Cells or Particles", filed Nov. 13, 2000. Those applications are incorporated herein by reference as if fully set forth herein. Separation and characterization of particles has a wide variety of applications ranging from industrial applications, to biological applications, to environmental applications. For example, in the field of biology, the separation of cells has numerous applications in medicine and biotechnology. Historically, sorting technologies focused on gross physical characteristics, such as particle size or density, or to utilize some affinity interaction, such as receptor-ligand interactions or reactions with immunologic targets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and apparatus for separation of particles Inventor(s): Delbert Antwiler, Glen; (Lakewood, CO), Taylor, Linda A.; (Littleton, CO) Correspondence: Gambro, Inc; Patent Department; 10810 W Collins Ave; Lakewood; CO; 80215; US Patent Application Number: 20030116512 Date filed: December 4, 2002 Abstract: The present invention is directed to a method and system that separates first particles from second particles, or white blood cells from red blood cells, by sedimentation in a fluid chamber with debulking of one of the first or second particles or red blood cells through the inlet of the fluid chamber. The method and system further includes fractionation of the remaining particles or white blood cells into selected subsets. In one embodiment of the instant invention a blood product containing white

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blood cells is loaded in a separation chamber, a diluting or sedimenting agent is added to encourage rouleaux formation of any red blood cells, the cells are sedimented and the red blood cells are removed. Excerpt(s): This Application claims priority to U.S. provisional application Serial No. 60/338,938, filed Dec. 5, 2001, which is incorporated herein by reference in its entirety to the extent not inconsistent herewith. The present invention relates to a system and method for separating particles. The invention has particular advantages in connection with separating white blood cells into desired subsets and debulking red blood cells from such white blood cells. This application is related to U.S. Pat. No. 6,051,146 issued on Apr. 18, 2000. The entire disclosure of this U.S. patent is incorporated herein by reference to the extent it is not inconsistent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods to enhance white blood cell count Inventor(s): Abrams, Michael J.; (Custer, WA), Bridger, Gary; (Bellingham, WA), Henson, Geoffrey W.; (Ferndale, WA), MacFarland, Ronald Trevor; (Vancouver, CA), Millar, Andrew W.; (Wallingford, GB) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20020058653 Date filed: January 4, 2002 Abstract: Methods to elevate white blood cell counts in animal subjects using compounds of formula (1) are disclosed. These compounds have the formulaZ-linker-Z' (1)or pharmaceutically acceptable salt thereofwherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;Z' may be embodied in a form as defined by Z above, or alternatively may be of the formula--N(R)--(CR.sub.2).sub.n--X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;"linker" represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms;in an amount effective to elevate said WBC count in said subject. Excerpt(s): The invention is in the field of therapeutics and medicinal chemistry. More particularly, the invention concerns methods to enhance white blood cell counts in subjects by administering certain cyclic polyamines. White blood cells play a significant part in maintaining the health and viability of animals, including humans. These white blood cells include neutrophils, macrophage, and basophils/mast cells as well the B and T cells of the immune system. White blood cells are continuously replaced (as are red blood cells and clot forming cells) by the hematopoietic system in response to a number of growth factors, such as colony stimulating factors (CSF) and various cytokines. The nucleotide sequences encoding a number of these growth factors have been cloned and sequenced. Perhaps the most widely known of these is granulocyte colony stimulating factor (G-CSF) which has been approved for use in counteracting the negative effects of chemotherapy. A discussion of the hematopoietic effects of this factor can be found, for example, in U.S. Pat. No. 5,582,823, incorporated in its entirety by

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reference herein. While endogenous growth factors are pharmacologically effective, the well known disadvantages of employing proteins and peptides, as opposed to small molecules, as pharmaceuticals underlies the need to add to the repertoire of such growth factors compounds which are themselves small molecules. In another aspect, such small molecules are advantageous over proteins and peptides where production in large quantities are desired. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Multi-purpose reagent system and method for enumeration of red blood cells, white blood cells and thrombocytes and differential determination of white blood cells Inventor(s): Carter II, James Harrison; (Plantation, FL), Crews, Harold Richardson; (Coral Springs, FL), Elliot, Michael Norman; (Fort Lauderdale, FL) Correspondence: Martin Fleit; Fleit Kain Gibbons Gutman & Bongini; 520 Brickell Key Drive #a201; Miami; FL; 33131; US Patent Application Number: 20020098589 Date filed: January 19, 2001 Abstract: A novel reagent system for use with automated and semi-automated hematology analyzers including an essentially isotonic blood diluting reagent, a blood cell lysing and hemoglobin conversion reagent, and a second lysing reagent for differentiating white blood cells into classes by size and functional characteristics. The diluent reagent enhances properties for counting and sizing blood specimens, while stabilizing cellular volume and cellular integrity for many hours. The blood cell lysing reagent removes red blood cells and enables subsequent enumeration of white blood cells and simultaneous determination of hemoglobin without use of the toxic cyanide anion. The third lysing reagent and a companion quenching differentiates blood cells into classes by size and functional characteristics, based on d.c. impedance volume, conductivity/opacity and light scatter measurements. The companion quenching reagent adjusts pH and conductivity of the final measurement solution to match the analyzer system requirements. Novel methods for use of the reagents with automated and semi-automated hematology analyzers are also provided. Excerpt(s): The invention relates to a multi-purpose reagent system and method for enumeration of red blood cells, white blood cells and thrombocytes and differential determination of white blood cells. The art recognizes that the ability to resolve the various populations of blood cells into their constituent classes, particularly those of the leukocytes, provides an invaluable diagnostic aid in the study, diagnosis and treatment of various diseases. As is further appreciated, the greater the number of sub-populations that are identifiable and enumeratable, the more accurate and reliable the identification of any single sub-population is likely to be. Previous scientific publications and patents have described reagents and methods for enumerating these cell types by a variety of mechanisms. U.S. Pat. No. 4,485,175 (to Ledis, et al.) describes a reagent system comprising a multipurpose blood diluent and a lysing reagent, and a method for utilizing same to produce a hemoglobin measurement and differentiation of white blood cells into at least one and up to three sub-populations of leukocytes. U.S. Pat. No. 5,731,206 (to Ledis, et al.) describes a lytic reagent composition, a kit of a lytic reagent system and a method for isolating, identifying and analysis of at least one and up to five sub-populations of leukocytes from a whole blood sample. Other representative patent references pertinent to this field include U.S. Pat. Nos. 3,874,852; 4,286,963; 4,346,018; 4,528,274 and 4,751,179. All are hereby incorporated by reference in their entirety.

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

Nuclear morphology based identification and quantification of white blood cell types using optical bio-disc systems Inventor(s): Gordon, John Francis; (Irvine, CA), Selvan, Gowri Pyapali; (Irvine, CA) Correspondence: Donald Bollella, ESQ.; Chief Patent Counsel; Burstein Technologies, INC.; 163 Technology Drive; Irvine; CA; 92618; US Patent Application Number: 20030113925 Date filed: September 6, 2002 Abstract: The present invention relates in general to biological assays and diagnostic assays and, in particular, to methods and apparatuses for imaging cells using an optical bio-disc system. More specifically, but without restriction to the particular embodiments hereinafter described in accordance with the best mode of practice, this invention relates to methods for identifying and quantitating cells including white blood cells based on the morphology of their nucleus using stains that absorb electromagnetic radiation at pre-determined wavelengths in conjunction with optical bio discs. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/988,728 filed Nov. 20, 2001. This application also claims the benefit of priority from U.S. Provisional Application Serial No. 60/318,026 filed Sep. 7, 2001; No. 60/322,040 filed Sep. 11, 2001; No. 60/322,863 filed Sep. 12, 2001; No. 60/322,527 filed Sep. 14, 2001; No. 60/326,800 filed Oct. 3, 2001; No. 60/353,300 filed Jan. 31, 2002; No. 60/355,644 filed Feb. 5, 2002; No. 60/358,479 filed Feb. 19, 2002; and No. 60/363,949 filed Mar. 12, 2002. These applications are herein incorporated by reference in their entireties. This invention relates in general to biological assays and diagnostic assays and, in particular, to methods and apparatuses for imaging blood cell analytes in biological samples. More specifically, but without restriction to the particular embodiments hereinafter described in accordance with the best mode of practice, this invention relates to methods for identifying and quantitating white blood cells based on the morphology of their nucleus using stains that absorb electromagnetic radiation at pre-determined wavelengths in conjunction with optical bio discs. The present invention may be advantageously employed in combination with any of the discs, assays, and systems disclosed in the following commonly assigned and co-pending patent applications: U.S. Provisional Application Serial No. 60/302,757 entitled "Clinical Diagnostic Optical BioDisc And Related Methods For Selection And Detection Of Lymphocytes Including Helper-Inducer/Suppressor-Cytotoxic Cells" filed Jul. 3, 2001; U.S. Provisional Application Serial No. 60/306,035 entitled "Quantitative and Qualitative Methods for Cell Isolation and Typing Including Immunophenotyping" filed Jul. 17, 2001; U.S. Provisional Application Serial No. 60/305,993 entitled "Capture Layer Assemblies and Optical Bio-Discs for Immunophenotyping" filed Jul. 17, 2001; U.S. Provisional Application Serial No. 60/306,592 entitled "Methods for Imaging Blood Cells, BloodBorne Parasites and Pathogens, and Other Biological Matter Including Related Optical Bio-Discs and Drive Assemblies" filed Jul. 19, 2001; and U.S. Provisional Application Serial No. 60/307,263 entitled "Quantitative and Qualitative Methods for Cell Isolation and Typing Including Immunophenotyping" filed Jul. 23, 2001. All of these applications are herein in incorporated by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Patient-specific white proteoliposomes

blood

cell

malignancy

vaccine

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Inventor(s): Batenjany, Michael M.; (Hamilton, NJ), Boni, Lawrence; (Monmouth Junction, NJ), Popescu, Mircea C.; (Plainsboro, NJ), Robb, Richard J.; (Princeton Junction, NJ) Correspondence: Bernhard D. Saxe; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20010012517 Date filed: March 26, 2001 Abstract: Membrane-proteoliposome structures (MPs) are useful in preparing patientspecific vaccines against specific white blood cell (WBC) malignancies. The inventive MPs typically contain a membrane component derived from a specific WBC. Other useful components include immunostimulators and exogenous lipids. The resulting vaccines are both patient- and malignancy-specific. Excerpt(s): The present invention is directed to the production of novel compositions, useful as vaccines for treating white blood cell (WBC) malignancies. The invention relates to a liposomal, patient-specific vaccine comprised of WBC membranes that may be formulated by adding other lipids and/or immunostimulators, thereby forming a novel membrane-proteoliposome (MP) structure. Known vaccines typically utilize either purified antigen or attenuated pathogen as the immunogen. However, attenuated vaccines can actually cause the infection against which a person is being immunized. On the other hand, purified antigens may not induce a long-term immune response and sometimes induce no response at all. In contrast to the short-term immune response obtained by direct immunization with certain antigens, presentation of the antigen in the presence of liposomes can induce a long-term response which is essential for any effective vaccine. Although typically formed from purified or partially purified lipids, liposomes may also be formed, at least in part, from cell membranes of malignant cells which contain potential antigens. Due to the presence of membrane associated antigens, these membrane-derived preparations may be used as malignancy-specific vaccines. Indeed, some types of membrane-derived preparations have been used as tumor specific antigens (TSA) to treat melanomas and murine SL2 lymphosarcoma. See Gershman et al., Vaccine Res. 3:83-92 (1994); Bergers et al., J. Confr. Rel. 29:317-27 (1994); Bergers et al., J. Liposome Res. 6:339-35 (1996). In these cases, the production of vaccine suffered from serious disadvantages. Namely, they required pooling culture adapted cells to achieve large amounts of the desired cell populations, use of whole.gamma.-irradiated tumor cells, detergent solubilization or butanol for crude extraction of tumor-associated antigens (TAA). See Gershman et al. (1994), supra; Abbas, et al., CELLULAR AND MOLECULAR IMMUNOLOGY, pp.372-73 (W. B. Saunders Company, Philadelphia 1994); Bergers et al. (1994), supra; LeGrue et al., J. Natl. Cancer Inst. 65:191-96 (1980). This approach, moreover, is not patient-specific. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Preserving a hemoglobin blood substitute with a transparent overwrap Inventor(s): Gawryl, Maria S.; (Charlestown, MA), Houtchens, Robert A.; (Milford, MA), Light, William R.; (Natick, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20020128182 Date filed: July 24, 2001 Abstract: The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The invention also involves a method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulent to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavenges oxygen, to form a stable polymerized hemoglobin bloodsubstitute, which is then packaged and stored in an atmosphere substantially free of oxygen. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/348,881, filed on Jul. 7, 1999, which is a continuation-in-part of U.S. Ser. No. 09/173,189, filed on Oct. 14, 1998, which is a continuation-in-part of U.S. Ser. No. 08/974,658, filed on Nov. 19, 1997, now abandoned, which is a continuation of U.S. Ser. No. 08/471,583, filed on Jun. 7, 1995, now issued U.S. Pat. No. 5,691,452, which is a continuation-in-part of U.S. Ser. No. 08/458,916, filed on Jun. 2, 1995, now issued U.S. Pat. No. 5,840,582, which is a continuation of U.S. Ser. No. 08/409,337, filed on Mar. 23, 1995, now issued U.S. Pat. No. 5,854,209. The entire teachings of the above applications are incorporated herein by reference. There exists a need for a blood-substitute to treat or prevent hypoxia resulting from blood loss (e.g, from acute hemorrhage or during surgical operations), resulting from anemia (e.g., pernicious anemia or sickle cell anemia), or resulting from shock (e.g, volume deficiency shock, anaphylactic shock, septic shock or allergic shock). The use of blood and blood fractions as in these capacities as a blood-substitute is fraught with disadvantages. For example, the use of whole blood often is accompanied by the risk of transmission of hepatitis-producing viruses and AIDS-producing viruses which can complicate patient recovery or result in patient fatalities. Additionally, the use of whole blood requires blood-typing and cross-matching to avoid immunohematological problems and interdonor incompatibility. Human hemoglobin, as a blood-substitute, possesses osmotic activity and the ability to transport and transfer oxygen, but it has the disadvantage of rapid elimination from circulation by the renal route and through vascular walls, resulting in a very short, and therefore, a typically unsatisfactory halflife. Further, human hemoglobin is also frequently contaminated with toxic levels of endotoxins, bacteria and/or viruses.

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

Transmembrane polypeptide expressed by lymphocytes Inventor(s): Haldeman, Betty A.; (Seattle, WA), Holly, Richard D.; (Seattle, WA), Sheppard, Paul O.; (Granite Falls, WA) Correspondence: Phillip B.C. Jones, J.D., PH.D.; Patent Department; Zymogenetics, INC.; 1201 Eastlake Avenue East; Seattle; WA; 98102; US Patent Application Number: 20020164764 Date filed: October 18, 2001 Abstract: White blood cells protect the body by inactivating and destroying foreign agents, including tumor cells. The specificity of the immune response is mediated by lymphocytes. Lymphocytes express certain transmembrane proteins on their cell surfaces that distinguish between normal lymphocyte cell types, as well as between normal and cancerous cells. These lymphocyte "markers" are used for diagnosis, prognosis, and therapy. Zsig16 is a new transmembrane protein that is expressed by human peripheral blood lymphocytes. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/394,767 (filed Sep. 13, 1999), which claims the benefit of U.S. Provisional application No. 60/100,865 (filed Sep. 17, 1998), the contents of which are incorporated by reference. The present invention relates generally to a novel polypeptide, designated as "Zsig16," which is expressed by human peripheral blood lymphocytes. In particular, the present invention relates to nucleic acid molecules encoding Zsig16, and the use of such nucleic acid molecules and Zsig16 polypeptides. An immune response to a foreign agent involves recognition of a foreign antigen, and the production of a reaction against the foreign material to eliminate it from the body. For a review, see Roitt et al., Immunology, 4.sup.th Edition (Mosby 1996), Walsh, Biopharmaceuticals: Biochemistry and Biotechnology (John Wiley & Sons 1998). White blood cells, or "leukocytes," constitute the cells of the immune system, and function to protect the body by inactivating and destroying foreign agents, including tumor cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment for inflammatory bowel disease with a fibronectin polypeptide Inventor(s): Burkly, Linda C.; (West Newton, MA), Lobb, Roy R.; (Westwood, MA) Correspondence: Louis Myers; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20030095969 Date filed: September 23, 2002 Abstract: A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut. Excerpt(s): This application is a continuation-in-part of Lobb U.S. Ser. No. 08/373,857, filed Jan. 18, 1995, which is a continuation-in-part of Lobb U.S. Ser. No. 08/284,603, filed Aug. 11, 1994, and of PCT/US93/00924 filed Feb. 2, 1993, which is the continuation-in-

Patents 171

part of Lobb U.S. Ser. No. 07/835,139, filed Feb. 12, 1992, all of which are incorporated by reference. The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4 ) in the treatment of EBD. Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups. 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 white blood cells, 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 “white blood cells” (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 white blood cells. You can also use this procedure to view pending patent applications concerning white blood cells. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON WHITE BLOOD CELLS Overview This chapter provides bibliographic book references relating to white blood cells. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on white blood cells 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: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “white blood cells” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “white blood cells” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “white blood cells” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

The Odyssey: The Pulsating Voyage & Adventures of White Blood Cell by Caspian Ashworth, Neil Ashworth (Illustrator) (2001); ISBN: 1857766709; http://www.amazon.com/exec/obidos/ASIN/1857766709/icongroupinterna

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Total White Blood Cell Counts for Persons Ages 1-74 Years with Differential Leukocyte Counts for Adu: United States, 1971-1975 by Cornelia R. McGrath (1982); ISBN: 0840602022; http://www.amazon.com/exec/obidos/ASIN/0840602022/icongroupinterna

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White Blood Cells: Morphology and Rheology As Related to Function by U. Bagge (Editor) (1982); ISBN: 9024726816; http://www.amazon.com/exec/obidos/ASIN/9024726816/icongroupinterna

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

Blood Dyscrasias Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 495-515. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340. Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This chapter on blood dyscrasias is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. The authors of this chapter focus on the most common disorders of the red and white blood cells that may influence dental treatment. Patients with these disorders may be susceptible to abnormal bleeding, delayed healing, infection, or mucosal ulceration. In addition, the dentist can play a vital role in screening patients who may not be aware that they have one of these potentially fatal conditions. The authors cover anemia (including sickle cell and iron deficiency types), and white blood cell disorders (leukopenia, leukemia, lymphomas, myeloma). For each condition, the authors discuss incidence and prevalence, pathophysiology and complications, signs and symptoms (clinical presentation and laboratory findings), the medical management of patients with the specific condition, and the dental management of this population, including expected oral complications associated with each disorder and treatment planning considerations. 9 figures. 14 tables. 38 references.

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Principles of Hemodialysis Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 35-45. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: Dialysis, the process of cleansing the blood of accumulated waste products, is a complex treatment requiring a team of highly trained individuals with a variety of skills. This chapter on the principles of hemodialysis is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The author of the chapter begins with a brief

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history of the use of dialysis in medicine, then discusses solute transfer, transport, ultrafiltration, and the quantification of dialysis. In hemodialysis, metabolic wastes or toxins are filtered from the blood by a semipermeable membrane and carried away by the dialysis fluid. The semipermeable membrane acts as a sieve; the patient's blood is passed through a compartment formed by the membrane. Dialyzing fluid surrounds this compartment. Red blood cells, white blood cells, platelets, and most plasma proteins are too large to pass through the pores of the membrane. Water and small particles such as electrolytes cross by diffusion (transport), as do urea, creatinine, and glucose. This process is measured by clearance, an empirical measure indicating a calculated volume of blood completely cleared of a substance (x) in 1 minute. The author explains how this concept is used with hemodialyzers and reviews the use of the urea Kt per V index to determine dialysis adequacy. •

Eosinophilic Gastroenteritis Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1972-1982. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Eosinophilic gastroenteritis is a disease characterized by tissue eosinophilia (an increase in a type of white blood cells) that can involve any layer or layers of the gut wall. This chapter on eosinophilic gastroenteritis is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include definition and incidence; pathogenesis; classification and clinical features; diagnostic considerations; differential diagnosis; treatment options, including diet, antihelminthics, sodium cromoglycate, glucocorticoids and immunosuppressive agents, and surgery; and prognosis. The chapter includes a mini-outline with page citations, illustrations, and extensive references. 4 figures. 1 table. 100 references.

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Laboratory Tests Source: in Lockhart, P.B. Oral Medicine and Hospital Practice. Chicago, IL: Special Care Dentistry. 1997. p. 10.3-10.12. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. PRICE: $27.00 (member) or $30.00 (nonmember), plus shipping and handling; institutional prices and bulk orders available. ISBN: 0965719103. Summary: This chapter is from a manual designed to help dental residents, students and practitioners engaged in the care of patients in the hospital setting. This chapter presents information on common laboratory tests. The chapter describes hematology, including complete blood count (CBC), sickle cell tests, and coagulation tests; blood chemistry, including total protein, calcium, phosphorus, cholesterol, glucose, uric acid, creatinine, phosphatase, and transaminases; other blood determinations, including blood urea nitrogen (BUN), bilirubin, creatine phosphokinase (CPK or CK), serum iron, total iron binding capacity (TIBC), serum osmolality, glucose tolerance test (GTT), triglycerides, and electrolytes; thyroid testing, including hormones and radioactive iodine (RAI) uptake test; urinalysis, including color, odor, specific gravity, chemical examination, and microscopic examination; cerebrospinal fluid, including glucose, protein, white blood

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cells, and red blood cells; and arterial blood gases. For each test, the author notes the expected normal value, the significance of high or low values, and the relevant oral findings. Most information is presented in outline format, for ease of access. 1 table. •

Useful Biologic Markers as Activity Indices Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 35-38. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on interpreting symptoms is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). The author stresses that the accurate assessment of clinical disease activity in IBD is critical to appropriate and effective patient care. It can be difficult to differentiate between a worsening of the IBD and other factors (medication, infection, food, emotional stress), both of which can lead to worsening diarrhea, abdominal pain, malaise, and fatigue. The availability of an accurate, rapid, easy to perform, and affordable biologic parameter (measure) of disease activity would be invaluable to physicians caring for IBD patients. Unfortunately, such a test does not currently exist. Despite the increasing knowledge of the pathophysiology of intestinal inflammation, physicians do not yet know all of the factors that control the worsening or improving of disease symptoms. Until the signals that initiate and accompany a flare of UC or CD can be fully identified, physicians must still rely on clinical skills and nonspecific markers of inflammation to assess disease activity. Despite their subjective components, clinical indices remain the mainstay for assessing disease activity in clinical trials. For the practicing physician, the addition of CRP (C reactive protein) and orosomucoid (a glycoprotein), if available, or ESR (erythrocyte sedimentation rate) can be useful to support the diagnosis of a disease flare. A quantitative assessment of leukocyte (white blood cells) excretion in the stool, if standardized, rapid, and easy to perform, would likely provide an adjunctive objective measure of intestinal inflammation. 1 table. 14 references.

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Chapter 53: Bone and Joint Infections Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 5 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have bone and joint infections with information on the causes, symptoms, diagnosis, and treatment of osteomyelitis and infectious arthritis. Osteomyelitis is a bone infection usually caused by bacteria and sometimes by a fungus. Bones can become infected as a result of an infection carried by the bloodstream from another part of the body to the bones, organisms invading the bone directly, and an adjacent soft tissue infection. Symptoms include pain and swelling of the area over the bone. Diagnosis is based on symptoms and findings from a physical examination; diagnostic imaging studies; and tests on samples of blood, pus, joint fluid, or the bone itself. Antibiotics are the most effective

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treatment for bone infections contracted through the bloodstream. Treatment is more complex when a bone infection results from an adjacent soft tissue infection. The usual course of treatment is surgical removal of all the dead tissue and bone followed by packing of the empty space with healthy bone, muscle, or skin. Infectious arthritis, another type of infection, involves the synovial fluid and tissues of a joint. Bacteria are the main infecting organisms. Joint infection can occur through the bloodstream or through direct means. Viruses can also infect joints in people of any age. Symptoms of joint infections in infants include fever, pain, and fussiness. In older children and adults, symptoms include redness and warmth, painful movement, swelling, and stiffness. If an infection is suspected, several diagnostic tests are performed, including examination of a joint fluid sample for white blood cells and bacteria and other organisms. Antibiotic treatment is started as soon as an infection is suspected because an infected joint can be destroyed within days if antibiotic treatment is not started promptly. Pus may be removed with a needle. Infections caused by fungi are treated with antifungal drugs, but viral infections require treatment only for pain and fever. •

Hematologic Disease Source: in Clinician's Guide to Treatment of Medically Compromised Patients. Baltimore, MD: American Academy of Oral Medicine (AAOM). 1995. p. 45-56. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This chapter, from a guide for dentists on managing problems of medically compromised dental patients, discusses patients with hematologic disease. The authors provide a summary of the disorders involving the cellular elements of the bone marrow, including diseases of the white blood cells; platelet disorders; anemia; other bleeding disorders; and hepatitis. For each condition covered, topics covered include a definition, the etiology, clinical findings and symptoms, diagnostic tests, therapy, and dental management considerations. The majority of the information is presented in chart format.

•

Urinary Tract Infections Source: in Schena, F.P., ed. Nephrology. New York, NY: McGraw-Hill, Inc. 2001. p. 283291. Contact: Available from McGraw-Hill, Inc. Shoppenhangers Road, Maidenhead, Berkshire SL6 2QL. 44 (0)1628 502700. Fax: +44 (0)1628 635895 E-mail: [email protected]. Website: www.mcgraw-hill.co.uk. PRICE: $79.95; plus shipping and handling. ISBN: 0077095251. Summary: Urinary tract infections (UTIs) represent more than 50,000 diagnoses per million people per year and more than 2 percent of the activity of general practitioners (in Europe). This chapter on UTIs is from a book on nephrology (the study of the kidney and kidney diseases) designed for general practitioners and family care providers that offers strategies for the management of patients with renal (kidney) damage. Diagnosis of UTI is based on the presence of a significant number of bacteria and leukocytes (white blood cells) in a midstream urine analysis. A clear distinction should be make between cystitis (bladder infection) in the female, which is a superficial mucosal inflammation, and infection of a full organ, that is pyelonephritis (kidney infection) in either gender, and prostatitis (inflammation or infection of the prostate) in the male. The uropathogenicity (ability to cause urinary tract disease) of urinary bacteria plays a major

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role when pyelonephritis occurs in an anatomically sound urinary tract. Imaging tests should be limited in simple pyelonephritis in the female and extensive in the male and in children, in whom a urologic (anatomical, usually) cause is often responsible for UTI. Treatment is limited to 4 day monotherapy in female cystitis (European guidelines). Protracted, combined therapy with adapted antimicrobial agents is mandatory in full organ involvement and in patients with compromised immune systems. The chapter includes a brief discussion of special situations, including pyelonephritis in pregnancy, in people with diabetes, in older patients, and in patients with long term indwelling urinary catheters. 3 tables. 15 references.

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CHAPTER 8. MULTIMEDIA ON WHITE BLOOD CELLS Overview In this chapter, we show you how to keep current on multimedia sources of information on white blood cells. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on white blood cells is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “white blood cells” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “white blood cells” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on white blood cells: •

Protection Against Infection: Inside Story of the Immune System and AIDS Contact: Agency for Instructional Technology, Box A, Bloomington, IN, 47402, (812) 3392203. Summary: In this videorecording, Slim Goodbody (John Burstein) of the Captain Kangaroo children's television program, explains to primary and intermediate school students how the body's immune system provides "protection against infection." Surrounded by giant models of red and white blood cells, he describes how the immune system fights infection, and that Acquired immunodeficiency syndrome (AIDS) is a killer because it destroys the immune system itself. Slim Goodbody is shown answering questions about AIDS from a group of children at a playground, and delivering his health message in two songs, "Be Your Own Best Friend" and "Defense, Defense." He reassures children who ask about sitting next to someone with AIDS, kissing, insect bites, and being sneezed on that casual contact does not transmit the Human immunodeficiency virus (HIV). A scene of a mother, a father, and an infant leads to a discussion of how HIV is transmitted, primarily by sexual intercourse or

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infected IV needles employed in illegal drug use. He tells the children that now, before their bodies mature, is the best time to learn how to protect themselves against AIDS. "Your bodies are your own," he says, commenting that they could some day be pressured toward sexual activity before they are adults. His closing message is "You have the power to keep your body safe.". •

Your Biological Guide to AIDS Contact: British Broadcasting Corporation, Enterprises Limited, Woodlands. Summary: This program, hosted by Alan Maryon Davis, Graeme Garden, and Gillian Rice, provides the viewer with facts about Acquired immunodeficiency syndrome (AIDS), including a description of risk behaviors, preventive measures such as condom use and the avoidance of IV drugs, treatment, and problems with development of a vaccine. An animated segment on Human immunodeficiency virus (HIV) infection and the attack of the virus on white blood cells is presented.

•

What Is AIDS? Contact: Coronet/MTI Film and Video, 108 Wilmot Rd, Deerfield, IL, 60015-9925, (708) 940-1260. Summary: This video gives basic information about the acquired immunodeficiency syndrome (AIDS) to children ages 6 to 12. The film uses the analogy of a baseball game to compare the body's immune system to a team defending itself against germs. A second analogy likens the body to a house and the white blood cells act as security guards. It emphasizes that by observing appropriate behavior, children should not fear contracting the human immunodeficiency virus (HIV) by persons with AIDS (PWA's).

•

The Body Fights Disease Contact: Churchill Media, 6677 North NW Hwy, Chicago, IL, 60631, (773) 775-9550. Summary: This video provides secondary-school students with an introduction to the human immune system. Largely animated segments portray the role of white blood cells, lymphocytes, and antibodies in protecting the body against infections. The videorecording explains how the acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), attacks the immune system and leaves the body vulnerable to potentially fatal infections.

•

AIDS Vision: HIV and Vision Loss Contact: Center for the Partially Sighted, HIV and Vision Loss Program, 12301 Wilshire Blvd Ste 600, Santa Monica, CA, 90025, (310) 458-3501, http://www.low-vision.org. Summary: This videorecording discusses where to go and what to do about HIV and vision loss. It uses a question-and-answer format, featuring host and guest experts to discuss CMV retinitis, opportunistic infections such as toxoplasmosis and herpes, and central nervous system infections as causes of HIV-related vision loss. It discusses the most common symptom of HIV-related vision loss, an increase in liberated white blood cells seen as little black dots and known as floaters and cover medications used for effective treatment. The videorecording highlights equipment for managing vision loss on a daily basis. Glasses, microscopes, telescopes, talking clocks and calculators, large print texts, and closed circuit magnifiers are demonstrated. It focuses on the services proved by the Center for the Partially Sighted. They include vision evaluation, assistance with goal setting, and initiating independent living for HIV-infected clients. It

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stresses the Center's ability to match services with client needs. Home visits, psychological counseling, and mobility and access training are featured. An address and phone number are provided for more information.

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CHAPTER 9. PERIODICALS AND NEWS ON WHITE BLOOD CELLS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover white blood cells.

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

Stem cells prepped from white blood cells Source: Reuters Health eLine Date: November 27, 2003

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•

White blood cells tied to cancer survival gap Source: Reuters Health eLine Date: October 17, 2003 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 “white blood cells” (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 “white blood cells” (or synonyms). If you know the name of a company that is relevant to white blood cells, 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 “white blood cells” (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 “white blood cells” (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 white blood cells: •

What Blood Tests Tell Us Source: Harvard Women's Health Watch. 7(3): 6. November 1999. Contact: Available from Harvard Women's Health Watch. P.O. Box 420068, Palm Coast, FL 32142-0068. (800) 829-5921 or (904) 445-4662. Summary: This brief newsletter article describes the standard blood tests that may be done to diagnose disease or monitor risk factors. The author uses the metaphor of the bloodstream as a river that brings oxygen and other vital nutrients to the body's cells and carries waste away from them. This 'river' also transports the cellular and molecular forces that fight disease, and ferries hormones from the glands to the tissues. By sampling this stream, doctors can identify elevated risk in people who are healthy and pick up clues to the sources of symptoms in those who are sick. The few cubic centimeters of blood contain millions of cells and molecules, each of which can vary in number according to the person's state of health. The lab report resulting from a blood test usually consists of two sections: hematology, which provides information about blood cells, and chemistry, which furnishes data about plasma. The bulk of the article consists of a chart that explains the results of a typical blood test. The chart lists the lab values typically studied, the range of results considered normal, and the significance of values outside the normal range. Lab values included are WBC (white blood cells), HCT (hematocrit), PLT (platelets), CHOL (total cholesterol), HDL ('good' cholesterol), LDL ('bad' cholesterol), TRIG (triglycerides), BUN (blood urea nitrogen), CREAT (creatinine), GLU (glucose), and TSH (thyroid stimulating hormone). 1 table.

•

Sarcoidosis Source: Sarcoidosis Networking. 2-3; September/October 1997. Contact: Pacific Northwest Sarcoid Association, Sarcoid Networking Association, 13925 80th Street East, Puyallup, WA 98372-3614. (253) 845-3108. (253) 845-3108 (fax). Summary: This newsletter article for individuals with sarcoidosis presents an overview of this disease. Sarcoidosis spreads white blood cells throughout the body, and they clump together and form a mass known as granuloma. A granuloma that grows large enough may then block the function of any body tissue. The article describes the symptoms of sarcoidosis, presents the techniques used to diagnosis sarcoidosis, identifies the drugs used to treat the symptoms of sarcoidosis, and highlights the side effects of these drugs. 16 references.

•

Bad Teeth and Gums a Risk Factor for Heart Disease? Source: Harvard Heart Letter. 9(3): 6-7. November 1998.

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Contact: Available from Harvard Heart Letter. P.O. Box 420379, Palm Coast, FL 321420379. (800) 829-9171. E-mail: [email protected]. Website: www.countway.harvard.edu/publications/Health_Publications. Summary: This newsletter article informs readers about recent studies that are investigating the role of bad teeth and gums as risk factors for heart disease. Several studies found that patients with heart disease had more tooth decay and higher rates of gum disease. A link between oral health and heart disease was also found in epidemiological studies that examined people's teeth and then followed them for several years to see if those with poor dental health were more likely to get heart disease. For example, people with inflammation of the gums (periodontitis) had a 25 percent increased risk of heart disease over the follow up period, compared to those with minimal periodontitis. The author notes that one reason why many scientists have been skeptical about poor dental health as a cause of heart disease is that there was no obvious way in which the two conditions could be linked. Some experts now speculate that the bacteria that accumulate in the gums and teeth of people with poor dental hygiene cause inflammation that leads to an increase in blood clotting factors. If so, these clotting factors might increase the chances that a blood clot could form in the heart. Another theory considers the role of white blood cells that fight infection in the gums and elsewhere. The author concludes that these theories sound promising, but at present remain unproven. •

Importance of Proper Dental Care for Head and Neck Cancer Patients Source: News from SPOHNC. News from Support for People with Oral and Head and Neck Cancer, Inc. 10(5): 1-3. February 2001. Contact: Available from Support for People with Oral and Head and Neck Cancer, Inc. (SPOHNC). P.O. Box 53, Locust Valley, NY 11560-0053. (516) 759-5333. E-mail: [email protected]. Website: www.spohnc.org. Summary: This newsletter article reviews the importance of proper dental care for head and neck cancer patients. The author stresses that the oral cavity is invariably compromised as a result of treatment for head and neck cancer. Whether the malignancy (cancer) is to be treated by surgery, radiation therapy, chemotherapy, or a combination of these modalities, the function, if not also the form, of the oral cavity will be affected. The most common and profound side effects of irradiation to the head and neck region are: dry mouth (xerostomia), post irradiation dental caries (cavities), the risk of osteoradionecrosis (non healing, chronic bone death in irradiated bone that has a compromised blood supply), and trismus (inability to open the mouth fully). The author discusses each of these side effects and offers strategies for prevention and treatment. The author then discusses chemotherapy, reporting on the possible side effects including oral lesions and low levels of blood platelets and white blood cells (responsible for clotting and fighting infection, respectively). The author concludes with suggestions for locating dental specialists to provide care before, during and after cancer therapy.

Academic Periodicals covering White Blood Cells Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to white blood cells. In addition to these sources, you can search for articles covering white blood cells that have been

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published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. 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 white blood cells. 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 white blood cells. 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.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to white blood cells: Aldesleukin •

Systemic - U.S. Brands: Proleukin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202669.html

Anti-Thymocyte Globulin (Rabbit) •

Systemic - U.S. Brands: Thymoglobulin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500099.html

Basiliximab •

Systemic - U.S. Brands: Simulect http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203592.html

Colony Stimulating Factors •

Systemic - U.S. Brands: Leukine; Neupogen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202628.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html

Daclizumab •

Systemic - U.S. Brands: Zenapax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203435.html

Denileukin Diftitox •

Systemic - U.S. Brands: Ontak http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500010.html

Imatinib •

Systemic - U.S. Brands: Gleevec http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500297.html

Lithium •

Systemic - U.S. Brands: Cibalith-S; Eskalith; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202330.html

Methoxsalen •

Extracorporeal-Systemic - U.S. Brands: Uvadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500002.html

•

Systemic - U.S. Brands: 8-MOP; Oxsoralen-Ultra http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202357.html

Mycophenolate •

Systemic - U.S. Brands: CellCept http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203436.html

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Sirolimus •

Systemic - U.S. Brands: Rapamune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500028.html

Tacrolimus •

Systemic - U.S. Brands: Prograf http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202914.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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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute8: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

8

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

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

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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

•

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/

•

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.9 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:10 •

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

•

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

•

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

•

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

•

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

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

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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

•

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

9

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). 10 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “white blood cells” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “white blood cells” (or synonyms) into the “For these words:” box. The following is a sample result: •

AIDS - Related Cryptococcal Meningitis Contact: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Allergy and Infectious Diseases, 31 Center Dr MSC 2520, Bethesda, MD, 20892-2520, (301) 496-5717, http://www.niaid.nih.gov. Summary: This report describes cryptococcal meningitis that is related to Acquired immunodeficiency syndrome (AIDS). It says that cryptococcal disease accounts for 5-8 percent of all opportunistic infections, and that it is caused by cryptococcus neoformans, a yeastlike fungus found in soil contaminated with bird excrement. Exposure is quite common, but it only manifests as a disease in those individuals with compromised immune systems. The fungus may infect numerous organs, particularly the skin, lungs, and meninges. As meningitis, it has the following symptoms: Fever, headache, fatigue, nausea, and vomiting. It may also cause changes in behavior or personality, memory loss or confusion, and difficulty with coordination. Unless maintenance therapy continues, the relapse rate after initial treatment is 50-90 percent. Standard treatment consists of Amphotericin B intravenously for 10 weeks, possibly combined with oral flucytosine. Side effects may include kidney damage, high fever, severe chills, low blood pressure, a decrease in potassium levels, and depressed levels of red and white blood cells, and platelets. Another drug called fluconazole was recently approved for oral or intravenous use, and one called SCH 39304 is under study. At present, the National Institute of Allergy and Infectious Diseases (NIAID) has four meningitis clinical trials underway.

The NLM Gateway11 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,

11

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

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providing one-stop searching for many of NLM’s information resources or databases.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “white blood cells” (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 418118 479 1196 254 0 420047

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “white blood cells” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists16 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.17 Each report is about 400 words and is usually based on a discovery reported in one or

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14

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

15

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. 16 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 17

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.

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more articles from recently published, peer-reviewed literature.18 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/.

18

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

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

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•

Other guides Anemia http://www.nlm.nih.gov/medlineplus/anemia.html Blood and Blood Disorders http://www.nlm.nih.gov/medlineplus/bloodandblooddisorders.html Blood Transfusion and Donation http://www.nlm.nih.gov/medlineplus/bloodtransfusionanddonation.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 white blood cells. 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: •

Low White Blood Cell Count Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses low white blood cell count. White blood cells, or leukocytes, are those cells that the human body produces to help to fight infections. The two most common types of white blood cells are lymphocytes and neutrophils. Lymphocytes are made in the spleen, lymph nodes, and thymus gland. These cells identify foreign substances from bacteria or viruses in the body and produce antibodies to target them. Neutrophils are made in bone marrow and enter infected tissue to attack the bacteria. Prescription medications used to treat some of the more common opportunistic infections among HIV-positive individuals such as Kaposi's sarcoma or infections of the bone marrow or that block the production of chemicals can cause a low neutrophil count or neutropenia. A low netrophil count is diagnosed by a blood test called a complete blood count or through a bone marrow aspiration. Treatment of neutropenia requires identifying and remedying its cause.

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to white blood cells. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to white blood cells. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with white blood cells. 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 white blood cells. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at

204 White Blood Cells

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 “white blood cells” (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 “white blood cells”. 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 “white blood cells” (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 “white blood cells” (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.19

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

19

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)20: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

20

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

208 White Blood Cells

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

210 White Blood Cells

•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

•

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

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WHITE BLOOD CELLS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abacavir: A nucleoside analog reverse transcriptase inhibitor (NARTIs) developed by Glaxo Wellcome. [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] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [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] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH]

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Actin: Essential component of the cell skeleton. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]

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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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] 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] Air Pollutants: Substances which pollute the air. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic,

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and immunosuppressant actions. They have also been used as components in poison gases. [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] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily. [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] 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] 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] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] 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]

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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] 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 organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [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] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH]

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Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemia, Sickle Cell: A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [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]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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

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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] Antidepressant: A drug used to treat depression. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] 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] Anti-infective: An agent that so acts. [EU] 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the

220 White Blood Cells

movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [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] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the

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leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arenavirus: The only genus in the family Arenaviridae. It contains two groups LCM-Lassa complex viruses and Tacaribe complex viruses, which are distinguished by antigenic relationships and geographic distribution. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] 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] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascitic Fluid: The serous fluid which accumulates in the peritoneal cavity in ascites. [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] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU]

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Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] 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] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autophagocytosis: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of lysosomes containing cellular components in the process of digestion; it plays an important role in metamorphosis of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [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 Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH]

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Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] 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] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [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] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH]

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Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] 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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bismuth Subsalicylate: A nonprescription medicine such as Pepto-Bismol. Used to treat diarrhea, heartburn, indigestion, and nausea. It is also part of the treatment for ulcers caused by the bacterium Helicobacter pylori (HELL-uh-koh-BAK-tur py-LOH-ree). [NIH] 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] Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of

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capillary and platelet function. [NIH] Blood Banks: Centers for collecting, characterizing, and storing human blood. [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 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 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] Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] 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] 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 aspiration: The removal of a small sample of bone marrow (usually from the hip) through a needle for examination under a microscope. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small

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amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breath Tests: Any tests done on exhaled air. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] 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] Bronchiectasis: Persistent abnormal dilatation 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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Butylated Hydroxyanisole: Mixture of 2- and 3-tert-butyl-4-methoxyphenols that is used as an antioxidant in foods, cosmetics, and pharmaceuticals. [NIH] Butylated Hydroxytoluene: Antioxidant used in foods, cosmetics, petroleum products, etc. It may inhibit some neoplasms and facilitate others. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes

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smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] 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 Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] 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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group

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of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [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] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] 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] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH]

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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] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [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 Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions

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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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular Structures: Components of a cell. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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]

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Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangiography: Radiographic examination of the bile ducts. [NIH] Cholecystography: Radiography of the gallbladder after ingestion of a contrast medium. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]

Chorion: The outermost extraembryonic membrane. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] 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 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] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear

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to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [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] 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] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coal Tar: A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Coke: A residue of coal, left after dry (destructive) distillation, used as a fuel. [NIH] Colitis: Inflammation of the colon. [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,

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hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement 1: The first complement component to act in the cytolysis reaction. It is a trimolecular complex held together with Ca ions and, when activated, has esterase activity which initiates the next step in the sequence. [NIH] Complement 1 Inactivators: Compounds which inhibit, antagonize, or inactivate complement 1. A well-known inhibitor is a serum glycoprotein believed to be alpha-2neuroaminoglycoprotein. It inhibits the activated (esterase) form of complement 1 as well as kinin-forming, coagulation, and fibrinolytic systems. Deficiency of this inactivator has been found in patients with hereditary angioneurotic edema. These compounds are members of the serpin superfamily. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in

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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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] 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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] 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

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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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] 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] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments,

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etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] 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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH]

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Cryptococcus: A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium. [NIH]

Cryptococcus neoformans: A species of the fungus Cryptococcus, which causes cryptococcosis. Its teleomorph is Filobasidiella neoformans. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [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]

Cystitis: Inflammation of the urinary bladder. [EU] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytogenetic Analysis: Examination of chromosomes to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, karyotyping is performed and/or the specific chromosomes are analyzed. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood 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]

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Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] 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] 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.

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[NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentists: Individuals licensed to practice dentistry. [NIH] 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] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [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] Dermal: Pertaining to or coming from the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [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] Diapedesis: The emigration of leucocytes across the endothelium. [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

240 White Blood Cells

aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] 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]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration

Dictionary 241

in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosimeter: In nuclear science and radiotherapy, a device used for the detection and measurement of radiation absorbed dose or any dose-related ionizing radiation received by the individual; a radiation meter intended to measure absorbed dose. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing

242 White Blood Cells

blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Dysgenesis: Defective development. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dysuria: Painful or difficult urination. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [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]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH]

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Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] 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 medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] 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

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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] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [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] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] 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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi

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and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte 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] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist

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that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [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] Exhaustion: The feeling of weariness of mind and 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] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [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] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Circulation: Diversion of blood flow through a circuit located outside the body but continuous with the bodily circulation. [NIH] Extraction: The process or act of pulling or drawing out. [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,

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characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fecal occult blood test: A test to check for blood in stool. (Fecal refers to stool; occult means hidden.) [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] 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] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Hemoglobin: The major component of hemoglobin in the fetus. This hemoglobin has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by leukemia and several types of anemia. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] 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] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The

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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] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flank Pain: Pain emanating from below the ribs and above the ilium. [NIH] 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] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [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.

Dictionary 249

It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosidases: A family of galactoside hydrolases that hydrolyze compounds with an Ogalactosyl linkage. EC 3.2.1.-. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [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] 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]

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Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Neoplasms: Tumors or cancer of the gastrointestinal system. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

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

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic 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 Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. [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] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of

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waste products in the form of urine, or both. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [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] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose 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]

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Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-. [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]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] 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] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer

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of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Cocci: Coccus-shaped bacteria that retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [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] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haematology: The science of the blood, its nature, functions, and diseases. [NIH] 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] 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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent

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headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] 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. [NIH]

Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helminthiasis: Infestation with parasitic worms of the helminth class. [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] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [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] 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

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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] Hemoglobin E: An abnormal hemoglobin that results from the substitution of lysine for glutamic acid at position 26 of the beta chain. It is most frequently observed in southeast Asian populations. [NIH] Hemoglobin H: An abnormal hemoglobin composed of four beta chains. It is caused by the reduced synthesis of the alpha chain. This abnormality results in alpha-thalassemia. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Hepatomegaly: Enlargement of the liver. [NIH]

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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] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH]

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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] 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]

Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] 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] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersplenism: Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH]

258 White Blood Cells

Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [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] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileum: The lower end of the small intestine. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Image Cytometry: A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue

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(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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort Tlymphocytes into subsets based on CD antigens by the technique of flow cytometry. [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] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] 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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH]

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Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU]

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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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well

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as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intravenous pyelography: IVP. X-ray study of the kidneys, ureters, and bladder. The x-rays are taken after a dye is injected into a blood vessel. The dye is concentrated in the urine, which outlines the kidneys, ureters, and bladder on the x-rays. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [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] Iodipamide: A water-soluble radiographic contrast media for cholecystography and intravenous cholangiography. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a

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net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [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] Islet: Cell producing insulin in pancreas. [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 Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [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]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH]

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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] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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 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] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lead Poisoning: Disease caused by the gradual accumulation of a significant body burden of lead. [NIH] 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] 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]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH]

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Leukemia: Cancer of blood-forming tissue. [NIH] Leukocyte Count: A count of the number of white blood cells per unit volume in venous blood. A differential leukocyte count measures the relative numbers of the different types of white cells. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] 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] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] 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]

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Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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 Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Liposarcoma: A rare cancer of the fat cells. [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]

Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] 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] Locally advanced cancer: Cancer that has spread only to nearby tissues or lymph nodes. [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] 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

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given risk factor. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH]

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Lymphosarcoma: An obsolete term for a malignant tumor of lymphatic tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [EU]

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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] 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] Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH]

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Mannans: Polysaccharides consisting of mannose units. [NIH] Masseter Muscle: A masticatory muscle whose action is closing the jaws. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the

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endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental 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] 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] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metamorphosis: The ontogeny of insects, i. e. the series of changes undergone from egg, through larva and pupa, or through nymph, to adult. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] 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] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural

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changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell. [NIH] Microvillus: A minute process or protrusion from the free surface of a cell. [EU] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] 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,

272 White Blood Cells

can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of 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] Mucosal Ulceration: Skin ulceration in workers who work with lime and lime solutions. [NIH]

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] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH]

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Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycoplasma Infections: Infections with species of the genus Mycoplasma. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [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] 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] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH]

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Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrectomy: Surgery to remove a kidney. Radical nephrectomy removes the kidney, the adrenal gland, nearby lymph nodes, and other surrounding tissue. Simple nephrectomy removes only the kidney. Partial nephrectomy removes the tumor but not the entire kidney. [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] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [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] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [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] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of

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emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] 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] 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] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It 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.

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[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] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [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] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestradiol: Growth hormone. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in

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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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] 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 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] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] 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] 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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU]

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Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteoradionecrosis: Necrosis of bone following radiation injury. [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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [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 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] 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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [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] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior

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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] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] 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] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial Thromboplastin Time: Test of the intrinsic (factors VIII, IX, XI, and XII) and common (fibrinogen, prothrombin, factors V and X) pathways of coagulation in which a mixture of plasma and phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides) is recalcified and the time required for the appearance of fibrin strands measured. Activation may be provided by contact with the glass tube or exposure to activators (e.g., ellagic acid, particulate silicates such as diatomaceous earth or kaolin) before addition of the calcium chloride. It is used as a screening test and to monitor heparin therapy. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH]

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Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [NIH] 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 vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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

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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] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove 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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] 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] Pheresis: A procedure in which blood is collected, part of the blood such as platelets or white blood cells is taken out, and the rest of the blood is returned to the donor. Also called apheresis. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in

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drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or 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] Phosphorylase a: The phosphorylated and more active form of phosphorylase that functions as a regulatory enzyme during glycogen breakdown. The phosphate groups are hydrolytically removed by phosphorylase phosphatase to form phosphorylase B and orthophosphate. EC 2.4.1.-. [NIH] Phosphorylase Phosphatase: An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 3.1.3.17. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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] Phycoerythrin: The metal-free red phycobilin pigment in a conjugated chromoprotein of red algae. It functions as a light-absorbing substance together with chlorophylls. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH]

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Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasminogen Inactivators: Important modulators of the activity of plasminogen activators. Four inhibitors, all belonging to the serpin family of proteins, have been implicated in plasminogen activation inhibition. They are PAI-1, PAI-2, protease-nexin, and protein C inhibitor (PAI-3). All inhibit both the tissue-type and urokinase-type plasminogen activators. [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]

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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 Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU]

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Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Density: Number of individuals in a population relative to space. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH]

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Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] 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] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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] 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] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] 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] Prostatitis: Inflammation of the prostate. [EU]

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Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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 Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [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] 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]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [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 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] Protozoan Infections: Infections with unicellular organisms of the subkingdom Protozoa. [NIH]

Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a

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predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH]

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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] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original

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form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractometer: Any of several objective or subjective devices for measuring the refractive state of an eye. [NIH] Refractory: Not readily yielding to treatment. [EU] 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] 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]

Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

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 Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] 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

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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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [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 Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticulocytes: Immature erythrocytes. In humans, these are erythroid cells that have just undergone extrusion of their cell nucleus. They still contain some organelles that gradually decrease in number as the cells mature. ribosomes are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the endoplasmic reticulum), hence the name reticulocytes. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [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] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance

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to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [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] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Root Planing: A procedure for smoothing of the roughened root surface or cementum of a tooth after subgingival curettage or scaling, as part of periodontal therapy. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [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] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH]

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Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [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] Screening: Checking for disease when there are no symptoms. [NIH] Scrub Typhus: An acute infectious disease caused by Orientia tsutsugamushi. It is limited to eastern and southeastern Asia, India, northern Australia, and the adjacent islands. Characteristics include the formation of a primary cutaneous lesion at the site of the bite of an infected mite, fever lasting about two weeks, and a maculopapular rash. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a 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] 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] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Self Medication: The self administration of medication not prescribed by a physician or in a manner not directed by a physician. [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]

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Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] 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] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit serine endopeptidases. [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] Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of serine endopeptidases, and some serpins occur in plants where their function is not known. [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] 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]

Shock, Septic: Shock due to circulatory insufficiency caused most commonly by gramnegative bacteremia. It is less often the result of the persistent presence of other microorganisms in the blood (fungemia, viremia); in rare instances, it is caused by gram-positive organisms, but with different symptomatology. [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]

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Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [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] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] 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,

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27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [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] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] 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] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH]

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Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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] 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] 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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [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] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU]

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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] 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] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] 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]

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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH]

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Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] 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] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the

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treatment of Alzheimer's disease and other central nervous system disorders. [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 atomic weight 98.91. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [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] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [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] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [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] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombin Time: Test of the conversion of fibrinogen to fibrin by thrombin in which clotting time of plasma mixed with a thrombin solution is measured. Time is prolonged by afibrinogenemia, abnormal fibrinogen, or the presence of inhibitory substances, e.g., fibrinfibrinogen degradation products, heparin. Batroxobin, a thrombin-like enzyme unaffected

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by the presence of heparin, may be used in place of thrombin. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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]

Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Tonicity: The normal state of muscular tension. [NIH] Tonsil: A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the pharynx situated on each side of the fauces, between the anterior and posterior pillars of the soft palate. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures

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preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1. [NIH]

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] 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] 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] 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 ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein

Dictionary 303

through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [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] Trismus: Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [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] 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 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] 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] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU]

304 White Blood Cells

Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] 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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [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] Unresectable: Unable to be surgically removed. [NIH] 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] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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] 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]

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

Dictionary 305

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] Urocanic Acid: 4-Imidazoleacrylic acid. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [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, 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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [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] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] 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] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] 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]

306 White Blood Cells

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 fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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] Xanthine: An urinary calculus. [NIH]

Dictionary 307

Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [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]

309

INDEX A Abacavir, 29, 213 Abdomen, 213, 226, 241, 244, 253, 262, 266, 280, 296, 297, 300 Abdominal, 4, 12, 68, 148, 171, 176, 213, 239, 250, 270, 279, 280, 281, 290, 304 Abdominal Pain, 4, 148, 171, 176, 213, 250, 281, 304 Ablate, 46, 213, 242 Ablation, 46, 213 Abscess, 4, 213 Acceptor, 213, 266, 278, 302 Acetaldehyde, 22, 64, 213 Acetylcholine, 140, 213, 231, 267, 275 Acetylcholinesterase, 140, 213 Acetylgalactosamine, 213, 252 Acetylglucosamine, 213, 252 Acoustic, 161, 213 Acquired Immunodeficiency Syndrome, 118, 180, 213 Acremonium, 213, 230 Acrylonitrile, 140, 213, 292 Actin, 42, 214, 250 Acute lymphoblastic leukemia, 87, 116, 214 Acute lymphocytic leukemia, 214 Acute myelogenous leukemia, 214 Acute myeloid leukemia, 116, 214 Acute nonlymphocytic leukemia, 214 Acute renal, 23, 214, 255 Adaptability, 214, 229, 230 Adaptation, 20, 214, 283 Adduct, 22, 39, 51, 57, 58, 62, 64, 65, 74, 80, 84, 214 Adenine, 214 Adenocarcinoma, 214, 255 Adenosine, 50, 214, 227, 258, 282 Adenovirus, 158, 214 Adhesives, 213, 214 Adipose Tissue, 214, 266 Adjustment, 214 Adjuvant, 150, 214, 250 Adrenal Cortex, 214, 236, 286, 290 Adrenal Medulla, 215, 228, 244, 276 Adrenergic, 27, 215, 220, 241, 244, 267 Adverse Effect, 215, 232, 294 Aerosol, 35, 215, 298 Affinity, 141, 164, 215, 222, 232, 274, 295

Age Groups, 7, 215 Aged, 80 and Over, 215 Agonist, 50, 215, 241, 275 Air Pollutants, 30, 215 Albumin, 124, 153, 215, 278, 283, 299 Aldehyde Dehydrogenase, 22, 215 Alertness, 215, 226 Algorithms, 215, 224 Alkaline, 6, 66, 215, 217, 227, 233 Alkaloid, 215, 227, 275, 292 Alkylating Agents, 215, 238 Alleles, 25, 140, 216, 265 Allergen, 216, 294 Allo, 14, 32, 216 Allogeneic, 31, 73, 216, 252, 280 Allograft, 79, 85, 216 Allopurinol, 66, 216 Allylamine, 216 Alopecia, 216, 237 Alpha 1-Antichymotrypsin, 216, 294 Alpha 1-Antitrypsin, 216, 294 Alpha Particles, 216, 289 Alpha-1, 125, 216, 282 Alternative medicine, 184, 216 Amebiasis, 216, 270 Amine, 100, 141, 216, 256 Amino Acid Sequence, 216, 218, 246, 250, 294 Amino Acid Substitution, 21, 217, 255 Amino Acids, 42, 49, 216, 217, 218, 228, 245, 250, 275, 280, 284, 287, 294, 298, 302, 304 Amino-terminal, 34, 217 Ammonia, 216, 217, 304 Amnion, 217, 231 Ampicillin, 4, 217 Amplification, 41, 83, 129, 217 Amylase, 5, 217 Anaemia, 217, 269 Anaesthesia, 217, 260 Anal, 122, 217, 248 Analog, 139, 213, 217, 232, 248, 258, 264 Analogous, 217, 302 Analytes, 167, 217 Anaphylactic, 135, 169, 217 Anaphylatoxins, 217, 233 Anaphylaxis, 217

310 White Blood Cells

Anatomical, 178, 218, 222, 240, 243, 259, 293 Anemia, Sickle Cell, 142, 154, 218 Anemic, 14, 218 Anergy, 218, 298 Anesthesia, 218, 268 Aneurysm, 218, 220, 305 Angina, 73, 218 Angiogenesis, 50, 218 Angiotensinogen, 218, 290, 294 Animal model, 14, 21, 32, 33, 35, 218 Anions, 215, 218, 263, 294 Annealing, 218, 284 Anorexia, 218, 250 Antagonism, 218, 227, 232 Anthropometry, 26, 218 Antibacterial, 218, 232, 276 Antibiotic, 7, 9, 11, 136, 177, 217, 218, 226, 245, 249, 265, 280 Antibiotic Prophylaxis, 9, 218 Anticoagulant, 130, 219, 287 Anticonvulsant, 16, 219, 227, 305 Antidepressant, 219, 236 Antifungal, 177, 219, 248 Antigen-Antibody Complex, 219, 233 Antigen-presenting cell, 219, 238 Antihypertensive, 27, 219 Anti-infective, 219, 262 Anti-inflammatory, 28, 43, 50, 219, 236, 251, 279 Anti-Inflammatory Agents, 28, 219, 236 Antimetabolite, 219, 226, 245, 248 Antimicrobial, 7, 9, 151, 178, 219 Antineoplastic, 82, 215, 219, 226, 236, 237, 248, 257, 278, 302 Antioxidant, 48, 76, 83, 149, 219, 221, 226, 278 Antiplasmin, 219, 294 Antipruritic, 219, 232 Antipsychotic, 219, 232, 274 Antiseptic, 220, 228 Antiviral, 8, 220, 226, 261 Anus, 148, 171, 217, 220, 226, 290 Aorta, 220, 228, 290, 306 Aortic Aneurysm, 68, 220 Aperture, 136, 220 Apheresis, 115, 127, 220, 281 Aplasia, 142, 154, 220 Aplastic anemia, 129, 142, 154, 220 Apolipoproteins, 220, 266 Apoptosis, 23, 37, 44, 46, 50, 53, 151, 152, 220

Aqueous, 124, 151, 153, 162, 220, 223, 237, 243 Arachidonate 12-Lipoxygenase, 220, 266 Arachidonate 15-Lipoxygenase, 220, 266 Arachidonate Lipoxygenases, 220, 266 Arachidonic Acid, 220, 221, 258 Arenavirus, 23, 221 Arginine, 217, 221, 275 Aromatic, 30, 51, 55, 56, 57, 64, 65, 70, 75, 80, 84, 85, 165, 221, 228, 281, 297 Arterial, 49, 93, 176, 216, 221, 231, 235, 257, 287, 299, 302 Arteries, 220, 221, 225, 228, 236, 263, 267, 270, 273, 304 Arteriolar, 221, 226, 290 Arterioles, 221, 225, 227 Arteriolosclerosis, 221 Arteriosclerosis, 151, 221 Articular, 89, 221 Asbestos, 59, 77, 100, 221 Asbestosis, 221 Ascites, 221 Ascitic Fluid, 89, 221 Ascorbic Acid, 39, 221, 257 Aseptic, 221, 277, 297 Aspirate, 18, 221 Aspiration, 40, 161, 221 Astringent, 221, 228 Astrocytes, 46, 222, 251, 272, 274 Asymptomatic, 7, 10, 28, 216, 222 Atrium, 222, 228, 235, 306 Attenuated, 168, 222, 240 Atypical, 222, 232, 260 Autoantibodies, 25, 222 Autoantigens, 222 Autoimmune disease, 10, 15, 25, 31, 133, 222, 272 Autoimmunity, 33, 47, 222 Autologous, 127, 222, 280 Autonomic, 213, 220, 222, 276, 298 Autophagocytosis, 133, 222 Autosuggestion, 222, 258 Axonal, 49, 222, 307 Axons, 46, 222, 277, 286 B Bacteremia, 8, 222, 294 Bacterial Adhesion, 92, 222 Bacterial Infections, 95, 222, 230, 265 Bacterial Physiology, 214, 223 Bactericidal, 223, 245 Bacteriophage, 223, 302, 306 Bacteriostatic, 223, 245

Index 311

Bacterium, 16, 151, 223, 224, 233, 234, 255 Bacteriuria, 7, 137, 223, 304 Barbiturate, 223, 300 Base, 18, 22, 39, 51, 64, 71, 162, 214, 223, 238, 239, 250, 264, 300 Basophils, 141, 146, 165, 223, 253, 265 Benign, 3, 6, 10, 67, 145, 221, 223, 253, 274, 289, 306 Benzene, 58, 223 Benzo(a)pyrene, 51, 223 Bewilderment, 223, 234 Bilateral, 223, 291 Bile, 223, 231, 249, 256, 263, 266, 297 Bile Ducts, 223, 231 Bile Pigments, 223, 263 Biliary, 175, 223 Bilirubin, 87, 175, 215, 223, 257 Binding agent, 160, 223 Binding Sites, 38, 160, 224 Bioassay, 224 Biochemical, 18, 38, 45, 54, 55, 62, 72, 81, 87, 152, 216, 219, 224, 248, 264, 294 Biological Assay, 167, 224 Biological response modifier, 224, 261 Biological therapy, 224, 253 Biological Transport, 224, 240 Biomarkers, 18, 30, 56, 57, 71, 74, 84, 224 Biopsy, 5, 18, 118, 224 Biosynthesis, 221, 224, 267, 287, 294, 295, 305 Biotechnology, 22, 53, 164, 170, 184, 197, 224 Bipolar Disorder, 36, 224 Bismuth, 11, 224 Bismuth Subsalicylate, 11, 224 Bladder, 39, 66, 177, 224, 237, 262, 272, 286, 304 Blastocyst, 224, 234, 278, 283, 303 Bleeding Time, 20, 224 Blood Banks, 132, 157, 163, 225 Blood Cell Count, 37, 122, 135, 143, 145, 159, 165, 173, 202, 225, 254, 281 Blood Coagulation, 20, 44, 225, 227, 301 Blood Coagulation Factors, 225 Blood Glucose, 225, 254, 261 Blood Platelets, 42, 149, 186, 225, 269, 284, 294, 301 Blood pressure, 27, 29, 198, 219, 225, 228, 257, 272, 296 Blood transfusion, 124, 153, 162, 225 Blood urea, 5, 175, 185, 225 Blood Volume, 127, 225

Blood-Brain Barrier, 225, 299 Body Burden, 225, 264 Body Composition, 26, 225 Body Fluids, 224, 225, 226, 295, 303 Bone marrow aspiration, 40, 202, 225 Bone Marrow Cells, 225, 233, 269 Bone Marrow Transplantation, 73, 116, 163, 225 Bone scan, 225, 293 Bowel, 65, 105, 107, 148, 171, 176, 217, 226, 240, 260, 262, 264, 281, 297, 304 Bowel Movement, 226, 240, 297 Brachial, 49, 226 Brachytherapy, 226, 262, 263, 289, 307 Bradykinin, 226, 275, 283 Branch, 209, 226, 250, 267, 279, 288, 290, 296, 299, 300 Breakdown, 225, 226, 240, 249, 282, 295 Breath Tests, 48, 226 Breeding, 14, 226 Broad-spectrum, 217, 226, 230, 276 Bromodeoxyuridine, 118, 226 Bronchi, 226, 244, 269, 302 Bronchial, 74, 160, 226, 256 Bronchiectasis, 49, 226 Bronchoalveolar Lavage, 43, 226 Buccal, 18, 19, 226, 267, 297 Butylated Hydroxyanisole, 100, 226 Butylated Hydroxytoluene, 100, 226 Butyric Acid, 226, 245 Bypass, 43, 226 C Caffeine, 48, 75, 226 Calcification, 221, 227 Calcium, 30, 36, 59, 74, 175, 221, 227, 233, 250, 279, 287, 295 Calcium Chloride, 227, 279 Camptothecin, 66, 100, 227 Cancer vaccine, 150, 227 Candidiasis, 227, 248 Capillary, 52, 133, 225, 226, 227, 266, 306 Capsules, 29, 227, 250 Carbamazepine, 16, 227 Carbohydrate, 29, 227, 236, 251, 252, 285 Carbon Dioxide, 227, 238, 248, 249, 283, 291, 305 Carboxy, 227 Carboxylic Acids, 154, 227 Carcinoembryonic Antigen, 21, 228 Carcinogen, 22, 57, 214, 223, 228, 270 Carcinogenesis, 19, 22, 51, 56, 64, 65, 66, 70, 72, 75, 84, 91, 228

312 White Blood Cells

Carcinogenic, 22, 51, 215, 223, 228, 232, 260, 276, 277, 286, 297 Carcinoma, 46, 228 Cardiac, 17, 27, 50, 216, 227, 228, 235, 245, 254, 273, 297 Cardiac arrest, 17, 228 Cardiology, 50, 228 Cardiomyopathy, 50, 228 Cardiopulmonary, 43, 228 Cardiopulmonary Bypass, 44, 228 Cardiovascular, 27, 28, 50, 60, 151, 228, 294 Cardiovascular disease, 28, 151, 228 Cardiovascular Physiology, 50, 228 Cardiovascular System, 228 Carotid Arteries, 17, 228 Carrier Proteins, 228, 283, 289 Carrier State, 55, 216, 228 Case-Control Studies, 26, 228 Catechol, 79, 228 Catecholamine, 58, 228, 241, 281 Catheterization, 229, 262 Catheters, 6, 7, 178, 229, 249, 259, 262 Cations, 229, 263 Caudal, 229, 285 Causal, 229, 262 Cecum, 229, 264 Celiac Disease, 5, 229 Cell Adhesion, 34, 139, 229, 261 Cell Adhesion Molecules, 139, 229 Cell Aggregation, 133, 229 Cell Count, 34, 37, 122, 135, 143, 159, 163, 229 Cell Cycle, 229, 232, 287 Cell Death, 40, 105, 152, 220, 229, 251, 273 Cell Differentiation, 47, 113, 229, 295 Cell Division, 152, 222, 229, 253, 262, 269, 271, 283, 293, 300 Cell Lineage, 47, 229 Cell membrane, 168, 224, 228, 229, 239, 246, 249, 263, 271, 282, 296 Cell motility, 36, 229 Cell proliferation, 81, 221, 229, 262, 295 Cell Size, 229, 248 Cell Survival, 230, 253 Cell Transplantation, 10, 33, 117, 230 Cellobiose, 230 Cellular Structures, 230, 271 Cellulose, 140, 230, 249, 283 Central Nervous System Infections, 180, 230, 253

Centrifugation, 13, 21, 123, 124, 126, 131, 149, 153, 156, 162, 230, 254 Cephalosporins, 4, 230 Cerebellar, 36, 230 Cerebellum, 230 Cerebral, 40, 83, 88, 225, 230, 245, 255, 268, 288, 299, 302 Cerebrospinal, 37, 93, 95, 175, 230 Cerebrospinal fluid, 37, 93, 95, 175, 230 Cerebrovascular, 228, 230 Cerebrum, 230 Cervix, 117, 160, 230 Character, 230, 238, 252 Chemokines, 46, 230 Chemotactic Factors, 231, 233, 275 Chemotherapy, 109, 116, 117, 150, 159, 165, 186, 231 Chimeras, 31, 231 Chlorophyll, 231, 249 Cholangiography, 231, 262 Cholecystography, 231, 262 Cholesterol, 5, 24, 83, 175, 185, 223, 231, 236, 257, 266, 267, 295, 297 Cholesterol Esters, 231, 266 Choline, 213, 231 Cholinergic, 140, 220, 231, 275 Chorioamnionitis, 49, 231 Chorion, 231 Chorioretinitis, 231, 291 Choroid, 231, 291 Chromatin, 70, 97, 152, 220, 231, 296, 300 Chromosomal, 27, 81, 217, 231, 270, 300 Chromosome, 231, 234, 256, 265, 270, 293, 300, 304 Chronic Disease, 130, 231, 264 Chronic renal, 4, 6, 60, 231 Chylomicrons, 231, 266 Cisplatin, 94, 102, 231 Citrus, 221, 232 Claviceps, 232, 292 Clindamycin, 4, 232 Clinical Medicine, 232, 285 Clinical trial, 7, 10, 13, 18, 21, 33, 36, 39, 115, 119, 176, 197, 198, 232, 235, 237, 287, 289 Cloning, 34, 224, 232 Clozapine, 61, 159, 232 Coal, 56, 223, 232 Coal Tar, 56, 232 Coenzyme, 221, 232, 267, 295 Cofactor, 72, 232, 287, 294, 301 Coke, 56, 62, 232

Index 313

Colitis, 108, 148, 171, 232 Collagen, 7, 214, 232, 247, 250, 284, 286 Colloidal, 141, 215, 233, 242, 246, 294, 298 Colony-Stimulating Factors, 233, 253 Colorectal, 21, 107, 233 Combination chemotherapy, 116, 233 Comet Assay, 66, 71, 78, 233 Competency, 150, 233 Complement, 44, 58, 81, 139, 217, 233, 234, 250, 261, 283, 294 Complement 1, 233, 294 Complement 1 Inactivators, 233, 294 Complementary and alternative medicine, 105, 111, 233 Complementary medicine, 105, 234 Complete remission, 234, 290 Compress, 234, 255 Computational Biology, 197, 234 Computed tomography, 12, 118, 234, 293 Computerized axial tomography, 234, 293 Computerized tomography, 234 Conception, 234, 247, 297 Confusion, 198, 234, 240, 275, 304 Congestive heart failure, 50, 234 Conjugated, 141, 144, 155, 234, 282 Conjugation, 51, 134, 234 Conjunctiva, 235, 260 Connective Tissue, 6, 221, 225, 232, 235, 247, 249, 250, 267, 270, 292, 297, 299 Connective Tissue Cells, 235 Consciousness, 235, 238, 241, 244, 296, 299 Constipation, 220, 235, 281 Constitutional, 235, 273, 291 Constriction, 235, 263 Consultation, 10, 235, 246 Consumption, 22, 41, 70, 75, 235, 239, 250, 276, 291 Contamination, 41, 126, 132, 137, 157, 235 Contraindications, ii, 235 Contrast Media, 235, 262 Control group, 49, 235 Convulsion, 224, 235 Coordination, 18, 198, 230, 235, 272 Cor, 235 Coronary, 50, 77, 228, 235, 236, 270, 273 Coronary heart disease, 77, 228, 236 Coronary Thrombosis, 236, 270, 273 Corpus, 236, 280, 286 Corpus Luteum, 236, 286 Cortex, 236, 277 Cortical, 36, 236, 246, 293 Corticosteroid, 8, 236, 285

Cortisol, 96, 215, 236 Cotinine, 30, 236 Coumarins, 236, 287 Cranial, 230, 236, 253, 277 Craniocerebral Trauma, 236, 253 Creatine, 175, 236 Creatinine, 5, 6, 175, 185, 236 Criterion, 7, 236 Cryptococcosis, 236, 237 Cryptococcus, 198, 236, 237 Cryptococcus neoformans, 198, 236, 237 Cultured cells, 38, 237 Curative, 237, 300 Curettage, 237, 292 Cutaneous, 89, 227, 237, 263, 267, 293 Cyanide, 39, 132, 166, 237 Cyanosis, 237, 255 Cyclic, 165, 227, 237, 253, 275, 282, 293 Cyclophosphamide, 8, 109, 237 Cyclosporine, 117, 190, 237 Cyst, 221, 237 Cysteine, 139, 230, 237, 243, 298 Cystine, 150, 237 Cystitis, 177, 237 Cystoscopy, 4, 237 Cytogenetic Analysis, 101, 237 Cytokine, 4, 21, 23, 31, 33, 35, 43, 52, 63, 150, 158, 237, 280, 300 Cytomegalovirus, 64, 72, 86, 163, 237 Cytopenia, 142, 154, 237 Cytoplasm, 220, 223, 229, 237, 238, 244, 253, 299, 300 Cytosine, 238, 248 Cytoskeleton, 42, 52, 238, 261, 271 Cytostatic, 159, 238 Cytotoxic, 8, 23, 60, 63, 141, 145, 167, 216, 238, 259, 289, 295 Cytotoxic chemotherapy, 8, 60, 238 Cytotoxicity, 24, 51, 63, 216, 232, 238 D Dacarbazine, 79, 238 Databases, Bibliographic, 197, 238 De novo, 34, 238 Deamination, 238, 304 Decarboxylation, 238, 256, 305 Decidua, 238, 283 Defense Mechanisms, 4, 238, 261 Defibrillation, 17, 238 Degenerative, 158, 238, 251, 255 Dehydration, 6, 238 Dehydroepiandrosterone, 146, 238 Deletion, 17, 220, 238

314 White Blood Cells

Dementia, 213, 219, 238 Denaturation, 238, 284 Dendrites, 238, 275 Dendritic, 21, 31, 152, 238, 269 Dendritic cell, 21, 31, 152, 238 Density, 21, 26, 52, 122, 126, 149, 160, 164, 230, 239, 248, 266, 277, 284 Dental Care, 186, 239 Dental Caries, 186, 239 Dentists, 177, 239 Deoxyguanosine, 56, 77, 239 Deoxyribonucleic, 56, 64, 85, 239 Deoxyribonucleic acid, 56, 64, 85, 239 Deoxyribonucleotides, 239, 292 Depolarization, 239, 295 Dermal, 56, 239 Deuterium, 239, 257 Developing Countries, 12, 239 Diabetes Mellitus, 28, 239, 251, 254 Diabetic Foot, 94, 239 Diagnostic Imaging, 176, 239 Diagnostic procedure, 121, 132, 184, 239, 282 Dialyzer, 239, 254 Diapedesis, 52, 239 Diaphragm, 239, 284 Diarrhea, 11, 79, 148, 171, 176, 216, 224, 240, 260 Diarrhoea, 240, 250 Diastolic, 240, 257 Dietary Fats, 240, 265 Diffusion, 175, 224, 240, 253, 260, 304 Digestion, 222, 223, 226, 240, 260, 262, 265, 266, 297, 305 Digestive system, 119, 240, 272 Digestive tract, 240, 295 Dilatation, 218, 226, 240, 262, 286, 305 Dilatation, Pathologic, 240, 305 Dilation, 226, 240, 305 Dilution, 123, 128, 145, 146, 240, 245, 283 Dimerization, 72, 240 Dimethyl, 154, 240, 267 Direct, iii, 9, 141, 161, 168, 177, 189, 232, 240, 241, 251, 290, 299 Disease Progression, 25, 31, 33, 240 Disinfectant, 240, 245 Disorientation, 234, 240 Disposition, 21, 240 Dissection, 47, 240 Dissociation, 38, 215, 240, 263 Dissociative Disorders, 240, 241 Distal, 222, 241, 286

Diuresis, 227, 241 Dizziness, 148, 241 Domesticated, 241, 253 Dopamine, 220, 232, 241, 272, 281 Dorsal, 47, 241, 285 Dorsum, 241 Dosimeter, 30, 241 Dosimetry, 64, 241 Drive, ii, vi, 5, 11, 44, 99, 167, 174, 175, 177, 241 Drug Interactions, 191, 241 Drug Tolerance, 241, 301 Duodenum, 223, 241, 297 Dura mater, 241, 269, 278 Dyes, 122, 144, 223, 241, 248 Dysentery, 11, 216, 241 Dysgenesis, 36, 242 Dysplasia, 30, 242 Dysuria, 9, 10, 242 E Echocardiography, 50, 242 Edema, 8, 233, 242, 255, 274 Effector, 213, 233, 242, 274, 275, 282 Effector cell, 242, 274, 275 Efficacy, 15, 16, 18, 21, 43, 46, 50, 133, 140, 150, 151, 242 Ejaculation, 4, 242, 293 Elasticity, 221, 242 Elastin, 232, 242 Elective, 89, 242 Electric shock, 238, 242 Electrocardiogram, 118, 242 Electrocoagulation, 232, 242 Electrolyte, 11, 236, 242, 254, 285, 296 Electrons, 219, 223, 242, 262, 263, 278, 289 Electrophoresis, 19, 45, 66, 90, 233, 242, 263 Electroplating, 228, 242 Ellagic Acid, 242, 279 Emaciation, 213, 242 Embryo, 217, 224, 229, 242, 260, 270, 304 Empiric, 9, 11, 12, 243 Empirical, 175, 243 Emulsion, 243, 248 Enamel, 239, 243 Encapsulated, 243, 266 Encephalitis, 243 Encephalomyelitis, 25, 243 Endemic, 243, 268 Endocrine System, 243, 274 Endometrium, 238, 243, 270, 303 Endopeptidases, 243, 287, 294

Index 315

Endothelial cell, 20, 23, 34, 44, 52, 139, 225, 243, 301 Endothelium, 20, 52, 148, 170, 239, 243, 275, 283 Endothelium, Lymphatic, 243 Endothelium, Vascular, 243 Endothelium-derived, 243, 275 Endotoxic, 244, 265 Endotoxin, 52, 244, 303 End-stage renal, 231, 244 Enhancer, 50, 244 Environmental Health, 56, 59, 67, 74, 85, 196, 198, 244 Environmental Pollutants, 51, 244 Environmental tobacco smoke, 30, 244 Enzymatic, 227, 233, 239, 244, 247, 256, 284 Enzyme Inhibitors, 244, 283 Eosinophil, 141, 244 Eosinophilia, 175, 244 Eosinophilic, 175, 244 Eosinophilic Gastroenteritis, 175, 244 Epidemiological, 186, 244 Epidermal, 139, 244, 269, 306 Epidermal Growth Factor, 139, 244 Epidermis, 244, 288 Epigastric, 244, 279 Epilepticus, 40, 244 Epinephrine, 215, 241, 244, 276, 303 Epithelial, 31, 57, 160, 214, 224, 238, 244, 245, 255 Epithelial Cells, 57, 244, 245, 255 Epithelium, 8, 30, 74, 243, 245, 279 Epitope, 25, 245 Epoprostenol, 245, 258 Ergot, 245, 292 Erythroblasts, 90, 143, 154, 245 Erythrocyte Indices, 225, 245 Erythrocyte Volume, 225, 245 Erythrocytes, 75, 131, 157, 217, 218, 225, 245, 255, 290, 291, 294 Erythroid Progenitor Cells, 245 Erythromycin, 4, 245 Erythropoiesis, 245 Escalation, 43, 245 Esophagus, 148, 171, 240, 245, 254, 269, 281, 297 Estrogen, 9, 26, 245 Ethanol, 22, 151, 245 Ethionine, 245 Ethnic Groups, 26, 246 Eukaryotic Cells, 246, 259, 277 Evacuation, 235, 246, 264, 288

Excitation, 144, 246, 248 Excitatory, 246, 252 Exhaustion, 218, 246, 268 Exocrine, 246, 278 Exocytosis, 139, 246, 299 Exogenous, 21, 168, 246, 294 Exon, 55, 246 Expert Systems, 246, 258 Extender, 148, 246 Extensor, 246, 288 External-beam radiation, 246, 263, 289, 307 Extracellular, 30, 38, 44, 222, 235, 246, 247, 261, 274, 295 Extracellular Matrix, 235, 246, 247, 261 Extracorporeal, 44, 69, 152, 190, 246, 254 Extracorporeal Circulation, 44, 246 Extraction, 19, 129, 168, 246 Eye Infections, 214, 246 F Family Planning, 197, 246 Fat, 11, 24, 214, 221, 225, 226, 235, 236, 246, 265, 266, 272, 285, 292, 296, 298, 299, 301, 303 Fatigue, 140, 176, 198, 246, 254 Fatty acids, 55, 215, 228, 247, 252, 266 Febrile, 11, 127, 247, 268 Fecal occult blood test, 11, 247 Feces, 11, 228, 235, 247, 297 Femoral, 49, 228, 247 Femoral Artery, 228, 247 Femur, 247 Ferritin, 60, 85, 247 Fetal Blood, 231, 247 Fetal Hemoglobin, 14, 142, 154, 247 Fetus, 14, 231, 247, 283, 304, 305 Fibrillation, 238, 247 Fibrin, 19, 219, 225, 247, 279, 281, 283, 300, 301 Fibrinogen, 19, 29, 84, 247, 279, 283, 287, 300 Fibrinolysis, 19, 20, 44, 247 Fibrinolytic, 19, 20, 74, 233, 247 Fibroblasts, 55, 57, 75, 235, 247, 261 Fibronectin, 170, 247 Fibrosis, 43, 71, 216, 247, 292, 293 Filtration, 75, 88, 162, 247 Fixation, 44, 247, 294 Fixatives, 132, 248 Flank Pain, 10, 248 Flatus, 248, 249

316 White Blood Cells

Flow Cytometry, 14, 52, 63, 123, 132, 141, 143, 144, 145, 146, 147, 248, 259 Fluconazole, 198, 248 Flucytosine, 198, 248 Fluorescence, 38, 72, 75, 81, 122, 134, 138, 144, 248 Fluorescent Dyes, 127, 134, 248 Fluorouracil, 109, 248, 265 Folate, 248, 249 Fold, 17, 39, 40, 52, 248 Folic Acid, 143, 154, 248 Follicles, 249 Foot Ulcer, 239, 249 Foramen, 249, 280 Forearm, 225, 249 Fovea, 248, 249 Fractionation, 124, 140, 153, 164, 249 Fungemia, 249, 294 Fungi, 177, 219, 232, 234, 246, 249, 253, 270, 271, 307 Fungus, 151, 176, 198, 227, 230, 236, 237, 245, 249, 292 G Galactosidases, 61, 249 Gallbladder, 213, 223, 231, 240, 249 Gallium, 79, 249 Gamma Rays, 249, 272, 289 Ganglia, 213, 220, 249, 274, 298 Gap Junctions, 249, 299 Gas, 21, 217, 227, 240, 248, 249, 257, 260, 272, 275, 276, 298, 305 Gas exchange, 249, 305 Gasoline, 223, 250 Gastric, 244, 250, 254, 256 Gastrin, 250, 256 Gastroenteritis, 175, 250 Gastrointestinal, 8, 148, 152, 171, 175, 221, 226, 228, 244, 245, 250, 268, 294, 298, 303 Gastrointestinal Neoplasms, 221, 250 Gastrointestinal tract, 148, 152, 171, 175, 228, 245, 250, 294, 303 Gelatin, 140, 250, 298 Gelsolin, 42, 250 Gemcitabine, 76, 250 Gene Expression, 16, 23, 28, 33, 39, 45, 46, 82, 93, 101, 250 General practitioner, 177, 250 Genetic Code, 250, 276 Genetic Engineering, 224, 232, 250 Genetic Predisposition to Disease, 27, 250 Genetic testing, 250, 284 Genetics, 19, 47, 234, 250, 271

Genital, 250, 305 Genitourinary, 10, 12, 250, 305 Genitourinary system, 12, 250 Genotype, 28, 251, 281 Germ Cells, 251, 269, 278, 296 Gestation, 18, 32, 251, 280, 283 Giant Cells, 251, 292 Giardiasis, 251, 270 Gland, 38, 118, 214, 215, 236, 251, 267, 274, 278, 279, 286, 293, 297, 298, 301 Gliosis, 36, 251 Glomerular, 6, 45, 251, 290 Glomeruli, 251, 288 Glomerulonephritis, 6, 10, 45, 251 Glomerulus, 251, 274 Glucocorticoid, 251, 285 Gluconeogenesis, 251 Glucose, 5, 29, 105, 175, 185, 221, 225, 230, 239, 251, 252, 254, 261, 282, 292, 304 Glucose Intolerance, 239, 251 Glucose tolerance, 175, 251 Glucose Tolerance Test, 175, 251 Glucosidases, 55, 252 Glutamate, 252 Glutamic Acid, 10, 248, 252, 255, 286 Gluten, 5, 229, 252 Glycerol, 226, 252, 282 Glycerophospholipids, 252, 282 Glycogen, 252, 282 Glycols, 252, 257 Glycoprotein, 52, 72, 176, 216, 219, 228, 233, 247, 251, 252, 253, 272, 301, 303 Glycosaminoglycans, 20, 252 Glycosidic, 230, 252, 282 Gonadal, 252, 297 Governing Board, 252, 285 Grade, 12, 13, 30, 252 Graft, 59, 94, 131, 157, 163, 252, 256, 259, 273 Graft Rejection, 252, 259 Grafting, 162, 252 Graft-versus-host disease, 163, 252, 273 Gram-negative, 8, 244, 252, 273, 276, 294 Gram-positive, 8, 252, 276, 294, 297 Gram-Positive Cocci, 8, 253 Granule, 44, 139, 253 Granulocyte Colony-Stimulating Factor, 49, 155, 233, 253 Granulocytes, 18, 47, 80, 126, 141, 149, 233, 253, 264, 273, 295, 306 Granuloma, 35, 185, 253 Grasses, 232, 249, 253

Index 317

Gravis, 133, 253 Groin, 10, 253 Growth factors, 18, 46, 165, 253 Guanylate Cyclase, 253, 275 Guinea Pigs, 35, 253 H Haematology, 60, 69, 70, 74, 85, 88, 90, 253 Haemodialysis, 82, 96, 253 Hair follicles, 72, 253 Half-Life, 135, 155, 169, 253, 258 Haptens, 215, 253, 289 Headache, 198, 227, 253, 260 Headache Disorders, 253 Heart attack, 228, 254 Heart failure, 254 Heart Transplantation, 43, 254 Heartbeat, 254, 306 Heartburn, 224, 254, 260 Helminthiasis, 230, 254 Hematocrit, 5, 122, 130, 133, 142, 154, 185, 225, 245, 254 Hematogenous, 35, 254 Hematologic malignancies, 33, 254 Hematoma, 254, 255 Hematopoiesis, 142, 154, 254 Hematopoietic Stem Cells, 33, 163, 254 Hematuria, 4, 6, 10, 254 Heme, 143, 154, 223, 254, 255, 285, 305 Hemiparesis, 12, 254 Hemodiafiltration, 254, 304 Hemodialysis, 4, 174, 239, 254, 304 Hemofiltration, 254, 304 Hemoglobin A, 134, 169, 255 Hemoglobin C, 123, 130, 132, 142, 154, 166, 218, 245, 247, 255 Hemoglobin E, 134, 142, 154, 169, 255 Hemoglobin H, 247, 255 Hemoglobin M, 122, 166, 237, 255 Hemolytic, 14, 23, 142, 154, 218, 255, 300 Hemorrhage, 135, 169, 236, 242, 253, 255, 288, 297 Hemorrhagic stroke, 39, 255 Hemostasis, 20, 29, 255, 261, 294 Heparin, 255, 279, 294, 300 Hepatic, 24, 151, 215, 251, 255, 285, 295 Hepatitis, 48, 71, 135, 143, 155, 169, 177, 255, 260 Hepatocellular, 46, 255 Hepatocellular carcinoma, 46, 255 Hepatocytes, 255 Hepatoma, 71, 255 Hepatomegaly, 255, 260

Hereditary, 216, 233, 256, 281, 300 Heredity, 250, 256 Heritability, 49, 256 Herpes, 8, 180, 256 Herpes Zoster, 256 Heterochromatin, 63, 256 Heterodimer, 38, 256 Heterogeneity, 49, 215, 256 Heterotrophic, 249, 256 Histamine, 60, 217, 220, 256, 267 Histidine, 256 Histology, 256, 279 Homologous, 69, 100, 216, 256, 293, 294, 299 Hormonal, 38, 224, 236, 256 Hormone, 38, 75, 185, 216, 224, 236, 244, 250, 256, 261, 262, 269, 276, 286, 292, 293, 295, 301 Host, 4, 5, 9, 33, 35, 41, 125, 131, 157, 180, 223, 228, 256, 258, 259, 292, 305, 306 Human Development, 42, 196, 256 Human papillomavirus, 30, 117, 256 Humoral, 35, 37, 126, 150, 252, 256 Humour, 256 Hybrid, 256, 257, 292 Hybridization, 256, 271 Hybridomas, 257, 261 Hydration, 12, 257 Hydrogen, 17, 213, 216, 223, 227, 238, 239, 257, 266, 271, 275, 276, 278, 287, 307 Hydrogen Bonding, 257, 276 Hydrolases, 243, 249, 257 Hydrolysis, 93, 213, 230, 231, 257, 282, 284, 287 Hydrophilic, 141, 257 Hydrophobic, 252, 257, 266 Hydroxides, 257 Hydroxyl Radical, 42, 257 Hydroxylysine, 233, 257 Hydroxyproline, 233, 257 Hydroxyurea, 79, 257 Hyperbilirubinemia, 257, 263 Hypercholesterolemia, 24, 257 Hyperlipidemia, 24, 257 Hyperlipoproteinemia, 257, 266 Hypersensitivity, 35, 216, 217, 244, 257, 292, 294 Hypersplenism, 142, 154, 257 Hypertension, 4, 12, 27, 48, 90, 221, 228, 235, 245, 253, 257, 258, 274 Hypertension, Renal, 27, 258 Hypertension, Renovascular, 258

318 White Blood Cells

Hypertrophy, 27, 46, 235, 258 Hypnotic, 223, 258, 300 Hypoglycemia, 16, 39, 258 Hypoxanthine, 79, 258, 307 Hypoxia, 16, 39, 135, 169, 218, 258 I Iatrogenic, 3, 258 Id, 102, 106, 203, 208, 210, 258 Idiopathic, 258, 292 Ileitis, 148, 171, 258 Ileum, 229, 258, 306 Iloprost, 94, 258 Image Cytometry, 86, 258 Immune function, 4, 8, 33, 258, 259 Immune Sera, 258 Immunity, 31, 125, 213, 258, 259, 302 Immunization, 14, 32, 91, 94, 168, 258, 259, 294 Immunoassay, 60, 81, 85, 259 Immunocompromised, 72, 259 Immunodeficiency, 134, 179, 180, 198, 202, 213, 259 Immunodeficiency syndrome, 179, 180, 198, 259 Immunogen, 168, 259 Immunogenic, 21, 133, 150, 162, 259, 265, 289 Immunoglobulin, 34, 93, 218, 259, 272 Immunohistochemistry, 50, 259 Immunologic, 14, 21, 44, 140, 161, 164, 216, 231, 258, 259, 280, 289, 301 Immunology, 47, 63, 64, 73, 77, 93, 170, 214, 215, 248, 259 Immunophenotyping, 132, 167, 259 Immunosuppressive, 10, 26, 35, 44, 60, 117, 118, 175, 237, 251, 259 Immunosuppressive Agents, 10, 35, 175, 259 Immunosuppressive therapy, 118, 259 Immunotherapy, 21, 63, 69, 224, 259 Impairment, 223, 246, 259, 270 Implant radiation, 259, 262, 263, 289, 307 In situ, 101, 122, 160, 259 In Situ Hybridization, 101, 259 Incision, 259, 262 Indicative, 173, 260, 279, 305 Indigestion, 224, 260 Induction, 8, 23, 71, 74, 219, 260, 295 Infant, Newborn, 215, 260 Infarction, 255, 260, 291 Infectious Diarrhea, 11, 260 Infectious Mononucleosis, 69, 260

Infertility, 4, 148, 260 Infiltration, 36, 46, 251, 260 Inflammatory bowel disease, 65, 83, 86, 147, 148, 170, 171, 176, 260 Influenza, 31, 260 Infusion, 15, 116, 117, 118, 260, 302 Ingestion, 24, 231, 251, 260, 284 Inhalation, 22, 215, 221, 260, 284 Initiation, 16, 18, 260 Initiator, 125, 224, 260 Inorganic, 231, 257, 260, 272, 282 Insight, 32, 45, 49, 261 Insomnia, 140, 261 Insulator, 261, 272 Insulin, 10, 27, 28, 40, 224, 251, 261, 263, 286 Insulin-dependent diabetes mellitus, 261 Integrins, 44, 261 Intensive Care, 18, 261 Intensive Care Units, 18, 261 Interferon, 48, 57, 81, 100, 110, 125, 261, 267 Interferon-alpha, 261 Interleukin-1, 75, 158, 261 Interleukin-2, 60, 116, 261 Interleukin-6, 12, 94, 261 Interleukins, 259, 261 Intermittent, 162, 262, 267, 280 Internal Medicine, 6, 7, 23, 41, 45, 50, 82, 254, 262, 274 Internal radiation, 262, 263, 289, 307 Interphase, 63, 256, 262 Interstitial, 49, 50, 226, 262, 263, 274, 290, 307 Intervention Studies, 83, 262 Intestinal, 5, 8, 148, 171, 176, 229, 251, 262, 268 Intestine, 148, 171, 226, 262, 264, 297 Intracellular, 30, 31, 38, 45, 75, 152, 227, 260, 261, 262, 269, 275, 285, 289, 293, 295 Intracranial Aneurysm, 27, 262 Intramuscular, 129, 262 Intravascular, 142, 154, 262 Intravenous, 9, 12, 93, 198, 249, 260, 262 Intravenous pyelography, 9, 262 Intrinsic, 52, 135, 142, 144, 154, 215, 262, 279 Intubation, 18, 229, 262 Invasive, 4, 14, 130, 148, 258, 262, 268 Involuntary, 235, 244, 247, 262, 273 Iodine, 175, 262 Iodipamide, 88, 262

Index 319

Ion Channels, 222, 262, 274, 275, 299 Ionization, 262, 263 Ionizing, 64, 65, 87, 216, 241, 263, 268, 289 Ions, 67, 223, 233, 240, 242, 250, 257, 263, 287, 296 Irradiation, 67, 100, 131, 157, 162, 186, 263, 307 Irritants, 242, 263 Ischemia, 17, 40, 50, 255, 263, 291 Ischemic stroke, 39, 263 Islet, 10, 263 Isoelectric, 81, 263 Isoelectric Focusing, 81, 263 Isoelectric Point, 263 Isotonic, 166, 263, 271 Isozymes, 54, 263 J Jaundice, 87, 257, 263 Joint, 12, 15, 65, 67, 129, 158, 176, 221, 263, 298, 299 K Kb, 196, 264 Keratolytic, 239, 264 Keto, 165, 264, 302 Kidney Disease, 5, 27, 39, 119, 177, 196, 264 Kidney stone, 264, 304 Kinetic, 51, 263, 264 L Labile, 233, 264 Lamivudine, 29, 264 Large Intestine, 148, 171, 229, 240, 244, 262, 264, 290, 295 Latency, 35, 264 Latent, 8, 35, 250, 264, 285 Laxative, 11, 264 Lead Poisoning, 142, 154, 264 Least-Squares Analysis, 264, 290 Lectin, 139, 150, 264, 269 Lesion, 33, 46, 249, 251, 253, 264, 266, 293, 303 Lethal, 17, 30, 223, 237, 264 Leucocyte, 140, 216, 244, 264, 267 Leukaemia, 91, 264 Leukapheresis, 220, 264 Leukemia, 33, 47, 107, 116, 117, 174, 247, 254, 265 Leukocyte Count, 6, 135, 173, 265 Leukocytosis, 4, 265 Leukopenia, 67, 148, 155, 174, 265 Levamisole, 8, 265 Levofloxacin, 7, 265

Library Services, 208, 265 Life cycle, 249, 265 Ligament, 265, 286 Ligands, 144, 229, 261, 265 Likelihood Functions, 265, 290 Limbic, 36, 265 Lincomycin, 232, 265 Linear Models, 265, 290 Linkage, 27, 28, 29, 230, 249, 265 Linkage Disequilibrium, 27, 265 Lipase, 5, 24, 265 Lipid, 29, 33, 77, 82, 220, 221, 231, 252, 261, 264, 265, 266, 272, 278, 303 Lipid A, 82, 265 Lipid Peroxidation, 266, 278 Lipopolysaccharide, 252, 266 Lipoprotein, 19, 24, 27, 28, 149, 252, 266, 267 Lipoprotein Lipase, 24, 27, 266 Liposarcoma, 12, 266 Liposomal, 168, 266 Liposomes, 87, 89, 168, 266 Lipoxygenase, 33, 220, 266 Litter, 14, 266 Liver Neoplasms, 246, 266 Liver scan, 266, 293 Localization, 46, 78, 101, 129, 259, 266 Localized, 16, 239, 243, 248, 254, 260, 266, 277, 283, 300, 303 Locally advanced cancer, 117, 266 Locomotion, 36, 78, 266, 283 Logistic Models, 266, 290 Long-Term Care, 50, 267 Loperamide, 11, 267 Lovastatin, 267, 295 Low-density lipoprotein, 28, 89, 93, 266, 267 Lumbar, 15, 267 Lupus, 39, 267, 299 Lymph, 118, 202, 243, 256, 260, 266, 267, 269, 274, 292, 298 Lymph node, 118, 202, 266, 267, 269, 274, 292 Lymphadenopathy, 260, 267 Lymphatic, 243, 260, 267, 268, 270, 296, 301 Lymphatic system, 267, 296, 301 Lymphoblastic, 116, 267 Lymphoblasts, 214, 267 Lymphocyte, 26, 29, 43, 48, 128, 138, 170, 213, 219, 267, 269 Lymphocyte Count, 29, 213, 267

320 White Blood Cells

Lymphocytic, 8, 116, 267 Lymphoid, 116, 129, 218, 264, 267, 301 Lymphoma, 107, 116, 117, 254, 267 Lymphoproliferative, 117, 118, 267 Lymphosarcoma, 168, 268 Lysine, 155, 255, 257, 268 Lytic, 145, 166, 268, 294, 306 M Macrophage, 4, 30, 63, 165, 233, 261, 268 Maculopapular, 268, 293 Magnetic Resonance Imaging, 268, 293 Maintenance therapy, 198, 268 Malabsorption, 5, 229, 268 Malaise, 176, 268 Malaria, 58, 60, 69, 143, 155, 268 Malaria, Falciparum, 268 Malaria, Vivax, 268 Malignancy, 8, 15, 46, 160, 168, 186, 268, 279 Malignant, 75, 79, 80, 94, 95, 168, 213, 214, 219, 221, 258, 268, 272, 274, 289, 292 Malignant Hyperthermia, 75, 268 Malignant tumor, 268, 272 Malnutrition, 215, 268 Mammary, 266, 268 Manic, 219, 224, 268 Manifest, 36, 222, 268 Man-made, 228, 268 Mannans, 249, 269 Masseter Muscle, 269, 303 Meat, 70, 240, 269 Medial, 221, 269 Mediastinum, 269, 301 Mediate, 31, 34, 38, 42, 47, 229, 241, 269 Mediator, 15, 58, 261, 269, 294 Medical Records, 140, 269 MEDLINE, 197, 269 Megakaryocytes, 139, 225, 269 Megaloblastic, 143, 154, 249, 269 Meiosis, 269, 270, 299, 304 Melanin, 269, 281, 303 Melanocytes, 269 Melanoma, 79, 168, 269 Membrane Proteins, 266, 269 Memory, 198, 218, 238, 269 Meninges, 198, 230, 236, 241, 269 Meningitis, 198, 248, 269 Menopause, 269, 285 Menstrual Cycle, 269, 286 Menstruation, 9, 238, 269, 270 Mental Disorders, 120, 270, 288

Mental Health, iv, 13, 120, 196, 199, 270, 288 Mental Processes, 240, 270, 288 Mercury, 248, 270 Mesenchymal, 244, 270 Mesentery, 270, 281 Mesoderm, 270, 303 Metabolite, 22, 30, 39, 51, 240, 267, 270 Metamorphosis, 222, 270 Metastasis, 229, 270 Metastatic, 43, 117, 270 Methionine, 79, 240, 245, 270, 298 Metronidazole, 4, 270 MI, 8, 211, 270 Microbe, 270, 302 Microbiological, 7, 134, 270 Microbiology, 34, 47, 214, 222, 223, 270 Micronuclei, 55, 71, 270 Microorganism, 151, 232, 271, 279, 306 Micro-organism, 239, 271, 294 Microscopy, 36, 52, 68, 161, 271 Microspheres, 50, 271 Microtubules, 271, 278 Microvilli, 52, 271 Microvillus, 52, 271 Midaxillary line, 271, 306 Migration, 34, 49, 271, 274 Millimeter, 271, 306 Mitochondria, 271, 277 Mitochondrial Swelling, 271, 273 Mitosis, 220, 270, 271 Mobility, 158, 181, 271 Modeling, 51, 271 Modification, 141, 152, 250, 271, 288, 307 Modulator, 150, 271 Molecular, 18, 19, 21, 30, 34, 35, 36, 38, 44, 47, 51, 52, 56, 59, 65, 76, 77, 78, 80, 84, 95, 100, 101, 105, 125, 129, 140, 161, 185, 197, 200, 219, 224, 234, 246, 247, 252, 254, 255, 266, 271, 283, 289, 292, 298, 303 Molecular Probes, 38, 271 Monitor, 5, 12, 18, 23, 78, 159, 185, 228, 236, 272, 276, 279 Monoamine, 36, 272 Monoclonal, 15, 31, 44, 63, 89, 134, 145, 257, 263, 272, 289, 307 Monoclonal antibodies, 31, 63, 145, 272 Monocyte, 4, 14, 33, 139, 272 Monotherapy, 16, 178, 272 Morphogenesis, 49, 272 Morphological, 6, 62, 72, 77, 152, 160, 242, 249, 269, 272

Index 321

Morphology, 20, 129, 132, 143, 167, 173, 254, 272 Motility, 36, 149, 250, 272, 294 Motion Sickness, 272, 273 Mucins, 272, 292 Mucolytic, 226, 272 Mucosa, 8, 71, 82, 161, 229, 267, 272, 273, 297 Mucosal Ulceration, 174, 272 Mucositis, 272, 301 Mucus, 6, 242, 272, 304 Multidose, 92, 272 Multiple Myeloma, 6, 272 Multiple sclerosis, 25, 54, 73, 77, 101, 272 Mutagen, 223, 272 Mutagenesis, 51, 56, 65, 84, 90, 273 Mutagenic, 215, 273, 276 Mutagenicity, 22, 273 Myalgia, 260, 273 Myasthenia, 133, 273 Mycophenolate mofetil, 43, 117, 273 Mycoplasma, 230, 273 Mycoplasma Infections, 230, 273 Myelin, 25, 54, 272, 273, 274 Myeloid Cells, 142, 154, 273 Myeloma, 33, 174, 273 Myocardial infarction, 55, 59, 151, 236, 270, 273 Myocarditis, 62, 273 Myocardium, 50, 270, 273 N Narcotic, 213, 273 Nasal Cavity, 273 Nasal Mucosa, 66, 260, 273 Nausea, 148, 198, 220, 224, 250, 260, 273, 304 NCI, 1, 19, 116, 117, 119, 195, 273 Necrosis, 23, 94, 152, 220, 260, 270, 273, 278, 291, 292 Need, 3, 9, 14, 21, 22, 25, 37, 122, 133, 135, 136, 148, 159, 166, 169, 174, 179, 185, 198, 204, 231, 252, 273, 301, 303 Neonatal, 14, 18, 36, 87, 95, 273 Neoplasia, 142, 273, 274 Neoplasm, 117, 274, 292, 303 Neoplastic, 30, 257, 267, 274, 303 Nephrectomy, 12, 274 Nephritis, 45, 274 Nephrologist, 6, 10, 274 Nephrology, 4, 8, 23, 58, 96, 177, 274 Nephropathy, 10, 27, 264, 274 Nephrosis, 274

Nephrotic, 8, 274 Nephrotic Syndrome, 8, 274 Nerve, 46, 47, 55, 140, 215, 218, 222, 238, 269, 272, 274, 277, 279, 285, 291, 293, 297, 303 Nerve Endings, 47, 274 Nervous System, 23, 47, 140, 213, 223, 226, 230, 232, 249, 252, 267, 269, 272, 274, 275, 277, 286, 294, 298, 299, 300 Networks, 45, 258, 274, 300 Neural, 33, 47, 256, 258, 274, 296 Neuroeffector Junction, 274 Neuroendocrine, 37, 274 Neuroglia, 251, 274 Neuroleptic, 219, 232, 274 Neurologic, 17, 37, 275, 302 Neuromuscular, 213, 275, 291 Neuromuscular Junction, 213, 275, 291 Neuronal, 39, 49, 274, 275 Neurons, 46, 140, 238, 246, 249, 274, 275, 298, 299 Neuropeptide, 47, 275 Neuroretinitis, 275, 291 Neurosurgery, 85, 275 Neurotoxicity, 79, 275 Neurotransmitters, 38, 275, 286 Neutrons, 216, 263, 275, 289 Neutropenia, 32, 142, 154, 155, 202, 249, 275 Neutrophil, 4, 5, 36, 44, 52, 136, 141, 202, 216, 275 Neutrophil Activation, 44, 275 Nicotine, 30, 275 Nitric Oxide, 18, 275 Nitrogen, 5, 18, 42, 63, 76, 141, 165, 175, 185, 215, 216, 237, 248, 276, 303 Nitrosamines, 22, 276 Norepinephrine, 215, 241, 276 Nosocomial, 6, 276 Nuclei, 37, 63, 138, 216, 234, 242, 250, 268, 270, 271, 275, 276, 277, 287, 300 Nucleic acid, 37, 41, 128, 129, 138, 145, 162, 170, 238, 250, 256, 258, 259, 276, 286, 307 Nucleic Acid Hybridization, 128, 256, 276 Nutritional Status, 11, 276 O Occult, 247, 276 Occult Blood, 276 Occupational Exposure, 80, 276 Odour, 221, 276 Oestradiol, 146, 276

322 White Blood Cells

Office Visits, 7, 37, 276 Ofloxacin, 7, 276 Ointments, 276, 279 Oligo, 81, 276 Oncogenic, 261, 277, 287 Opacity, 166, 239, 277 Operon, 16, 277, 291 Ophthalmology, 248, 277 Opportunistic Infections, 180, 198, 202, 213, 277 Optic Nerve, 275, 277, 278, 291 Oral Health, 174, 186, 277 Organ Culture, 277, 301 Organ Transplantation, 61, 117, 118, 277 Organelles, 152, 160, 230, 237, 269, 277, 283, 291 Orgasm, 242, 277 Osmolality, 175, 277 Osmoles, 277 Osmosis, 277 Osmotic, 12, 135, 169, 215, 271, 277, 294 Osteoclasts, 222, 277 Osteomyelitis, 64, 176, 277 Osteoporosis, 26, 108, 278 Osteoradionecrosis, 186, 278 Outpatient, 7, 9, 278 Ovalbumin, 278, 294 Ovary, 236, 278, 297 Ovum, 236, 238, 251, 265, 278, 286, 303, 307 Ovum Implantation, 278, 303 Oxidants, 41, 278 Oxidation, 34, 55, 76, 134, 169, 213, 219, 220, 237, 255, 266, 278 Oxidation-Reduction, 278 Oxidative Stress, 42, 278 Oxygenation, 255, 278 Oxygenator, 92, 228, 278 P Pachymeningitis, 269, 278 Paclitaxel, 94, 110, 278 Palate, 278, 297, 301 Palliative, 278, 300 Pancreas, 10, 175, 213, 224, 240, 261, 263, 265, 278, 279, 286, 303 Pancreatic, 10, 279 Papillomavirus, 279 Paraffin, 20, 279 Paralysis, 25, 254, 279 Parasite, 11, 151, 279, 303 Parasitic, 115, 232, 242, 254, 279 Parietal, 279, 280, 284

Parotid, 279, 292 Partial remission, 279, 290 Partial Thromboplastin Time, 20, 279 Particle, 122, 123, 141, 147, 160, 161, 164, 268, 279, 302 Parturition, 60, 279 Pathogen, 9, 11, 16, 23, 47, 168, 279 Pathogenesis, 9, 18, 30, 36, 45, 50, 175, 279 Pathologic, 218, 220, 224, 236, 248, 257, 279, 288 Pathologic Processes, 220, 279 Pathologies, 132, 279 Pathophysiology, 11, 50, 174, 175, 176, 279 Patient Education, 202, 206, 208, 211, 279 Pedigree, 29, 279 Pelvic, 280, 286 Penicillin, 217, 218, 280 Penis, 242, 280, 281 Pentoxifylline, 94, 96, 280 Peptide, 21, 29, 47, 243, 257, 280, 284, 287, 298 Perforation, 220, 249, 280 Performance status, 150, 151, 280 Perfusion, 50, 92, 258, 280 Pericardium, 280, 299 Perinatal, 36, 86, 93, 97, 280 Periodontal disease, 7, 280 Periodontitis, 7, 16, 186, 280 Peripheral blood, 20, 21, 23, 25, 30, 34, 40, 45, 48, 128, 139, 163, 170, 261, 280 Peripheral stem cell transplantation, 117, 280, 302 Peripheral stem cells, 252, 280 Peritoneal, 4, 60, 175, 221, 280 Peritoneal Cavity, 4, 221, 280 Peritoneal Dialysis, 4, 280 Peritoneum, 160, 270, 280, 281 Peritonitis, 89, 281 Pernicious, 135, 169, 269, 281 Pernicious anemia, 135, 169, 281 Peroxidase, 63, 220, 266, 281 Peroxide, 266, 281 Petroleum, 226, 250, 279, 281 Phagocyte, 42, 278, 281 Phagocytosis, 14, 34, 52, 56, 152, 281 Phallic, 248, 281 Pharmaceutical Preparations, 230, 245, 250, 281 Pharmacodynamic, 20, 281 Pharmacokinetic, 21, 281 Pharmacologic, 218, 253, 281, 302 Pharmacotherapy, 16, 281

Index 323

Pharynx, 260, 273, 281, 301 Phenotype, 19, 27, 281 Phenyl, 154, 281 Phenylalanine, 281, 303 Pheresis, 82, 115, 281 Phlebotomy, 48, 281 Phosphodiesterase, 280, 282 Phospholipases, 282, 295 Phospholipids, 42, 97, 246, 266, 282 Phosphorus, 175, 227, 282 Phosphorylase, 71, 282 Phosphorylase a, 71, 282 Phosphorylase Phosphatase, 282 Phosphorylated, 232, 282 Phosphorylation, 30, 34, 46, 282 Photocoagulation, 232, 282 Phycoerythrin, 145, 282 Physical Examination, 4, 11, 115, 118, 176, 282 Physiologic, 134, 169, 215, 224, 239, 253, 263, 269, 270, 282, 289 Physiology, 5, 50, 97, 228, 254, 274, 282 Pigment, 58, 161, 223, 269, 282 Pilot study, 54, 74, 282 Placenta, 131, 157, 247, 283, 286, 304 Plants, 215, 226, 227, 231, 232, 251, 264, 272, 276, 283, 285, 292, 294, 302 Plasma cells, 218, 272, 273, 283 Plasma protein, 136, 175, 215, 243, 283, 287, 294 Plasma Volume, 225, 283 Plasmapheresis, 115, 220, 283 Plasmin, 219, 283 Plasminogen, 19, 20, 29, 219, 283, 294 Plasminogen Activators, 283 Plasminogen Inactivators, 283, 294 Plasticity, 255, 283 Plastids, 277, 283 Platelet Activation, 44, 139, 283, 295 Platelet Aggregation, 217, 245, 258, 275, 280, 284 Platelet Count, 122, 284 Platelet Transfusion, 162, 284 Plateletpheresis, 69, 220, 284 Platinum, 231, 284 Pleura, 284 Pleural, 160, 284 Poisoning, 107, 227, 245, 250, 270, 273, 284 Polyethylene, 140, 155, 284 Polymerase, 61, 84, 284, 291 Polymerase Chain Reaction, 61, 284 Polymers, 144, 284, 287, 297

Polymorphic, 51, 284 Polymorphism, 19, 51, 284 Polypeptide, 147, 155, 170, 216, 217, 232, 244, 247, 256, 283, 284, 300, 307 Polysaccharide, 219, 230, 285 Polyunsaturated fat, 71, 105, 285 Population Density, 131, 156, 285 Porphyria, 48, 282, 285 Porphyria Cutanea Tarda, 282, 285 Posterior, 40, 217, 230, 231, 241, 271, 278, 285, 301 Postmenopausal, 26, 278, 285 Postnatal, 18, 285, 297 Postsynaptic, 274, 285, 295, 299 Potassium, 5, 11, 86, 90, 198, 285 Potentiates, 261, 285 Potentiating, 224, 285 Potentiation, 285, 295 Practice Guidelines, 199, 285 Precursor, 24, 218, 221, 231, 237, 241, 242, 244, 253, 276, 281, 283, 285, 287, 303 Predisposition, 10, 125, 139, 140, 285 Prednisolone, 8, 285 Presynaptic, 274, 286, 299 Presynaptic Terminals, 274, 286, 299 Prevalence, 50, 174, 286 Prion, 230, 286 Probe, 36, 52, 286 Progeny, 234, 286 Progesterone, 75, 286, 297 Progression, 25, 27, 30, 134, 218, 286 Progressive, 35, 148, 171, 221, 229, 231, 238, 241, 245, 253, 273, 283, 286, 290, 303 Proinsulin, 29, 286, 288 Projection, 238, 276, 277, 286 Proline, 232, 257, 286 Promoter, 16, 286 Prone, 125, 286 Prophylaxis, 8, 9, 11, 152, 286, 291, 305 Proportional, 277, 286 Prospective study, 6, 18, 69, 286 Prostate, 177, 224, 286, 303 Prostatitis, 177, 286 Protease, 29, 44, 216, 283, 287 Protease Inhibitors, 44, 287 Protein C, 42, 135, 136, 158, 215, 216, 220, 223, 247, 266, 287, 304 Protein S, 23, 38, 125, 224, 245, 250, 287 Protein Subunits, 38, 287 Proteinuria, 6, 8, 272, 274, 287 Proteolytic, 44, 216, 233, 247, 283, 287, 294 Prothrombin, 5, 20, 279, 287, 300

324 White Blood Cells

Prothrombin Time, 5, 20, 287 Protocol, 15, 18, 40, 43, 48, 50, 115, 287 Protons, 216, 257, 263, 287, 289 Proto-Oncogene Proteins, 278, 287 Proto-Oncogene Proteins c-mos, 278, 287 Protozoa, 234, 242, 270, 271, 287, 303 Protozoan Infections, 230, 287 Psoriasis, 31, 133, 232, 287, 291 Psychiatric, 36, 270, 288, 295 Psychiatry, 78, 96, 248, 288 Psychic, 288, 293 Psychology, 240, 288 Psychomotor, 227, 275, 288 Psychotherapy, 288, 289 Puberty, 288, 301 Public Health, 30, 198, 199, 223, 288 Public Policy, 197, 288 Pulmonary, 12, 35, 44, 61, 82, 216, 225, 226, 235, 244, 245, 254, 288, 298, 306 Pulmonary Artery, 225, 288, 306 Pulse, 49, 272, 288 Purgative, 264, 288 Purified Insulins, 286, 288 Purpura, 142, 154, 288 Purulent, 12, 213, 288 Pyelonephritis, 9, 177, 288 Pyogenic, 4, 277, 288 Q Quality of Life, 15, 148, 150, 151, 288 Quiescent, 35, 122, 127, 288 R Race, 15, 271, 288 Radiation therapy, 117, 186, 246, 249, 262, 263, 289, 302, 303, 307 Radioimmunoassay, 60, 289 Radiolabeled, 21, 263, 289, 307 Radiological, 159, 289 Radiology, 83, 88, 95, 289 Radiotherapy, 226, 241, 263, 289, 307 Randomized, 15, 118, 242, 289 Reactivation, 8, 289 Reagent, 41, 130, 131, 133, 136, 137, 138, 145, 156, 166, 289 Reassurance, 4, 289 Receptors, Serotonin, 289, 294 Recombinant, 34, 155, 289, 305 Recombination, 234, 289 Reconstitution, 31, 131, 142, 154, 157, 289 Rectal, 5, 148, 171, 290 Rectum, 5, 148, 171, 220, 226, 233, 240, 248, 249, 260, 264, 286, 290, 298 Recurrence, 10, 48, 224, 290

Reductase, 267, 290, 295 Refer, 1, 226, 233, 241, 248, 249, 256, 266, 274, 275, 276, 290 Refractometer, 136, 290 Refractory, 151, 242, 290 Regeneration, 46, 289, 290 Regimen, 8, 15, 242, 281, 290 Regression Analysis, 26, 290 Relapse, 8, 25, 45, 198, 290 Reliability, 123, 128, 290 Remission, 8, 15, 25, 148, 171, 224, 268, 290 Renal Artery, 258, 290 Renal failure, 27, 142, 154, 290 Renin, 27, 218, 290 Renin-Angiotensin System, 27, 290 Reperfusion, 17, 290, 291 Reperfusion Injury, 291 Repressor, 277, 291 Research Design, 26, 291 Respiration, 227, 271, 272, 291 Respiratory Paralysis, 213, 291 Restoration, 289, 290, 291, 306 Reticulocytes, 145, 146, 147, 245, 291 Retina, 231, 274, 275, 277, 291, 292 Retinitis, 180, 291 Retinoids, 291 Retinol, 102, 103, 291 Retroviral vector, 158, 291 Rheology, 173, 280, 291 Rheumatism, 62, 292 Rheumatoid, 12, 15, 31, 64, 86, 94, 108, 133, 278, 292 Rheumatoid arthritis, 12, 15, 31, 64, 86, 94, 133, 292 Ribonucleoside Diphosphate Reductase, 257, 292 Ribose, 214, 292 Rigidity, 268, 283, 292 Risk factor, 26, 28, 185, 186, 267, 286, 292 Rod, 223, 292 Root Planing, 7, 292 Rubber, 213, 292 Ryanodine, 75, 292 Rye, 5, 232, 245, 292 S Saline, 226, 292 Saliva, 162, 292 Salivary, 237, 240, 292, 298, 307 Salivary glands, 237, 240, 292 Saponins, 292, 297 Sarcoidosis, 185, 292 Sarcoma, 202, 292

Index 325

Scans, 62, 118, 293 Scatter, 138, 141, 147, 166, 293 Schizophrenia, 36, 293 Sclerosis, 221, 272, 293 Screening, 11, 20, 25, 28, 125, 139, 140, 174, 232, 279, 293, 304 Scrub Typhus, 82, 293 Second Messenger Systems, 275, 293 Secretion, 91, 236, 244, 256, 261, 262, 272, 293, 305 Secretory, 12, 274, 293, 299 Sediment, 293, 304 Segregation, 29, 222, 223, 289, 293 Seizures, 16, 40, 227, 244, 293, 296 Self Administration, 293 Self Medication, 9, 293 Semen, 6, 62, 63, 92, 96, 97, 242, 286, 293 Seminiferous tubule, 293, 296 Semisynthetic, 227, 232, 293 Senile, 278, 294 Sensitization, 14, 294 Sepsis, 6, 74, 93, 95, 249, 294 Septic, 74, 221, 294 Sequencing, 284, 294 Serine, 243, 287, 294 Serine Endopeptidases, 243, 294 Serine Proteinase Inhibitors, 294 Serologic, 259, 294 Serotonin, 72, 220, 232, 281, 289, 294, 303 Serous, 221, 243, 284, 294 Serpins, 44, 294 Serum Albumin, 83, 289, 294 Shock, 21, 135, 150, 169, 217, 294, 303 Shock, Septic, 135, 169, 294 Side effect, 5, 8, 16, 51, 78, 148, 162, 185, 186, 189, 198, 215, 220, 224, 237, 294, 302, 307 Sigmoid, 295 Sigmoidoscopy, 11, 295 Signal Transduction, 21, 33, 295 Signs and Symptoms, 4, 15, 174, 290, 295 Silicon, 41, 295 Silicon Dioxide, 295 Simvastatin, 24, 295 Skeletal, 90, 272, 295 Skeleton, 214, 247, 263, 295 Skull, 236, 295, 300 Sleep Deprivation, 93, 96, 295 Small intestine, 148, 171, 223, 229, 231, 241, 244, 251, 256, 258, 262, 295 Smooth muscle, 216, 217, 227, 235, 256, 290, 295, 298

Social Environment, 288, 295 Sodium, 11, 17, 90, 175, 245, 295, 296, 305 Sodium Channels, 296, 305 Soft tissue, 176, 225, 295, 296 Solid tumor, 150, 151, 218, 296 Solvent, 223, 245, 252, 277, 296 Somatic, 256, 269, 271, 296 Soybean Oil, 285, 296 Spatial disorientation, 241, 296 Specialist, 6, 203, 240, 296 Species, 4, 9, 11, 42, 76, 125, 216, 230, 236, 237, 241, 244, 250, 253, 256, 268, 269, 271, 272, 273, 277, 279, 288, 296, 297, 298, 303, 306, 307 Specificity, 32, 35, 170, 215, 220, 243, 294, 296 Sperm, 53, 97, 100, 148, 231, 293, 296 Spermatozoa, 68, 97, 293, 296 Spinal cord, 25, 46, 222, 226, 230, 231, 241, 243, 269, 274, 275, 278, 291, 296, 298 Spirochete, 296, 299 Spleen, 100, 202, 237, 267, 292, 296 Splenectomy, 84, 257, 296 Splenomegaly, 257, 260, 296 Sputum, 160, 296 Staging, 143, 293, 296 Standard therapy, 150, 296 Status Epilepticus, 39, 296 Stem cell transplantation, 117, 297 Stem Cells, 33, 40, 47, 127, 132, 142, 154, 157, 245, 280, 297, 304 Sterile, 7, 13, 40, 221, 297 Sterility, 62, 63, 92, 97, 150, 237, 260, 297 Steroid, 8, 50, 78, 80, 146, 236, 292, 295, 297 Stimulant, 226, 236, 256, 297, 299 Stimulus, 241, 242, 246, 262, 264, 297, 300 Stomach, 148, 171, 213, 224, 240, 244, 245, 250, 251, 256, 273, 280, 281, 295, 296, 297 Stomatitis, 8, 297 Stool, 11, 25, 176, 247, 264, 297, 300 Strand, 56, 59, 64, 66, 67, 70, 74, 87, 100, 233, 284, 297 Streptococcal, 10, 265, 297 Streptococci, 4, 297 Streptococcus, 4, 297 Stress, 4, 6, 42, 52, 161, 176, 228, 236, 250, 273, 278, 285, 292, 297 Stroke, 16, 17, 28, 37, 88, 93, 120, 151, 196, 228, 255, 263, 297 Stromal, 33, 225, 297 Stromal Cells, 33, 225, 297 Styrene, 63, 71, 292, 297

326 White Blood Cells

Subacute, 260, 297 Subarachnoid, 253, 298 Subclinical, 260, 293, 298 Subcutaneous, 129, 242, 298, 306 Submaxillary, 244, 298 Subspecies, 296, 298 Substance P, 225, 245, 270, 290, 293, 298 Substrate, 39, 141, 159, 244, 257, 298 Suction, 247, 298 Sulfur, 73, 165, 264, 270, 298 Superantigens, 31, 298 Superoxide, 34, 91, 298 Supplementation, 57, 140, 298 Suppositories, 250, 298 Suppression, 91, 122, 125, 129, 236, 298 Surfactant, 18, 135, 298 Suspensions, 88, 298 Sympathetic Nervous System, 275, 298 Symphysis, 286, 298 Symptomatic, 9, 298 Symptomatology, 294, 299 Synapses, 140, 274, 275, 299 Synaptic, 275, 295, 299 Synaptic Transmission, 275, 299 Synaptic Vesicles, 299 Syncope, 40, 299 Synovial, 15, 177, 299 Synovial Fluid, 15, 177, 299 Synovial Membrane, 299 Syphilis, 76, 299 Systemic disease, 4, 299 Systemic lupus erythematosus, 39, 64, 133, 299 Systolic, 257, 299 T Tachycardia, 222, 299 Tachypnea, 222, 299 Tacrine, 140, 299 Technetium, 65, 92, 95, 100, 300 Teichoic Acids, 253, 300 Telomere, 48, 89, 92, 300 Telophase, 270, 300 Temporal, 52, 254, 300 Tenesmus, 241, 300 Tetanus, 300, 303 Thalassemia, 95, 142, 154, 255, 300 Thalidomide, 21, 92, 300 Therapeutics, 50, 165, 191, 300 Thermal, 80, 221, 240, 275, 284, 300 Thigh, 247, 253, 300 Thorax, 213, 267, 300 Threshold, 138, 257, 300

Thrombin, 20, 247, 284, 287, 300, 301 Thrombin Time, 20, 300 Thrombocytes, 166, 284, 301 Thrombocytopenia, 23, 142, 154, 301 Thrombolytic, 283, 301 Thrombomodulin, 287, 301 Thromboplastin, 287, 301 Thrombosis, 20, 68, 83, 84, 261, 287, 297, 301 Thrombus, 236, 260, 263, 284, 301 Thymidine, 118, 226, 301 Thymus, 73, 118, 202, 259, 267, 301 Thymus Gland, 202, 301 Thyroid, 161, 175, 185, 262, 301, 303 Thyroid Gland, 301 Thyroxine, 215, 281, 294, 301 Tissue Culture, 12, 301 Tolerance, 10, 21, 214, 251, 301 Tomography, 105, 301 Tonicity, 263, 301 Tonsil, 118, 301 Tooth Preparation, 214, 301 Topical, 221, 232, 245, 279, 302 Topotecan, 94, 302 Total-body irradiation, 117, 302 Toxic, iv, 17, 131, 135, 149, 157, 166, 169, 215, 223, 232, 234, 237, 238, 243, 253, 258, 275, 292, 297, 302, 307 Toxicity, 8, 16, 46, 241, 270, 302 Toxicology, 55, 63, 73, 85, 100, 148, 198, 302 Toxins, 175, 219, 243, 260, 272, 302 Toxoplasmosis, 97, 180, 302 Trace element, 295, 302 Trachea, 226, 269, 281, 301, 302 Transaminases, 175, 302 Transcriptase, 29, 213, 264, 302, 307 Transduction, 295, 302 Transfection, 51, 224, 302 Transfer Factor, 258, 302 Transfusion, 14, 32, 76, 86, 91, 94, 127, 140, 142, 154, 162, 202, 246, 302 Transient Ischemic Attacks, 40, 302 Translation, 245, 302 Translational, 18, 50, 302 Translocation, 245, 303 Transmitter, 213, 222, 241, 262, 269, 274, 276, 299, 303 Transplantation, 31, 33, 58, 96, 116, 131, 142, 154, 157, 163, 231, 258, 280, 303 Trauma, 68, 142, 154, 273, 303 Triage, 159, 303

Index 327

Trichomoniasis, 270, 303 Triglyceride, 24, 257, 303 Trismus, 186, 303 Trophoblast, 125, 224, 303 Trypanosomiasis, 143, 155, 303 Tryptophan, 233, 294, 303 Tuberculosis, 12, 35, 235, 267, 303 Tumor marker, 216, 224, 303 Tumor Necrosis Factor, 15, 80, 91, 158, 300, 303 Tumour, 80, 303 Typhoid fever, 95, 303 Tyrosine, 42, 241, 303 U Ulcer, 303 Ulceration, 72, 96, 272, 303 Ulcerative colitis, 95, 148, 171, 176, 260, 304 Ultrafiltration, 13, 175, 254, 304 Umbilical Arteries, 304 Umbilical Cord, 131, 157, 231, 304 Umbilical cord blood, 131, 157, 304 Unconscious, 238, 258, 304 Univalent, 257, 278, 304 Unresectable, 46, 304 Uranium, 300, 304 Urea, 76, 175, 225, 304 Uremia, 290, 304 Ureters, 262, 264, 290, 304 Urethra, 280, 286, 304 Uric, 175, 216, 304 Urinalysis, 6, 10, 12, 136, 175, 304 Urinary tract, 4, 6, 7, 9, 10, 137, 177, 223, 304 Urinary tract infection, 6, 7, 9, 10, 137, 177, 223, 304 Urine, 4, 6, 7, 8, 9, 10, 12, 18, 20, 24, 42, 45, 75, 92, 136, 137, 160, 177, 223, 224, 233, 236, 241, 244, 251, 254, 262, 264, 287, 304 Urine Testing, 4, 304 Urocanic Acid, 69, 305 Urogenital, 250, 305 Urologist, 4, 305 Uroporphyrinogen Decarboxylase, 48, 285, 305 Uterus, 230, 236, 238, 243, 270, 286, 305 V Vaccination, 21, 47, 305 Vaccine, 21, 35, 168, 180, 214, 227, 287, 305 Vacuoles, 222, 277, 305 Vagina, 117, 227, 230, 270, 305 Vaginal, 61, 117, 305

Valproic Acid, 16, 305 Valves, 159, 305 Vascular endothelial growth factor, 21, 46, 305 Vasoactive, 23, 305 Vasodilation, 50, 258, 305 Vasodilator, 226, 241, 256, 305 VE, 21, 305 Vector, 33, 129, 158, 302, 305 Vein, 115, 118, 218, 262, 276, 279, 281, 304, 305 Venereal, 299, 305 Venous, 36, 56, 72, 79, 96, 130, 159, 225, 265, 284, 287, 305 Venous blood, 36, 56, 130, 159, 225, 265, 284, 305 Ventricle, 235, 288, 299, 306 Ventricular, 17, 27, 50, 235, 306 Ventricular fibrillation, 17, 306 Venules, 52, 139, 225, 227, 243, 306 Vertebrae, 296, 306 Veterinary Medicine, 124, 160, 197, 306 Villous, 229, 306 Viral, 31, 33, 36, 57, 91, 125, 129, 134, 142, 177, 243, 251, 260, 277, 302, 306, 307 Viremia, 294, 306 Virulence, 16, 222, 224, 302, 306 Virulent, 22, 306 Virus, 8, 10, 22, 29, 31, 36, 64, 71, 107, 118, 129, 134, 143, 151, 155, 163, 179, 180, 202, 213, 223, 230, 244, 250, 251, 256, 260, 261, 291, 302, 306 Visceral, 281, 306 Vitro, 14, 21, 22, 33, 35, 38, 42, 44, 47, 49, 62, 68, 75, 80, 87, 89, 90, 94, 133, 142, 146, 148, 154, 155, 158, 216, 224, 229, 255, 259, 284, 301, 306 Vivo, 21, 22, 26, 33, 35, 37, 42, 44, 47, 48, 49, 59, 67, 69, 78, 93, 101, 130, 142, 146, 154, 155, 158, 216, 224, 255, 259, 278, 306 W Waist circumference, 29, 306 Warts, 256, 306 Windpipe, 281, 301, 306 Wound Healing, 28, 229, 261, 306 X Xanthine, 216, 306, 307 Xanthine Oxidase, 216, 307 Xenograft, 218, 307 Xerostomia, 186, 307 X-ray, 45, 51, 118, 234, 248, 249, 262, 263, 268, 272, 276, 289, 293, 307

328 White Blood Cells

X-ray therapy, 263, 307 Y Yeasts, 6, 249, 281, 307

Z Zalcitabine, 264, 307 Zygote, 234, 307 Zymogen, 287, 307

Index 329

330 White Blood Cells

Index 331

332 White Blood Cells