HERPES SIMPLEX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Herpes Simplex: 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: 0-597-83983-2 1. Herpes Simplex-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on herpes simplex. 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 HERPES SIMPLEX ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Herpes Simplex ............................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed .............................................................................. 100 CHAPTER 2. NUTRITION AND HERPES SIMPLEX ........................................................................... 147 Overview.................................................................................................................................... 147 Finding Nutrition Studies on Herpes Simplex .......................................................................... 147 Federal Resources on Nutrition ................................................................................................. 155 Additional Web Resources ......................................................................................................... 155 CHAPTER 3. ALTERNATIVE MEDICINE AND HERPES SIMPLEX ..................................................... 157 Overview.................................................................................................................................... 157 National Center for Complementary and Alternative Medicine................................................ 157 Additional Web Resources ......................................................................................................... 165 General References ..................................................................................................................... 170 CHAPTER 4. DISSERTATIONS ON HERPES SIMPLEX ....................................................................... 171 Overview.................................................................................................................................... 171 Dissertations on Herpes Simplex ............................................................................................... 171 Keeping Current ........................................................................................................................ 175 CHAPTER 5. CLINICAL TRIALS AND HERPES SIMPLEX ................................................................. 177 Overview.................................................................................................................................... 177 Recent Trials on Herpes Simplex ............................................................................................... 177 Keeping Current on Clinical Trials ........................................................................................... 189 CHAPTER 6. PATENTS ON HERPES SIMPLEX ................................................................................. 191 Overview.................................................................................................................................... 191 Patents on Herpes Simplex ........................................................................................................ 191 Patent Applications on Herpes Simplex .................................................................................... 215 Keeping Current ........................................................................................................................ 247 CHAPTER 7. BOOKS ON HERPES SIMPLEX ..................................................................................... 249 Overview.................................................................................................................................... 249 Book Summaries: Federal Agencies............................................................................................ 249 Book Summaries: Online Booksellers......................................................................................... 253 The National Library of Medicine Book Index ........................................................................... 255 Chapters on Herpes Simplex ...................................................................................................... 256 CHAPTER 8. MULTIMEDIA ON HERPES SIMPLEX .......................................................................... 271 Overview.................................................................................................................................... 271 Video Recordings ....................................................................................................................... 271 Audio Recordings....................................................................................................................... 271 Bibliography: Multimedia on Herpes Simplex........................................................................... 272 CHAPTER 9. PERIODICALS AND NEWS ON HERPES SIMPLEX ....................................................... 275 Overview.................................................................................................................................... 275 News Services and Press Releases.............................................................................................. 275 Newsletter Articles .................................................................................................................... 278 Academic Periodicals covering Herpes Simplex ........................................................................ 279 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 281 Overview.................................................................................................................................... 281 U.S. Pharmacopeia..................................................................................................................... 281 Commercial Databases ............................................................................................................... 283 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 287
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Overview.................................................................................................................................... 287 NIH Guidelines.......................................................................................................................... 287 NIH Databases........................................................................................................................... 289 Other Commercial Databases..................................................................................................... 292 APPENDIX B. PATIENT RESOURCES ............................................................................................... 293 Overview.................................................................................................................................... 293 Patient Guideline Sources.......................................................................................................... 293 Finding Associations.................................................................................................................. 299 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 303 Overview.................................................................................................................................... 303 Preparation................................................................................................................................. 303 Finding a Local Medical Library................................................................................................ 303 Medical Libraries in the U.S. and Canada ................................................................................. 303 ONLINE GLOSSARIES................................................................................................................ 309 Online Dictionary Directories ................................................................................................... 312 HERPES SIMPLEX DICTIONARY............................................................................................. 315 INDEX .............................................................................................................................................. 403
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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 herpes simplex 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 herpes simplex, 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 herpes simplex, 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 herpes simplex. 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 herpes simplex, 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 herpes simplex. 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 HERPES SIMPLEX Overview In this chapter, we will show you how to locate peer-reviewed references and studies on herpes simplex.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and herpes simplex, 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 “herpes simplex” (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: •
Diagnosis and Management of Recurrent Herpes Simplex Infections Source: JADA. Journal of the American Dental Association. 133(9): 1245-1249. September 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Dentists are frequently asked by patients to diagnose and treat recurrent herpes infections, which are painful and disfiguring. This article explores the diagnosis and treatment of these commonly encountered viral conditions. Herpetic infections represent a reactivation of the herpes simplex virus, which is highly infectious to patients, their families, dentists, and staff members. The diagnosis of these conditions usually is based on case-specific historical findings, the characteristic clinical
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appearance, and the location of the lesions. Dentists often treat patients with a history of recurrent herpetic infections. Currently used topical antiviral agents, when used in a timely manner, are well-absorbed and quite effective in decreasing the severity and duration of herpetic episodes. The author stresses that until the herpetic lesions are completely healed, the dental team and patient should use management strategies to prevent spread of the virus, ensure adequate nutrition, and maintain appropriate oral hygiene practices. 3 figures. 1 table. 19 references. •
Case Study: Herpes Labialis Source: Access. 16(1): 38-42. January 2002. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: Herpes viruses are a group of DNA viruses that cause oral and systemic diseases. Eight types of human herpes viruses have been identified. This article describes a case report of herpes labialis (commonly known as fever blister or cold sores) confined to the vermilion (red) of the mandibular (lower) lip. Diagnosis and management of the condition were performed primarily by the client who had been educated to work with the dental receptionist and dental hygienist to schedule oral health care appropriately. The client, a 44 year old female, presented to a general dentistry practice with a known history of herpes labialis. She was hoping to find better ways to prevent recurrent lesions during times of higher exposure to ultraviolet radiation (sunlight). The author describes the patient's treatment plan that included pretreatment with acyclovir ointment and oral acyclovir; each was used at a different time. The author also discusses the importance of working closely with patients who have the knowledge, experience, and motivation that helps facilitate oral health education and care. The outcome for this patient remains to be seen, but the client left the dental practice feeling satisfied that her concern was taken seriously and addressed appropriately. 2 figures. 25 references.
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Update on Treatments for Oral Herpes Simplex Viral Infections (Cold Sores and Fever Blisters) Source: Today's Therapeutic Trends: The Journal of New Developments in Clinical Medicine. 19(1): 39-58. 1st Quarter 2001. Contact: Available from Communications Media for Education, Inc. PO Box 712, Princeton Junction, NJ 08550. (800) 221-3899. Fax (609) 275-8745. Website: www.cmeglobal.com. Summary: Infection with herpes simplex virus (HSV) 1 or 2, which causes cold sores or fever blisters on the mouth, is common and usually mild. This article offers an update on the treatments used for oral herpes simplex viral infections. Unlike other common viral infections, infection with HSV is lifelong. Recurrent outbreaks are troublesome and treatment has typically been limited to palliation of symptoms. However, recent advances in antiviral therapies, most notably a new non prescription (over the counter) agent docosanol (Abreva), promise to provide many more patients with effective treatment alternatives for cold sores. The author reviews the transmission and pathogenesis of HSV 1, the clinical manifestations of HSV 1 infection (during the stages of initial outbreaks, latency, and recurrence), diagnosis, and treatment options, including prescription and nonprescription treatments. The author notes that for most people, the social and emotional impact of herpes is greater than the physical distress. Patients need support and education in making an educated choice about treatment
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options. Appendices include information about practical treatment and transmission issues, answers to frequently asked questions about herpes simplex, and a list of web sites with information on herpes simplex. 2 tables. 42 references. •
Differentiating Herpes Simplex Virus and Recurrent Aphthous Ulcerations Source: Access. 17(2): 30-34. February 2003. Contact: Available from American Dental Hygienists' Association (ADHA). 444 North Michigan Avenue, Chicago, IL 60611. (312) 440-8900. E-mail:
[email protected]. Website: www.adha.org. Summary: Recurrent oral ulcerations are commonly seen in dental office settings and are a source of discomfort and frustration for clients. It is often a challenge to distinguish one type of ulceration from another. Recurrent herpes simplex virus (HSV) and recurrent aphthous stomatitis (RAS) represent a classic example of lesions that are similar in clinical presentation and course. This article discusses the features of both ulcerative conditions, so dental hygienists can learn to differentiate between them. The author notes that these conditions share more similarities than differences clinically and thus are easy to misdiagnose. The author also discusses treatment considerations for each disease. 2 figures. 30 references.
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Salivary Defense Factors in Herpes Simplex Virus Infection Source: Journal of Dental Research. 81(6): 416-421. June 2002. Contact: Available from International Association for Dental Research. Subscription Department, 1619 Duke Street, Alexandria, VA 22314. (703) 548-0066. Fax (703) 548-1883. Summary: Saliva may contribute to a lowering of the infectious herpes simplex virus (HSV) dose during transmission and consequently abrogate infection or lead to decreased reactivation. To test this hypothesis, the authors of this article tested saliva for innate defense factors, immunoglobulin content, and the capacity to interfere with HSV infection. Serum or salivary anti-HSV IgG levels did not correlate with control of recurrent labial herpes (RLH) and were significantly higher in subjects with RLH compared with asymptomatic seropositive subjects. Although no differences in levels or output rate of innate defense factors between the groups were observed, the salivary neutralizing activity correlated with lactoferrin and hypothiocyanite concentrations in the asymptomatic seropositive group. The authors conclude that saliva contains factors, in addition to anti-HSV immunoglobulins, that neutralize HSV and may indirectly contribute to the control of RLH. 2 figures. 2 tables. 26 references.
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Effective Treatment of Herpes Simplex Labialis with Penciclovir Cream: Combined Results of Two Trials Source: JADA. Journal of the American Dental Association. 133(3): 303-309. March 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: This article reports on the combined results of two randomized, double blind, parallel group clinical trials that were conducted in Europe and North America to compare the efficacy and safety of topical 1 percent penciclovir cream with a placebo cream to treat herpes simplex labialis (cold sores on the lips). A total of 4,573 immunocompetent people with a history of recurrent herpes simplex labialis (HSL), with three or more episodes a year that typically manifested as classical lesions, were
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enrolled and prospectively dispensed medication: either 1 percent penciclover in a cetomacrogol cream base or a matching placebo. Patients self-initiated treatment and were required to apply study medication six times per day for the first day and every two hours while awake for four consecutive days. Of the 4,573 enrolled patients, 3,057 initiated treatment (1,516 with penciclovir and 1,541 with placebo). Combined data from two trials revealed that penciclovir recipients lost classical lesions 31 percent faster than did placebo recipients and experienced 28 percent faster resolution of lesion pain. Significant benefits were achieved with penciclovir use whether treatment was initiated in the early stages or the later stages. The authors conclude that penciclovir cream positively affects recurrent HSL, and dose frequency is vital to topical treatment. Even when penciclovir was applied late, it was effective in favorably altering the course of recurrent HSL. 4 tables. 14 references. •
Herpes Simplex Virus: Clinical Presentation and Treatment Source: Dentistry Today. 20(5): 65-67. May 2001. Contact: Available from Dentistry Today Inc. 26 Park Street, Montclair, NJ 07042. (973) 783-3935. Summary: This continuing education article familiarizes dental practitioners with the clinical presentation and treatment of herpes simplex virus (HSV). Topics include the virus and its pathogenesis, transmission, diagnosis, clinical presentation (symptoms), treatment of orolabial (mouth and lips) HSV infections, and the pharmacological (drug) treatment of orolabial HSV infections. The author stresses that practitioners should be aware of the 'asymptomatic virus shedding' phenomenon, in which a patient with HSV who does not have clinical symptoms is contagious approximately 4 percent of the time. Treatment with acyclovir (Zovirax) and valacyclovir (Valtrex) is common, however, neither product is labeled for use in orolabial herpes. Other treatment strategies include counseling the patient to determine infection triggers, modify lifestyle to reduce those triggers, wear a wide brimmed hat and use a sunscreen with greater than SPF 30, and consider the use of drug agents during the prodrome (preblister) stage. A brief posttest for continuing education credits is appended to the article. 2 tables. 13 references.
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Herpes Simplex Virus Type 1 in Brain and Risk of Alzheimer's Disease Source: Lancet. 349: 241-244. January 25, 1997. Summary: This journal article describes a possible association between herpes simplex virus type 1 (HSV1) and apolipoprotein E4 (apoE4) in Alzheimer's disease (AD). Researchers studied 84 brain samples from 46 AD patients and 75 brain samples from 44 people without dementia. DNA was extracted from the brain samples, and polymerase chain reaction (PCR) amplification was used to detect the HSV1 thymidine kinase gene and the host apoE gene. Multiple regression analysis suggests that the apoE4 allele frequency was significantly higher in AD patients positive for HSV1 in the brain (58.8 percent) than in the HSV1-negative AD group (10 percent), the HSV1-positive nondementia group (3.6 percent), or the HSV1-negative nondementia group (6.3 percent). The odds ratio for apoE4 compared with the HSV1-negative nondementia group was 16.8 in the HSV1-positive AD group, 1.67 in the HSV1-negative AD group, and 0.56 in the HSV1-positive nondementia group. In a separate comparison of apoE gene statuses in 40 people with and 33 without recurrent cold sores, the apoE4 allele frequencies were 36 percent and 9 percent, respectively. The authors conclude that the combination of HSV1 in the brain and the presence of an apoE4 allele appears to be a strong risk factor for AD. 1 figure, 5 tables, 26 references. (AA-M).
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Federally Funded Research on Herpes Simplex The U.S. Government supports a variety of research studies relating to herpes simplex. 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 herpes simplex. 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 herpes simplex. The following is typical of the type of information found when searching the CRISP database for herpes simplex: •
Project Title: A FEMALE MOUSE MODEL TO STUDY RECURRENT GENITAL HERPES Principal Investigator & Institution: Parr, Margaret B.; Professor; Anatomy; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: The purpose of this research is to further our understanding of immunity to sexually transmitted herpes simplex virus type 2 (HSV-2). In women, HSV-2 infects the mucosa in the genital tract and spreads to the nervous system where it persists in sensory ganglia as latent virus. Under conditions of stress, latent virus is activated and causes recurrent disease. Development of a vaccine to prevent HSV-2 infections in the genital tract and subsequent latency is problematic because it requires sterile immunity, but factors that suppress reactivation of latent irus deserve thorough investigation. The only animal model for studies of recurrent herpetic disease in the genital tract uses the guinea pig, but this species is less suitable for immunologic studies than mice. We propose experiments to establish a mouse model for studies of genital recurrent herpetic disease. The aims of this proposal are: Specific Aim 1: Tod etermine whether treatment with acyclovir and/or passive transfer of polyclonal HSV-2 antibody or monoclonal antibody to HSV- 2 glycoprotein D to naive mice after intravaginal infection with HSV-2 will prevent or attenuate neurological disease; Specific Aim 2: To demonstrate latent virus in lumbosacral ganglia in mice that survive infection. Specific Aim 3: To determine whether latently infected mice show spontaneous and induce recurrent infection. Specific Aim 4: To test the hypothesis that therapeutic immunization of latently infected mice will reduce or eliminate recurrent infection and to compare the effectiveness of vaccines that stimulate humoral immunity alone or both humoral and T cell mediated immunity. If therapeutic immunization reduced recurrent infections in women, it would reduce severe herpes infections in newborns, decrease the sexually transmitted spread of this virus throughout the population, and improve women's reproductive health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Project Title: AMELIORATION OF RECURRENT HERPES KERATITIS Principal Investigator & Institution: Stuart, Patrick M.; Assistant Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-MAY-2003 Summary: Herpes simplex keratitis is the leading cause of infectious blindness in the United States. Visual loss most commonly results from recurrent stromal disease, as opposed to primary herpes keratitis. Most experimental models have focused on primary rather than recurrent keratitis. The PI has created an animal model of recurrent herpetic keratitis in humans. The focal stromal opacification, regional neovascularization and endotheliitis produced in the recurrent keratitis model, is in distinct contrast to the keratinization, limbus to limbus opacification and exudative blepharoconjunctivitis that is seen in primary herpes simplex keratitis in NIH mice. While current data indicates that primary and recurrent herpes keratitis may share some common immune mechanisms, it is the PI's hypothesis that the considerable differences in the clinical pathology, viral antigen distribution within the cornea, and responses to vaccine therapy suggests that the immune responses in these two diseases will not be identical. The PI has proposed studies designed to test the hypothesis that recurrent HSK in NIH inbred mice is mediated by CD4+ T cells of the Th1 phenotype. In order to test this hypothesis he will: (1) define the cellular and costimulatory requirements for recurrent disease by selective depletion experiments; (2) characterize and compare the cytokine profile in corneal tissue during primary versus recurrent keratitis, using ELISA and RT-PCR analysis and then determine the relevance of these cytokines to recurrent disease by specifically targeting cytokines with monoclonal antibodies; (3) determine whether protective vaccination with a vhs-mutant strain of HSV-1 involves the selective stimulation of a Th2-mediated immune response. The information derived from these studies will lead to a better understanding of the biology of recurrent herpes simplex keratitis in mice and thereby this disease in humans. Furthermore, these studies could possibly suggest more specific and effective immunotherapies designed to ameliorate herpes simplex keratitis disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF HSV 1 TEGUMENT PROTEINS AND VIRUS ASSEMBLY Principal Investigator & Institution: Courtney, Richard J.; Professor; Microbiology and Immunology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-JAN-1978; Project End 31-JAN-2006 Summary: The long-term goals of the research efforts within our laboratory have been to define the biochemical and immunological properties of selected herpes simplex virus (HSV) glycoproteins and tegument proteins and to provide new insight regarding their synthesis, processing, interactions, and functional roles within HSV-infected cells. As a significant extension to these studies, the overall objective of this competitive renewal application is to define the roles HSV-1 tegument and integral membrane proteins play in the envelopment/budding process. The working hypothesis for the proposed studies is that one or more specific tegument proteins are major participants in the initiation of the envelopment process (i.e. budding). It is also part of the working hypothesis that enveloped viruses in general are likely to use similar mechanisms to accomplish the envelopment process. The expertise and experience of two laboratories (Courtney and
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Wills) will join to address the goals of the project. The Courtney laboratory has for a number of years studied various aspects of HSV glycoproteins and tegument proteins. The Wills laboratory has defined, at the molecular level, specific amino acid domains that are responsible for the envelopment and budding of retroviruses. The proposed studies includes four specific aims that are interrelated, but are independent of each other. The first aim will focus on the expression and targeting of individual tegument proteins. Our working hypothesis is that targeting information within these tegument proteins plays a key role in the tegumentation of virus particles at internal membranes within virus-infected cells. These studies will dissect the targeting domains of tegument proteins and provide new insight as to what controls their localization within the cell. The second aim will-focus on the identification of the minimal budding machinery of HSV-1. The working hypothesis is that a subset of tegument/membrane proteins has the potential to mediate the envelopment/budding process. Two experimental approaches will be used. The first is to express selected tegument proteins, both individually and m various combinations and to determine if these proteins can mediate envelopment and egress of virus particle/vesicles into the media. In the second approach, the Rous sarcoma virus Src membrane-binding domain fused to tegument proteins will be used to target these proteins to the plasma membrane. This approach will allow us to investigate envelopment and release of enveloped particles from the plasma membrane and thus bypass events associated with the egress of enveloped particles to the extracellular space. The third aim focuses on the molecular dissection of two tegument proteins as an approach to define the packaging events that occur during assembly. The fourth aim will focus on the identification of retroviral M (membrane binding) and L (late) domain equivalents within HSV-1 tegument proteins. Recent studies have suggested that late domains interact with specific domains of cellular proteins and are required for the virus-cell separation event ("pinching off'). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGEN MODULATION OF T CELL CYTOKINE PROFILE Principal Investigator & Institution: Evavold, Brian D.; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: The overall theme of this project is to identify the extent to which analogs of immunogenic peptide can influence and alter the phenotype of T helper cells. This is important not just for manipulation of the immune response, but also to deepen our understanding of the mechanisms responsible for the polarization of response towards a Th1 or Th2 phenotype. The fundamental hypothesis of this study is that the phenotype of T cells (cytokine response) will vary as a function of the stimulatory peptide ligand. In the following three aims, the goals are to identify mechanisms by which peptide shifts precursor Th0 cells in vitro (aim I), extend this information to model antigens in vivo (aim II), and apply our findings to a viral pathogen (aim III). AIM I- Analysis of the effect of partial agonists/ antagonists peptide variants on the differentiation of Th0 cells in vitro. The hypothesis underlying this aim is that analogs of immunogenic peptide can selectively activate Th0 cell functional responses and promote the differentiation into a defined Th1 or Th2 phenotype. The experimental approach will focus on three possible mechanisms by which peptide could drive the differentiation of Th0 clones which are: 1) the selective down-modulation of the IL-2 response (an anergic state), 2) the specific activation of the Th2 cytokine profile, and 3) alter the effective dose of antigen (antagonism). AIM II- Analysis of the effect of partial agonists/ antagonists peptide variants on the differentiation of Th0 cells in vivo. This aim will test the hypothesis that
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analogs of immunogenic peptide can selectively influence the Th response in vivo. The experimental approach will be to inject altered peptide ligands of the well-defined model antigens from aim I into inbred and TCR transgenic mice and determine the Th phenotype and precursor T cell frequency. AIM III- Analysis of a Herpes simplex-1 viral epitope and manipulation of the phenotype of the T cell response. This aim will continue to test the hypothesis that antigen can control Th response in vivo with the additional factor of influencing the response to the herpes simplex-1 pathogen. The goal of these experiments will be to apply the protocol(s) identified in aims I and II to the multi-antigenic HSV-1 pathogen. These aims are expected to accomplish our broad objectives through the use of variants of antigenic peptides to manipulate and control the Th cell response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOPHAGY: A NOVEL ANTIVIRAL HOST DEFENSE PATHWAY Principal Investigator & Institution: Levine, Beth C.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The process of autophagy, or bulk degradation of cellular proteins through an evolutionarily conserved autophagosomic-lysosomal pathway, is important in survival during nutrient stress, differentiation and development, and negative growth control. However, almost nothing is known about the role of this cellular pathway in defense against intracellular pathogens. The broad objective of this proposal is to evaluate the novel hypothesis that autophagy functions as an intracellular antiviral pathway that degrades viral particles and is antagonized by viral gene products required for disease pathogenesis. In support of this hypothesis, we have previously shown that the first identified mammalian autophagy gene, beclin 1, inhibits Sindbis virus replication and protects mice against lethal Sindbis virus encephalitis. In addition, our recent data demonstrate that the well-characterized IFNinducible antiviral molecule, PKR, is required for herpes simplex virus (HSV)-induced autophagy and that the HSV-l-encoded neurovirulence gene product, ICP34.5, antagonizes PKR-dependent autophagy in mammalian cells and Beclin 1-dependent autophagy in yeast. Together, these findings lead us to hypothesize a role for Beclin 1dependent autophagy in antiviral host defense and a role for ICP34.5 antagonism of Beclin 1-dependent autophagy in neurovirulence. In this proposal, there are four specific aims that investigate related sub-hypotheses, including: (1) the beclin 1 autophagy gene is required for HSV-l-induced autophagy; (2) HSV-1 ICP34.5 antagonizes autophagy in virally-infected cells through a direct interaction with the Beclin 1 autophagy protein; (3) Beclin 1-dependent autophagy functions as an antiviral host defense pathway by facilitating the degradation of intracytoplasmic viral particles and this function of Beclin 1 is antagonized by ICP34.5; and (4) HSV ICP34.5 regulates HSV-1 neurovirulence through a mechanism that involves antagonism of Beclin 1-dependent autophagy. To accomplish these aims, we will use an approach involving the combined use of host cells that are deficient in autophagy and expression of Beclin 1 protein and recombinant HSV-1 viruses that encode ICP34.5 mutant proteins that are deficient in antagonism of Beclin 1-dependent autophagy. We will use these reagents to investigate the role of Beclin 1-dependent autophagy in regulating viral replication and the role of ICP34.5 antagonism of Beclin 1-dependent autophagy in regulating viral neurovirulence. Together, these studies will provide novel insights about the role of autophagy in antiviral host defense and the role of viral evasion of autophagy in neurovirulence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BACTERIAL ARTIFICIAL CHROMOSOMES FOR HSV GENOMICS Principal Investigator & Institution: Leib, David A.; Associate Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Herpes simplex virus (HSV) is a significant and common human pathogen. HSV is a leading cause of nontraumatic blindness in the US with an accompanying ocular diseases ranging from dendritic epithelial keratitis, conjunctivits and blepharitis, to blinding necrotizing stromal keratitis. In addition, HSV causes cold sores, genital sores, and is a leading cause of viral encephalitis. The use of defined genetic alterations has become standard in many fields to gain insight into the functions of genes. Such genetic approaches -are often cumbersome, with the generation of genetically altered organisms often being far more time-consuming than the actual analysis of genetic function itself. There is, therefore, a need for the application of novel technologies to speed up the generation of mutants. This is certainly the case for the herpes viruses whose large DNA genomes, although amenable to reverse genetics by homologous recombination, complicate the generation of defined mutants. The goal of this proposal is to harness the power of bacterial artificial chromosome (BAC) technology to make HSV amenable to bacterial genetic approaches. For some other herpes viruses, BAC technology allows the generation of several mutants in less than a week. This is in contrast to current HSV recombination methodologies that allow generation of a single mutant in 2-3 months. BACs will therefore be generated for each of the three major laboratory strains of HSV-1 and two strains of HSV-2. Prior to their use as templates for mutagenesis, viruses will be regenerated from each of these BACs and their phenotypes compared carefully to their original parental strains. This will ensure that the propagation of such viruses as BACs does not inherently cause any undefined changes in the gene expression profiles, virulence, or pathogenesis of any of these viruses. Once established and characterized these reagents will be deposited with ATCC to allow all researchers access to this powerful technology. This work will represent a major advance in the field in allowing the rapid generation of HSV mutants in a standardized fashion for basic research, as well as for vaccine, anti-tumor agent, and gene delivery vector development. The successful outcome of this proposal, consistent with the R03 program objectives and strategic goals of the NEI's Corneal Diseases Program, will have a major impact on the research of all laboratories working on HSV infections and their blinding sequelae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR MECHANISMS OF HSV REACTIVATION Principal Investigator & Institution: Greenberg, Michael E.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-JUL-2006 Summary: (provided by applicant): Herpes simplex virus (HSV) infections in humans result in sporadic but recurrent lesions that appear at the site of the initial infection, and are now known to be the result of the reactivation of latent virus that resides within sensory neurons. As a large percentage of the human population experience some form of HSV infection, this virus represents a significant health issue. In this application, we propose a series of experiments that will investigate the cellular mechanisms that control the reactivation of latent HSV in sensory neurons. Based on prior studies of the response of peripheral neurons to axotomy, and the finding that the axotomy of sensory neurons triggers HSV reactivation, we hypothesize that a combination of neurotrophin
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withdrawal and cytokine secretion triggers HSV reactivation. To test this hypothesis and to identify intracellular signaling mechanisms that control HSV reactivation, we propose the following aims: 1. To characterize the sensory neurons that support ESV reactivation from latency by examining the expression of neurotrophin and cytokine receptors in latently infected neurons that are induced to support HSV reactivation. 2. To use neurotrophins, cytokines, and specific blockers of these factors to examine whether neurotrophins and cytokines regulate HSV latency and reactivation. 3. To identify the intracellular signaling pathways that are activated by extracellular stimuli that induce HSV reactivation in latently infected neurons, and to determine if these specific pathways play a critical role in regulating HSV latency and reactivation. Taken together, these aims will provide new insight into the cellular mechanisms that control the reactivation of latent HSV and may allow the generation of new therapeutics that could help to inhibit the reactivation process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBINED GENE THERAPY FOR METASTATIC BREAST CANCER Principal Investigator & Institution: Ojeifo, John O.; Assistant Professor; V T Lombardi Cancer Res Center; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (provided by Applicant) Recurrence and metastatic dissemination of breast cancers account for a significant morbidity and mortality in women, and effective means of treating this subset of patients remains elusive. In his post-doctoral studies, John Ojeifo, M.D., Ph.D., developed a novel t h e rapeutic drug delivery system that utilizes genetically-engineered endothelial cells to treat a variety of diseases. In this Mentored Career Development Award application, the candidate outlines a plan that will enable him to mature into a fully independent investigator studying the therapeutic efficacy and safety of intravenously (IV)-administered, genetically-modified endothelial cells (GMECs) transduced to express a cytokine and a suicide transgenes in metastatic breast cancer-bearing mice. During years 1 and 2 of the award, the candidate will benefit from the co-mentorship of Dr. Marc Lippman, a renowned expert in breast cancer biology and treatment, and Dr. Esther Chang, an expert in gene therapy. By year 3, Dr. Ojeifo will be a fully independent investigator. The broad goal of this application is to establish an independent laboratory studying: (I) the molecular and cellular mechanisms contributing to immune dysfunction in human cancers, and (ii) devising novel strategies for effective and safe genetic therapy and prevention of human cancers. To this end, the applicant first plans to test the hypothesis that a mixture of endothelial cells stably expressing herpes simplex virus thymidine kinase (HSV-TK) and h u man interleukin-2 (hIL-2) transgenes can target sites of pulmonary metastasis of breast tumors, induce an anti-tumor immune response at the local site, and abrogate the tumors in mice. The Specific Aims of this proposal are: Aim 1: To construct a bicistronic retroviral vector containing herpes simplex virus thymidine kinase (HSV-TK) and E. coli lacZ genes with intervening IRES fragment, and generate endothelial cells expressing the HSV-TK and lacZ transgenes. Aim 2: To determine (a) How well murine endothelial cells expressing HSV-TK transgene can target metastatic sites of breast tumors, and (b) the effects of HSV-TK gene expression upon tumor metastasis and animal survival. Aim 3: To determine whether the administration of a mixture of hIL-2 genetically-modified endothelial cells (GMECs) and HSV-TK GMECs followed by ganciclovir treatment can induce an effective, specific, and long-term anti-tumor immune response, and abrogate lung metastasis of breast tumors in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROL OF VIRAL RNA SYNTHESIS IN HERPES VIRUS INFECTION Principal Investigator & Institution: Wagner, Edward K.; Professor of Virology; Molecular Biology and Biochem; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001; Project Start 15-MAY-1978; Project End 31-JAN-2006 Summary: The differential stability of interactions between kinetic classes of HSV promoters and the basal transcriptional machinery of the cell combined with virusmediated compartmentalization of transcription machinery does much to explain the selective expression and repression of various kinetic classes of viral genes during the different phases of the productive replication cycle. We will expand and validate this model by accomplishing the following: 1. Analyze the biochemical interaction between a class of strict late promoters that contain a downstream activating sequence (DAS), as exemplified by the UL38 promoter, and the DNA binding subunits (Ku) of the multifunctional cellular enzyme DNA-dependant phosphokinase (DNA-PK). A major feature of this investigation will be the use of cultured cells in which components of DNA-PK have been functionally deleted, and purified TFIID. 2. Choose model promoters to investigate other modes that HSV utilizes to directly stabilize the interaction between late promoters and the TFIID complex. HSV DNA micro-arrays will be developed for this study. 3. Investigate how the kinetic class-specific promoter structure of HSV transcripts influences the strength of binding of the pre-initiation complex to influence time of maximal expression. We will use purified TFIID for biochemical studies, as well as in situ hybridization methods for analysis of differential gene expression in individual cells. 4. Use cell culture and mouse pathogenesis models to study of the precise role of time and level of maximal expression of selected required viral genes. This work has been started with viruses expressing kinetic alterations in the major capsid protein (VP5). We will also study kinetic modifications of expression of the VP19 capsid protein, the virion trans- activating protein, and the immediate-early ICP 27 promoter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--HISTOPATHOLOGY AND MICROSCOPY Principal Investigator & Institution: Ishov, Alexander; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 31-AUG-2006 Summary: Description (provided by applicant) The Microscopy and Histopathology Laboratory provides a service to these members of the program project, whose work involves the evaluation of tissue or cell alterations that occur in response to HSV infection. Tissue will be embedded, sectioned, and stained. Microscopy services will be provided, including confocal microscopy. Dr Ehud Lavi, neuropathologist, will continue to provide anatomical advice on the sections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--LABORATORY Principal Investigator & Institution: Morrow, Rhoda A.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: The Virology Laboratory Core provides virologic, immunologic, and molecular laboratory testing for HSV and HIV in 3 well established, accredited
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diagnostic laboratories; each directed by University of Washington (UW) faculty involved in this Program Project: the UW Virology Laboratory at Children's Hospital and Medical Center (CHMC; directed by Dr. R Ashley), the UW Retrovirology Laboratory at University of Washington Health Sciences Center (directed by Drs. R. Coombs and L. Corey)) and the Molecular Virology Laboratory at the Fred Hutchinson Cancer Research Center (FHCRC; directed by Dr. L. Corey). The CHMC lab will perform HSV isolation, serology, and antiviral sensitivity testing to diagnose and characterize HSV infections in subjects enrolled in Project I-IV. The UW Retrovirology Lab will perform HSV PCR, in situ HSV PCR< and HSV restriction enzyme analyses. Lab testing at these 3 sites will be supplemented by specialized testing performed in the research laboratories of Dr. R. Ashley at CHMC (mucosal antibody testing) and Dr. D. Koelle at FHCRC (CD8+ pCTL testing). Testing performed in these 5 sites will follow uniform practices of quality assurance and quality control which are established and reviewed biannually by the College of American Pathologists for accreditation of our diagnostic testing services. Accesioning of specimens, specimen handling and banking, specimen retrieval, and reporting will be performed according to uniform guidelines to assure accurate test results as well as smooth electronic data transfer between laboratories and the data management team; between laboratories and investigators involved in Projects I-IV, and between data management and the Administrative Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--VECTOR 1--ADENOVIRUS/ADENO ASSOCIATED VIRUS HERPESVIRUS LIPOSOME Principal Investigator & Institution: Hackett, Neil R.; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: Core A (Vector 1) will provide assistance in the design, construction and struCtural verification of gene therapy vectors based on adenovirus (Ad), adenoassociated virus (AAV), herpes simplex virus I (HSV). The major role of the core is to provide knowledge and biological materials to the investigators so they may focus on the biological aspects of their projects rather than the technology of gene therapy. For this reason the core will fulfill the following roles: Perform large scale vector preparations for the participating projects (target 50 preparations /year) in accordance with the core usage allocations and resources available; Create new gene therapy vectors by importing improvements in the technology and / or new transgenes that are important for the participating projects (target 18 / year); Provide Standard Operating Procedures for all phases in the construction of all three types of viral vector; Education in construction of vectors through tutorials with senior core scientists and shadowing core technicians; Supply verified samples of biological materials for the vector construction including plasmids, cell lines and starting vectors, and maintain a database describing those materials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORNEAL DISEASE--MECHANISM OF LATENCY OF HSV-1 Principal Investigator & Institution: Mitchell, William J.; Assistant Professor; Veterinary Pathobiology; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The most common cause of infectious corneal blindness in humans in the developed world is herpes simplex virus induced keratitis. The available evidence
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indicates that HSV initiates and produces this corneal inflammatory disease. The pathogenesis of herpes stromal keratitis, requires that HSV-1 be maintained as a latent infection in the ophthalmic sensory neurons of the trigeminal ganglia and that it be periodically reactivated. The reactivated virus can either contribute to the corneal inflammatory disease or infect new hosts. the underlying basis of herpetic corneal disease is latent neuronal infection by HSV-1. The stimuli which cause reactivation of HSV usually involved changes in the physiology of the host cell. This coupled with a failure to demonstrate viral genes that control the latent and reactivated viral genome, leads to the hypothesis that neuronal transcriptional proteins control this process by activating or repressing viral immediate early (IE) gene expression. No suitable model for studying the regulation of HSV-1 latency exists in cultured cells. The application of transgenic technology offers a powerful way to test whether host transcriptional proteins control latent HSV infection of sensory neurons. The experiments described in this proposal are intended to delineate the underlying mechanism by which the virus is regulated by host cells during latent and reactivated infections. An understanding of this mechanism should lead to design of strategies or prevent HSV induced corneal disease. The objectives of these studies are: 1) Establish whether host transcriptional proteins can regulate HSV IE genes in neurons in vivo and whether viral IE genes can be regulated in a way that would be appropriate for controlling latent and reactivated infections. 2) Determine whether inhibition or stimulation of viral Ie gene expression will result in alteration of the ability of HSV to establish a latent infection and reactivate. 3)Determine whether host transcriptional regulatory proteins can modulate latent and reactivated HSV infections of sensory ganglia in tansgenic mouse models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DERG ENCEPHALITIS
(IMMUNOMODULATOR)
TREATMENT
OF
VIRAL
Principal Investigator & Institution: Rosenthal, Kenneth S.; Microbiology and Immunology; Northeastern Ohio Universities Coll Med P.O. Box 95 Rootstown, Oh 44272 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The ultimate goal of this program is to develop a prophylactic or therapeutic agent (derG) for treatment of medically important viral and other infections for which there may not be treatment or the treatment is too toxic. DerG was identified as a new immunostimulatory peptide as a result of work on L.E.A.P.S.TM vaccine technology. The derG peptide is based on sequence from the beta chain of the MHC II molecule and is an altered peptide ligand of the CD4 molecule. Preliminary studies in different laboratories indicate that derG can induce protection against parasitic malarial sporozoite and herpes simplex virus challenge and act as an adjuvant for tumor vaccine therapy. Administration of derG within 3 days (or less) or up to 4 weeks in advance of infectious challenge elicited protection against HSV challenge. The proposed investigation will extend our studies of derG on HSV and determine by using mouse models whether derG protects against viral encephalitis by HSV and an arbovirus, S.A. AR86 sindbis-Iike alphavirus. Our specific aims are to: 1) establish the efficacy of derG against these viruses; 2) develop in vitro assays for derG activity to allow screening of analogues, other drugs and to maximize potential for the following aims; 3) determine the mechanism of action of derG; 4) design and prepare for evaluation derG analogues in vitro and in HSV challenge models and initiate procedures required to pursue FDA approval of derG for human therapy. This project is part of a continued collaboration between an academician and CEL-SCI Inc., a
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biotechnology-vaccine development company. CEL-SCI is committed to provide support including technological development, quality control, scale up to GMP level development, access to preclinical development, methods for toxicological and pharmacological testing, clinical testing and data management resources. Successful development of derG may provide a broad spectrum, immunoenhancing prophylactic and therapeutic treatment that can be provided in lieu of, or to enhance vaccination prior to travel or assignment to a region of high risk for exposure to infectious or bioterror agents upon short notice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA VACCINE EFFIICACY IN HERPES SIMPLEX VIRUS TYPE 2 Principal Investigator & Institution: Bernstein, David I.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Adapted from Applicant's Abstract) Herpes simplex virus type 2 (HSV-2) infection is one of the most common sexually transmitted diseases. Following acute infection of the genital tract, the virus becomes latent and can reactivate to cause recurrent disease or be shed asymptomatically. Therefore vaccines can either be prophylactic, preventing or modifying the initial infection, or therapeutic, preventing or minimizing recurrent disease in those previously infected with HSV-2. To date neither vaccine strategy has been successful. One recent vaccine strategy utilizes DNA but this approach has not been optimized. In this application, we describe experiments designed to increase the effectiveness of HSV DNA vaccines. Because protection from both acute and recurrent HSV disease appears to be mediated by T cells, the initial aims are to evaluate HSV-2 glycoprotein B (gB) DNA vaccines targeted to the endosome/lysosome to increase MHC class II presentation and the CD4+ response (Aim 1). We also will characterize gB DNA vaccines targeted to the proteasome to increase MHC Class I presentation and the CD8+ T cell response (Aim 2). We will verify targeting, evaluate T cell responses, and assess these vaccines in our well-characterized small animal models of HSV-2 infection. In Aim 3, we will combine the best MHC class I and MHC class II targeted vaccines and evaluate their combined efficacy. In Aim 4, we will examine the effects of co-expressing gB with immune homing receptors. By targeting the antigen presenting cells to the lymph nodes we hypothesize that we will increase both the HSVspecific and innate immune response and protection. Our experience with the murine and guinea pig models as well as the virologic, clinical and immunologic endpoints make these models ideal for examining the strategies proposed. The experiments proposed will improve our understanding of the protective immune response for acute and recurrent disease, increase our knowledge of targeted DNA vectors for HSV-2 and other pathogens, and should result in improved DNA vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENGINEERED HERPES SIMPLEX VIRUS FOR TREATMENT OF GLIOMAS Principal Investigator & Institution: Markert, James M.; Professor; Surgery; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2002 Summary: The purpose of this Mentored Clinical Scientist Development Award application is to provide the necessary training for the principal investigator to develop into a fully independent investigator applying molecular medicine to diseases of the
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central nervous system (CNS). Specifically, the application proposes to engineer novel modifications into the genome of herpes simplex viruses (HSV) for the purpose of developing a safe and effective therapy for human gliomas. The development of these viruses will include foreign gene inserts to enhance the oncolytic activity of these viruses. Multiple genes from the HSV genome will he deleted to enhance the safety of this therapy. Double probes will be utilized to determine the distribution of both latent and actively replicating HSV in the CNS of treated animals. As virus constructs are developed, their biologic behavior will be evaluated in both in vitro and in vivo glioma models. This will include assessment of replication, antitumor activity, and the degree of foreign gene expression. In vivo evaluations will be conducted in both scid and c57BL/6 mice bearing intracranial gliomas to calculate the effects of immune response on tumor regression and host survival. Tissue sections will be examined to evaluate glioma eradication, neurovirulence, residual infectious virus, and immune response. Promising constructs will then be tested for neurovirulence in the HSV-sensitive simian primate, Aotus. The mentors who will direct this training proposal are international experts in herpes simplex virology and in glioma biology. The program is fully endorsed by the Division of Neurosurgery, which will provide all necessary resources. The candidate's career objective is to become a clinician-scientist who both 1) develops new models for the treatment of neurological diseases based on molecular medicine and 2) bridges basic science and clinical medicine by bringing such therapies into clinical use. An integral portion of the training program will thus be aimed at developing expertise in the design and administration of clinical trials. The candidate's immediate goals are to participate in an organized program that will provide the necessary training to become a fully independent investigator in this area while studying a novel therapy for brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIDELITY OF HERPES SIMPLEX VIRUS DNA REPLICATION Principal Investigator & Institution: Hwang, Charles B.; Microbiology and Immunology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-DEC-2002 Summary: Herpes simplex viruses (HSV) are important pathogens affecting more than 50% of the general population HSV infections can cause aggressive intraoral and extraoral herpetic lesions. The successful treatment of HSV infections is complicated by the increasing prevalence of drug resistant mutants, which is becoming a clinical problem, especially in immunocompromised individuals. This possesses the need for new antiviral drugs and alternate therapeutic strategies against mutant viruses. An understanding of the mechanisms by which DNA is replicated and mutations evolve will be of value for future designs of new antiviral drugs and treatments. DNA polymerase (pol) is the pivotal enzyme involved in DNA replication. It plays the central role controlling the mutation rate by two major steps: selection of the correct nucleotides to be incorporated into the growing primer terminus, and proofreading or editing of the incorrectly incorporated nucleotides. Numerous mutagenesis and kinetic studies of a variety of Pols have already been conducted in vitro to reveal the mechanisms controlling the fidelity of DNA replication. HSV DNA replication has been proven to be an excellent model for the study of DNA replication, since HSV can be genetically amended for in vivo and in vitro characterization. Using this unique property, the effects of mutations in the pol gene can be analyzed in virus-infected mammalian cells. The in vitro characterizations of the same mutant Pol can also be studied by molecular biological and biochemical assays. Therefore, information obtained from the studies of a variety of mutant pols will be of value for a better understanding of the molecular
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mechanisms of DNA replication and replication fidelity. This information will also shed light on the structure-function relationship of Pol, which will be useful for future studies of new antiviral treatments. Our goals in this project include the following: 1. To examine the mutation spectra in different target genes induced by various HSV pols. 2. To examine sequence context effects on the misinsertion fidelity of HSV pols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FORMULATION OF COMBINATION MICROBICIDES Principal Investigator & Institution: Rohan, Lisa C.; Magee-Womens Hlth Corp Pittsburgh, Pa Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Description (provided by applicant): The overall goal of this proposal is to develop a formulated combination microbicide which will prevent the spread of human immunodeficiency virus (HIV) both vaginally and rectally utilizing multiple protective factors which inactivate the virus at different stages in its replication cycle. Inhibition of HIV attachment to the CD4 cellular receptor will be accomplished by formulating plantderived flavonoids with sulfated polysaccharides (carrageenans). There will therefore be redundancy built into the microbicide to inhibit HIV binding to its cellular receptor. Virucidal compounds, which destroy the viral envelope, will also provide redundant protection from infection. Both the antiviral ether lipid 1-0-octylsn- glycerol and citric acid will destabilize the envelopes of viral particles. Furthermore, the HIV reverse transcriptase will be inactivated by both antiviral flavonoids and a non-nucleoside reverse transcriptase inhibitor (Dr. Parniak, Project 1). Herpes simplex virus (HSV) will also be targeted by flavonoids, carrageenans, 1-0-octyl-sn-glycerol and citric acid to reduce genital ulceration and consequently the transmission of HIV to a greater extent than inactivating HIV only. Methods will be developed to quantify antiviral agents at each step in the pre-formulation and formulation process and physical and chemical pre-formulation data including solubility, stability, partitioning, and permeability data will be developed as part of these studies. Once active agents have been selected, their compatibility and toxicity with normal vaginal microflora and local tissues in both the isolated and formulated state will be determined. Following the initial formulation and development of a combination microbicide product, the microbicide will be optimized to maximize each antiviral mechanism and minimize toxicity in an iterative manner. The final formulated product will undergo stability testing, and product assessments will be made to ensure that the product has appropriate physical, chemical, microbiological, and antiviral properties during its shelf life. This project contributes to the program by producing new combinations of formulated microbicides based upon inhibition of viral replication using multiple and redundant antiviral mechanisms. Formulated combination microbicides produced in this project will be evaluated in vitro against HIV (Dr. Parniak, Project 1; Dr. Gupta, Project 2) and normal vaginal flora (Microbiology Core, Dr. Hillier), and as well as in humans (Dr. Landers, Project 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE ENGINEERING OF NERVE STEM USING HSV AMPLICON VECTOR Principal Investigator & Institution: Saeki, Yoshinaga; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004
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Summary: (provided by applicant): The development of a novel strategy to genetically modify neural stem/progenitor cells (NSCs) both in vitro and in vivo will have a significant impact on the development of NSCs-mediated cell therapy for neurological disorders as well as on the advance of basic developmental neurobiology. We recently have developed a packaging system for herpes simplex virus (HSV)-based amplicon vectors free from helper virus contamination or viral gene expression. Using this technology, we have demonstrated that genomic DNA inserts over 100 kilobases can be packaged into HSV virions, delivered intact, and expressed in cultured cells in vitro. By adding Epstein-Barr virus (EBV)-based replicon elements, HSV amplicons with genomic DNA inserts (HSV/EBV/genomic vectors) were shown to replicate and be maintained as extra chromosomal elements in infected cells, and express functional gene products for a long period of time. The unique properties of this vector system lead us to hypothesize that HSV/EBV/genomic vectors can be a platform technology to achieve some of the long-term goals toward the development of NSCs-mediated cell therapy, namely: 1) Complementing genetic defects of diseased NSCs in vitro and in vivo to treat genetic neurological disorders, 2) stable and cell type-specific transgene expression in neurons and glial cells differentiated from the transduced NSCs, and 3) genetic engineering of NSCs for controlled proliferation, migration, and differentiation in vivo after transplantation. To evaluate the feasibility of this approach, this project proposes to: 1) Verify episomal replication and maintenance of HSV/EBV/genomic vectors and evaluate furictional transgene expression from the vectors in dividing NSCs in culture, and 2) verify stable and cell-type-specific expression of genomic transgenes in terminally differentiated neurons and glial cells both in vitro and in vivo. We will examine five human genes, hypoxanthine-phosphoribosyltransferase, nestin, myelin basic protein, glial fibrillary acidic protein, and microtubule-associated protein tau as a housekeeping, NSC-specific, oligodendrocyte-specific, astrocyte-specific, and neuronspecific gene, respectively. These studies will provide further understanding of HSV/EBV/genomic vectors and confirm the advantages of genomic transgenes and EBV elements, which then should provide a strong basis for genetic engineering of NSCs using HSV/EBV/genomic vectors Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR GLIOMA Principal Investigator & Institution: Lowenstein, Pedro R.; Director and Professor; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Glioblastoma multiforme (GBM) is the most aggressive brain tumor and kills through intracranial growth and spread. We have previously shown (i) the efficiency of the herpes simplex virus type 1 thymidine kinase (HSV1-TK) and systemic ganciclovir (GCV) in eradicating an experimental syngeneic glioma model, (ii) 2-3 fold higher astrocyte- and glioma-specific high-level expression from the powerful 1.4kb major immediate early routine cytomegalovirus promoter (mCMV) compared to the human CMV equivalent, and (iii) unexpected long-term presence (12 months) of HSV1-TK in the brain. Although the efficiency of HSV 1-TK and GCV has been shown in a large variety of experimental models, the clinical results, while encouraging, remain inconclusive. The main reason thought to underlie this difference is the low levels of HSV1-TK expression from currently available vectors. Our experiments will address this issue by vastly increasing therapeutic transgene expression (through the use of a novel promoter) and reducing the viral vector toxicity (through the use of novel safer vectors of reduced toxicity). These findings will have
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important clinical implications and provide a blueprint for the implementation and design of Phase I clinical trials of gene therapy for GBM. We will validate the efficiency of a novel, safe, high capacity, helper dependent adenoviral vector (HC-Ad) expressing HSV1-TK under the control of the powerful mCMV promoter in a clinically relevant syngeneic experimental glioma model. HSV1-TK induces glioma cell death by phosphorylating the prodrug GCV, and killing both transduced and adjacent nontransduced, actively dividing cells. Killing of non-transduced cells, the 'bystander effect', amplifies this strategy's efficiency through cell-cell diffusion of cytotoxic intermediates (e.g. phosphorylated GCV), release of pro-apoptotic molecules, and immune stimulation. We hypothesize that our novel anti-tumor strategy will deliver high intraand peritumoral expression of the therapeutic transgene that, combined with systemic dosing of GCV, will lead to sustained and effective anti-tumor effect. Our long term aim is to translate this novel therapeutic approach into a Phase I clinical trial for GBM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR HEREDITARY TUMORS IN MODELS OF NF2 % TSC Principal Investigator & Institution: Breakefield, Xandra O.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 23-JAN-1987; Project End 31-AUG-2006 Summary: (provided by applicant): Studies will be undertaken to develop modes of gene delivery to experimental neural tumors for therapeutic intervention. Neoplastic lesions associated with tuberous sclerosis (TSC) including subependymal glial nodules, giant cell astrocytomas and cortical hamartomas, are believed to represent the consequences of loss of tumor suppressor genes on growth of astrocytes, neuroprogenitor cells and mesenchymal elements. Tumor models in the TSC2 heterozygous and conditional knock-out mice have been chosen as they are genotypically similar to mutations seen in patient cells and derive spontaneously from endogenous cells. They include liver hemangiomas, renal cell carcinomas, cortical hamartomas, and potentially subependymal glial nodules. Gene delivery to these tumor cells will be explored using three types of hybrid amplicon vectors derived from herpes simplex virus type 1 (HSV): one bearing a tetracycline (tet)-regulatable transgene cassette; one bearing elements of adeno-associated virus (AAV) to promote chromosomal integration; and one with both Epstein Barr virus (EBV), elements to promote episomal retention, and retrovirus vector elements (RV), to convert ampliconinfected cells into retrovirus producer cells. Vectors will be delivered through the intravascular route, either directly or via endothelial carrier cells to vascularized tumor foci; by intrathecal injection for brain lesions; and by direct intratumoral injection to large tumor masses. The efficiency and longevity of gene delivery to tumors in vivo will be established using reporter genes. Effective delivery modalities will incorporate therapeutic transgenes for anti-angiogenic and apoptosis factors, and consequences to tumor growth and pathology will be evaluated. In parallel, we will incorporate additional elements into these vector systems to increase the fidelity of regulatable transgene expression and to facilitate gene delivery to slowly growing tumors, typically seen in patients. This will include, in the first case, use of a tetracycline-silencer element and elimination of the VP16 transactivating protein from virions to achieve a "full off? state in the absence of drug, and, in the second case, replacement of RV elements in the HSV/EBV vector with components of lentivirus (LV) vectors, which are able to integrate transgenes into both dividing and non-dividing cells. TSC2 +/-transgenic and TSC1 conditional knock-out animals will be provided by Dr. Kwiatkowski (Project 12);
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pathologic expertise by Dr. Louis (Core C); assistance with vector engineering by Dr. Sena-Esteves; and MRI analysis by Dr. Weissleder. This project is designed to develop a strategy for reducing bulk in slow growing, benign tumors using vectors safe enough for eventual human use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY, STRESS AND HIPPOCAMPAL FUNCTION Principal Investigator & Institution: Sapolsky, Robert M.; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The hippocampus has been studied for its synaptic plasticity, role in cognition, and the neurogenesis that occurs in the adult hippocampus. With this has come an appreciation of endocrine modulators of hippocampal function. Specifically, glucocorticoids (GCs), adrenal steroids secreted during stress, disrupt [or] impair facets of synaptic plasticity and cognition, and inhibit neurogenesis. Estrogen, in contrast, enhances plasticity, cognition and neurogenesis. There has also been progress in the use of viral vectors to deliver transgenes into the CNS. We will use herpes simplex virus-1 vectors in a gene therapy strategy to protect the hippocampus from the disruptive effects of GCs and of stress, and to divert some of those GC effects into salutary estrogenic ones. We have constructed and wish to explore the protective potential of vectors expressing a) an enzyme which degrades GCs; b) a dominant negative GC receptor; c) a chimeric steroid receptor which binds GCs but has the genomic actions of an estrogen receptor. In Aim 1, we will alter these vectors to make them inducible by stress and GCs, as a means to have their expression triggered by insults. We will then characterize their patterns of expression. We will then examine the protective potential of these vectors, examining if the first two spare neurons from adverse GC effects, and if the chimeric vector also generates the salutary estrogenic effects when exposed to GCs. In Aim 2, the endpoint will be long-term potentiation in hippocampal slices generated from rats with differing pre-mortem regimes of GC exposure or stress. In Aim 3, we will study the effects of GCs, stress, and these vectors upon a hippocampal-dependent cognitive task. In Aim 4, we will study neurogenesis in vitro and in the adult hippocampus. We will characterize the effects of GCs, stress and estrogen upon it. We will then determine whether these vectors can protect neurogenesis from the inhibitory effects of GCs and, in the case of the chimeric vector, harness this to produce stimulatory estrogenic effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE TRANSFER FOR PREVENTION OF DIABETIC NEUROPATHY Principal Investigator & Institution: Fink, David J.; Professor; Neurology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2006 Summary: (provided by applicant): Polyneuropathy is a common and often debilitating complication of diabetes. In several animal models of diabetic neuropathy, it has been demonstrated that trophic factors administered by systemic injection may prevent progression or reverse signs of neuropathy. But translation of systemic trophic factor therapy to human disease has not succeeded, in large part because patients have proven to be unable or unwilling to tolerate the range of doses that are required to achieve a therapeutic effect. We have engineered and developed recombinant replicationincompetent genomic herpes simplex virus (HSV)-based vectors for gene transfer to the
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nervous system, and in the initial grant proposed to exploit the natural tropism of these vectors for peripheral sensory neurons of the dorsal root ganglion (DRG) to test the hypothesis that neurotrophin gene transfer to the DRG by means of an HSV-based vector can be prevent the progression of diabetic neuropathy. We now propose to extend these studies to accomplish two groups of specific aims, designed to explore the most effective strategy for the development of a novel therapy for diabetic neuropathy and to explore the molecular basis of that effect. Specific Aim 1. To define the time course of protection against diabetic neuropathy comparing transiently active promoter with a promoter that provides prolonged transgene expression. Specific Aim 2. To determine the dose-response characteristics of the vector-mediated effect. Specific Aim 3. To determine whether HSV-mediates gene transfer of IGF-1 or VEGF165 alone or in combination with NGF, is effective in preventing the progression of diabetic neuropathy. Specific Aim 4. To examine the effect of STZ diabetes on the alteration in gene expression in DR (neurons and Schwann cells in vivo, and to identify specific alterations in that expression that are reversed by vector transduction. Specific Aim 5. To construct a vector with a regulatable "switch" to control transgene expression safe). Diabetic neuropathy is a difficult complication of the primary disease. Factors of known therapeutic efficacy have been identified in animals models, and we have made substantial progress in constructing a vector to deliver these factors to the peripheral nervous system. The studies in this proposal are designed to allow the development of an effective therapy appropriate for the treatment of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENERATION OF HERPES VIRUSES FOR IN VIVO OBSERVATION Principal Investigator & Institution: Maul, Gerd G.; Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The effect of viruses on the host can be observed at different levels of complexity and resolution depending on the technique used. The single-cell observation combined with various labeling techniques has provided great insight into host-virus interactions; however, the observations are made on fixed (dead) infected cells. We propose to develop an in vivo virus genome labeling system that will allow observation of virus genomes in live cells. Visualization of a viral genome in vivo requires tagging its DNA sequence. The construction of a "green" genome is possible by labeling a DNA tag in the viral genome as it enters the nucleus or before packaging with green fluorescent protein (GFP). Cells inducibly producing the GFP-fusion protein to bind to the DNA tag will be generated to assemble a system where upon virus entry into the nucleus or during packaging the viral genome is rendered "green" through very tight binding of the DNA tag and the reporter protein. These genomes can be visualized by confocal microscopy and documented in a time-resolved fashion by time-lapse microscopy. We propose to produce DNA-tagged recombinant herpes simplex virus and mouse cytomegalovirus. To complete the system, we will develop cell lines that inducibly produce GFP-labeled DNA-binding protein, where HSV-1 and MCMV can replicate and which are useful as quiescent ("latent") virus containing cultured cell model systems. Such a new system would recognize single viral genomes directly in the live cells and obviate in situ hybridization. The "green" viral genomes will open up new lines of inquiry into the dynamics of virus entry into the nucleus, the sequence of degradation by endonucleases and/or retention in a nuclease-resistant episome, replication and segregation by multiple observation of single cells or populations during
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quiescence, affinity immune separation of quiescent viral genomes and identification of viral genomes by immunoelectron microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICALLY ENGINEERED VIRUSES FOR BRAIN TUMOR THERAPY Principal Investigator & Institution: Martuza, Robert L.; Chief of Neurosurgery; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAY-1994; Project End 31-MAR-2007 Summary: (provided by applicant): We have developed genetically engineered herpes simplex virus-1 (HSV-1) vectors that can selectively and efficiently infect and kill brain tumor cells in situ without harming surrounding brain cells and without causing systemic disease. Having taken one such vector into human clinical trial, we set forth testable hypotheses aimed at further understanding and improving this method of brain tumor therapy. In order to increase the efficacy of HSV oncolysis in brain tumor therapy, we hypothesize that: a.) HSV oncolytic therapy can be improved by using a HSV vector in conjunction with commonly used chemotherapeutic agents for brain tumors; b.) The efficacy of herpes vectors for brain tumor therapy can be improved through the use of a HSV backbone that replicates better in glioma cells while retaining the necessary safety features for clinical trials. In order to better understand and improve the delivery of HSV vectors for brain tumor therapy, we hypothesize that: a.) Some of the efficacy following intravascular or intratumoral HSV tumor therapy may be due to selective injury of tumor vasculature versus normal vasculature; b.) The timing of co-treatment with antiangiogenesis agents may either inhibit or augment the selective injury to tumor vasculature by oncolytic HSV vectors; c.) Prior anti-HSV immunity could alter the efficacy of intravascular delivery of oncolytic HSV but can be modulated with immunosuppressive agents. In order to further improve the anti-tumor immunity induced by HSV tumor therapy, we hypothesize that: a.) Defective HSV vectors expressing immune-modulatory genes will increase the survival of animals harboring intracranial tumors, b.) A recombinant virus can be constructed from an appropriate parent virus that will express a cytokine without down-regulating MHC-I thus enhancing the anti-tumor immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HERPES SIMPLEX VIRUS AND NGF DIFFERENTIATED PC12 CELL INTERACTION Principal Investigator & Institution: Block, Timothy M.; Professor and Director; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 31-AUG-2006 Summary: Description (provided by applicant) This project is concerned with how neuronal cells manage HSV infection at the intracellular level. The intracellular details of HSV/neuronal cell interactions are difficult to study in vivo. Information regarding the mechanisms and kinetics of HSV genome physical organization following neuronal cell infection in vivo and even in vitro is extremely limited. We have, therefore, developed a tissue culture system of quiescent HSV infection using nerve growth factor (NGF) differentiated cells. This system will be used to determine the impact of HSV upon NGF differentiated cells and to track the fate and structure of viral DNA following infection. Briefly, NGF differentiated PC 12 cells have been shown to support long-term "quiescent" infections of HSV-1. NGF differentiated PC12 cells are not killed by virus
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infection and, surprisingly, persist longer than uninfected controls. There is little viral transcription and progeny is not detected in the culture medium, despite the presence of an inducible infectious genome. Strangely, the viral genome in quiescently infected PC12 cells persists as a linear form for several weeks before ultimately assuming an endless, presumably circular, state. These cells will, therefore, be used to study (a) if and how HSV can cause populations of PC12 cells to have a survival advantage over uninfected populations; (b) how linear viral genomes can be maintained intact, for weeks in neuronal like cells; (c) the mechanism(s) involved in their assumption of an endless, possibly modified, quiescent viral genomic state. Observations made in this in vitro system will be related to in vivo mouse models of latency by comparing the physical properties of viral DNA derived from tissue derived from infected mice with that from quiescently infected PC12 cells. This work will thus allow for the testing of hypotheses made about HSV latency seen in the vitro system, in mouse models of latency. Some of the information being uncovered in the in vitro, quiescent infection system has the exciting potential to influence our understanding of how HSV genomes are organized and "silenced". Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HERPES SIMPLEX VIRUS IN THE TREATMENT OF ORAL CANCER Principal Investigator & Institution: Shillitoe, Edward J.; Professor and Chairman; Microbiology and Immunology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: We will develop new strains of Herpes simplex virus type-1 (HSV- 1) for use in the treatment of oral cancer. HSV- 1 has potential as a therapeutic tool for oral cancer since it infects oral epithelium as its natural host tissue, is highly cytotoxic, and spreads rapidly from one cell to another. The only disadvantage of HSV-1 is that it can spread to the nervous system, causing paralysis and death. To prevent this, we will develop a new strain of the virus whose replication is limited to oral cancer cells. This will be done by removing a promoter that controls expression of an essential viral gene, and replacing it with a promoter that is active in oral cancer cells but not in nervous- system cells. We will increase the anti-tumor effect of the virus by adding a gene for a cytokine. This will increase the local immune response to the infected tumor. We will then make the antitumor effect even stronger by exploiting the anti-tumor bystander effect that occurs when ganciclovir is activated by HSV-1. We expect that the triple combination of a tumor- restricted virus, enhanced local immune response, and anti-tumor bystander effect will be more effective in treatment of an experimental model of oral cancer than other treatments, and could lead to human trials in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HERPES SIMPLEX VIRUS INHIBITION OF CTL INDUCED APOPTOSIS Principal Investigator & Institution: Jerome, Keith R.; Laboratory Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2001 Summary: The herpes simplex viruses (HSV) establish lifelong infection in their host. These viruses are thought to have evolved in parallel with their hosts, and therefore have developed intricate strategies for co-existing with the immune response. In preliminary studies for this proposal, I have demonstrated that HSV-1 inhibits the
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oligonucleosomal DNA fragmentation characteristic of apoptosis, including apoptosis induced by CTL. Since recent reports suggest that cells undergoing apoptosis are not suitable for viral replication, the induction of apoptosis may be a critical function for CTL control of viral infection. Inhibition of apoptosis would therefore promote viral replication. In contrast to its inhibition of DNA fragmentation, HSV has no effect on the membrane manifestations of apoptosis, such as phosphatidylserine exposure. In this proposal, the ability of HSV-2 to inhibit apoptosis will be evaluated. The HSV-1 and -2 genes mediating the anti-apoptotic effect will be identified, using compounds limiting HSV gene expression to individual transcriptional classes, followed by analysis of HSV deletion mutants. The cellular targets of each HSV anti-apoptotic gene will be identified using the yeast two-hybrid system. Finally, the ability of HSV to interfere with different apoptosis-inducing mechanisms of CTL will be determined using anti-Fas antibody and isolated perforin and cytotoxic granule components. The results of these studies will improve our understanding of HSV evasion of the immune response, and may suggest therapeutic strategies to circumvent this evasion. In addition, these studies will provide new probes and insight into the cascade of intracellular events following induction of apoptosis, especially the terminal effector events, since HSV inhibits nuclear but not membrane events of apoptosis. The work will also provide insights into how the manifestations of apoptosis vary depending on the inducing stimulus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HERPES SIMPLEX VIRUS TERMINASES Principal Investigator & Institution: Baines, Joel D.; Associate Professor; Microbiology and Immunology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-DEC-2003 Summary: The long term goal of these studies is to elucidate the molecular mechanisms by which herpes simplex virus cleaves intranuclear concatameric viral DNA and packages the DNA into preformed intranuclear capsids. We and others have found that several proteins including UL6, UL15, UL17, and UL28 proteins are essential for DNA packaging but are dispensable for assembly of capsids. We hypothesize that procapsids (bearing UL6 in the outer shell and UL28 in the inner shell) are transported by action of UL17 protein to intranuclear sites containing the ATPase- bearing terminase subunit UL15. UL15 (bound indirectly to DNA) docks with UL6 protein in the capsid and is proteolytically cleaved. The cleaved protein binds the procapsid-bound DNA- binding subunit of the terminase, UL28 protein. The two subunit terminase then cleaves DNA that is looped into the capsid, scans DNA for a second cleavage site, and exits the capsid after this second cleavage. The goals of specific aims in this proposal are to test predictions of this hypothesis. Specific aim 1 will test the significance of UL15 proteolytic cleavage to cleavage and packaging, and test relevance of UL15 docking with capsid-bound UL6 protein. The pursuit of this aim will also include characterization of the UL15 docking site. Specific aim 2 will determine how UL28 associates with the capsid and test the relevance of detected DNA binding and cleavage activities of UL28 protein to DNA cleavage/packaging. The relevance and mechanism of interaction with UL15 protein will also be tested. The goals of specific aim 3 are to determine the role and mechanism of UL17 capsid/capsid protein transport in living cells and determine the relevance of this activity to cleavage/packaging. The relevance of the activities/interactions addressed in specific aims 1-3 will include identification of mutations that disrupt the activities/interactions in vitro, followed by testing proteins
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bearing such mutations for the ability to rescue viral null mutants lacking the respective proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HERPES SIMPLEX VIRUS, EARLY BRAIN INJURY AND EPILEPSY Principal Investigator & Institution: Eid, Tore; Neurosurgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Herpes simplex virus type 1 (HSV-1) is a common cause of acute and recurrent disease in humans. After the primary infection, which usually occurs in childhood, HSV-1 remains dormant in the nervous system. This proposal is aimed at exploring a novel hypothesis that early infection with HSV-1 plays a critical role in the genesis of temporal lobe epilepsy (TLE). The virus may contribute to this by creating a specialized brain focus involving alterations in neural circuitry and formation of a unique glial/microvascular substrate that promotes epileptogenesis and maintenance of seizures. Several observations suggest that HSV-1 may cause TLE. For example, survivors of HSV-1 encephalitis frequently develop epilepsy. HSV-1, when causing encephalitis, preferentially invades and lesions limbic structures, including the hippocampus, which also shows neuropathological changes in TLE. Moreover, patients with medically intractable TLE have a ten times higher rate of latent HSV-1 infection in their hippocampus than control subjects. To evaluate our hypothesis two approaches are proposed. (1) To critically explore the connection between HSV-1 and TLE by assessing the presence of viral DNA (by polymerase chain reaction) and virions (by immunohistochemistry) in surgically resected hippocampi from TLE patients, and correlating these with the specific neuropathological characteristics of TLE, i.e. (a) loss of hilar interneurons, (b) gliosis, and (c) vascular proliferation. (2) To assess the causal relationship of HSV-1 to the development of chronic seizures and neuropathology in TLE, rat models of HSV-1 infection will be studied and experimental modifiers of infection such as (a) viral strain, (b) age, (c) fever/febrile seizures, and (d) acute seizures, will be evaluated. The cellular/molecular mechanisms of viral-induced neuropathology and seizures will be explored by investigating the pattern and time-course of viral invasion during the infection. If a viral causation of TLE is established, then this would not only open new avenues for prevention and control of this disorder, but also improve our understanding of viral-induced brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HERPES SIMPLEX VIRUS-1 LAT PROMOTER ANALYSIS Principal Investigator & Institution: Garza, Hildegardo H.; Texas A&M UniversityKingsville 700 University Blvd Kingsville, Tx 78363 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: Recurrent herpes simplex virus type 1 (HSV-1) ocular infections are the leading infectious cause of blindness in industrialized nations. Fewer than 10% of clinical cases are primary acute infections; the remaining 90% are recurrences of latent HSV-1. Although HSV-1 can reactivate spontaneously, stress and trauma (e.g., hypoand hyperthermia, ultraviolet light irradiation, and ocular surgery) can also reactivate latent HSV-1. The latency-associated transcript (LAT) gene has been implicated as a component of the pathway that induces the conversion from latency to an acute infectious state. While the LAT gene is known to be the only gone that is abundantly transcribed during latency, it does not appear to code for any known protein.
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Furthermore, the LAT transcript that accumulates during latency is not the coding region, but is probably a stable 2.0 kb intron that is spliced out of the primary 8.5 kb LAT transcript. This proposal aims to dissect out the transcriptional control of the LAT promoter and its associated enhancer region from three distinct strains of HSV-1. These three strains of HSV-1 differ in their ability to undergo spontaneous and stress-induced reactivation. If the pathway by which the virus senses and responds to adrenergic stimuli can be established, it should prove to be a rich source of therapeutic targets. This is desirable since antiviral therapy merely delays the onset of blindness and viruses may become resistant to treatment. The specific aims that will address this issue are: 1) To assess the efficacy of the three LAT promoter regions in driving luciferase production in neuronal and fibroblast cell cultures, 2) To assess the effect of the three LAT enhancer regions on luciferase production in neuronal and fibroblast cell cultures, and 3) To assess the effect of different combinations of LAT promoters and enhancers on luciferase production in neuronal and fibroblast dell cultures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HERPESVIRUS PERSISTENCE AND ONCOGENICITY Principal Investigator & Institution: Shenk, Thomas E.; Professor & Howard Hughes Investigator; Molecular Biology; Princeton University 4 New South Building Princeton, Nj 085440036 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Changes in cellular biochemical pathways are fundamental to herpesvirus persistence and oncogenicity. We will employ new global approaches to identify viral genes that modulate cellular pathways and to identify the pathways that are altered, and then we will elucidate the mode of action of these altered pathways within the infected cell. Our approach will be comparative. The program will include the study of viruses in each of the three families of herpesviruses: alpha, herpes simplex type 1 virus and pseudorabies virus; beta, human cytomegalovirus; and gamma, Epstein- Barr virus and Kaposi sarcoma-associated herpes virus. Some herpes viruses contribute to human cancers (Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus), while others are not known to do so. Consequently, our program will compare tumor viruses with closely related non-tumor viruses. The long-term objective of the program is to better understand the mechanisms by which herpesviruses persist and contribute to oncogenesis in the infected host. We will search for additional viral genes that mediate persistence and oncogenicity, and we will study the mechanism of action of new genes that are identified. We also will identify cellular genes whose level of expression change after infection, and test the hypothesis that some of these altered cellular genes influence the outcome of the virus-host interaction, contributing to the persistence and/or oncogenicity of the viruses. The individual research projects are as follows. Project 1, Roizman. Comparative role of cellular functions in herpes simplex type 1 virus infection. Project 2, Enquist Comparative alpha-herpesvirus (herpes simplex type 1 virus and pseudorabies virus) infection of the nervous system. Project 3, Shenk: Viral and cell gene function in human cytomegalovirus replication and latency. Project 4, Moore: Viral and cellular gene regulation in Kaposi sarcoma-associated herpesvirus-associated tumors. Project 5, Kieff: Epstein-Barr virus and cell gene expression in latency and oncogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HETEROCONJUGATE VACCINES AGAINST HERPES SIMPLEX VIRUS Principal Investigator & Institution: Zimmerman, Daniel H.; Cel-Sci Corporation 8229 Boone Blvd, Ste 802 Vienna, Va 22182 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-AUG-2004 Summary: The primary goal of this program is the development of L.E.A.P.S.(TM) heteroconjugate peptide vaccines against herpes simplex virus) to prevent or treat human infection. The heteroconjugate vaccines are constructed of peptides which contain defined T cell epitopes and peptides which are predicted to bind to T cells or antigen presenting cells. The T cell epitopes that are being used are from the ICP27, glycoprotein B, and glycoprotein D of HSV-1. Our Phase I studies proved the principle behind this new technology by showing that incorporation of a viral peptide epitope into a L.E.A.P.S. construct based vaccine can enhance and define the type of immune response which is elicited to promote the development of protective and not detrimental immune responses. A L.E.A.P.S. vaccine can then be formulation with LEAPS constructs assembled with adjuvants to produce defined immune responses to defined epitopes. The major goal of the Phase II studies will be to optimize the vaccine formulation with respect to L.E.A.P.S. peptide (or mixture), the adjuvant and other components to allow progression to human trials. In addition, we will study the mechanism of action by which the L.E.A.P.S. peptide potentiates the immune response. The HSV vaccines are also prototypes for the development of heteroconjugate vaccine to treat or prevent disease caused by other infectious agents. The ultimate goal of our study will be to develop sufficient data to allow progression to human trials. PROPOSED COMMERCIAL APPLICATION: Heteroconjugate peptide vaccines use proprietary new technology called L.E.A.P.S. (Ligand Epitope Antigen Presentation System) to provide treatment and/or prophlysis against herpes simplex virus (HSV) infection and disease. HSV is a common oral pathogen and sexually transmitted disease which also causes serious disease. An estimated 40 to 60 million Americans are infected with HSV with approximately 600,000 new cases occurring per year. The HSV vaccine will be prototypes for the development of heteroconjugate vaccines to treat or prevent disease by other infectious agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH-TITER HELPER VIRUS-FREE HSV-1 VECTORS Principal Investigator & Institution: Geller, Alfred I.; Associate Professor of Neurology; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): HSV-1 vectors are attractive for gene therapy of aging disorders that affect the brain because HSV-1 can persist indefinitely in neurons in the latent state and large HSV-1 vectors can coexpress multiple genes. This laboratory has developed a Herpes Simplex Virus (HSV-1) plasmid vector system for gene transfer into neurons. Using this system, we have begun to explore gene therapy approaches to specific aging disorders that affect the brain, such as Parkinson's Disease (PD). We have shown that delivery of a HSV-1 vector that expresses human tyrosine hydroxylase into the partially denervated striatum in the 6-hydroxydopamine rat model of PD results in long-term (1 year) biochemical and behavioral correction. Other investigators have demonstrated the potential of using this vector system for gene therapy for a number of other neurological disorders. We developed a helper virus-free packaging system for
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these HSV-1 vectors. This improvement substantially reduces the cytopathic effects and the inflammatory response previously associated with gene transfer. Furthermore, we and others have recently identified specific promoters that support long-term expression in rat forebrain neurons. However, the relatively low titers remain one of the primary barriers to the use of this vector system for human gene therapy of aging disorders that affect the brain. The goal of this proposal is to develop a packaging cell line that can produce high-titer helper virus-free HSV-1 vector stocks. High-titer retrovirus, lentivirus, and adenovirus vector stocks have been produced using packaging cell lines, and these vector stocks have been used in human gene therapy. The first specific aim will isolate a cell line that stably maintains an HSV-1 genome that does not express any immediate early (IE) genes and lacks a packaging site. The second specific aim will produce high-titer, helper virus-free HSV-1 vector stocks by using an HSV-1 vector that contains the 3 essential IE genes flanked by lox sites. This packaging system is based upon standard genetic complementation. High-titer vector stocks will be produced by serial passaging. To excise the IE genes from the vector, the final passage will use a cell line that expresses Cre recombinase. The third specific aim will evaluate the safety features of this packaging system. The fourth specific aim will use these high-titer vector stocks to achieve gene transfer to large numbers of cells in the rat striatum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV RISK REDUCTION THROUGH HSV-2 PREVENTION WITH N-9 Principal Investigator & Institution: Padian, Nancy S.; Professor; Ob, Gyn and Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Viral sexually transmitted infections (STIs) are a significant health burden and in particular, women have limited options to protect themselves against them. Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) are two of the most prevalent viral STIs. Neither of these infections is curable, or preventable with available vaccines. Both have serious sequelae and implications for reproductive health. While HIV and HSV-2 infection have been demonstrated to be highly associated with each other, it has been postulated that infection with each virus may be a risk factor for infection with the other. Although both behavior change and the consistent use of condoms appear to protect against HIV, no prevention strategies for HSV-2 have been demonstrated to be effective. While this lack of effective prevention strategies may in part reflect the inadequacy of studies to date, the biology of HSV-2 -the fact that viral shedding occurs over a wide anatomic area in the genital region -suggests that condoms may be less effective for preventing transmission of HSV-2 than for preventing STIs associated with transmission through urethral and cervical secretions. Nonoxynol-9 appears effective in preventing HSV-2 infection in animal models, however, little is known about the effect of nonoxynol-9 in preventing HSV-2 infection in humans. This AIDS-FIRCA proposal is primarily aimed at determining if HSV-2 infection is an independent risk factor for HIV acquisition, and at defining the effect of intravaginal use of nonoxynol-9 in preventing HSV-2 acquisition. This proposal outlines a 3 year prospective cohort study of 1200 HIV uninfected women attending the Spilhaus family planning clinic in Harare, Zimbabwe. Baseline clinical, microbiologic, and laboratory data, including HIV and HSV-2 serologic tests will be obtained. If we establish that infection with HSV-2 increases susceptibility to HIV, and that nonoxynol-9 prevents transmission of HSV-2, we will have revealed a modifiable risk factor for HIV, as well as an inexpensive means of preventing HSV-2 infection and its attendant
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sequelae. By simply adding an additional tube of blood and a diagnostic test to an established phase III trial in Zimbabwe, the study being proposed here may answer these important questions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HSV AMPLICON VECTORS FOR HIV VACCINE DEVELOPMENT Principal Investigator & Institution: Dandekar, Satya W.; Professor & Chair; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (Provided by Applicant) The development of an effective prophylactic vaccine for HIV-1 will likely need an immunogen that can induce neutralizing antibody, and CD4 and CD8 T cell activity. Viral vector systems that infect cells and allow intracellular expression of HIV-1 gene products have the ability to activate T cells through MHC class I and II presentation. Herpes simplex virus type-1 (HSV-1) amplicons possess many of the desirable features of such a viral vector system. They are non-replicating, induce robust CD8+ T cell responses in mice, are easily manufactured, and infect a variety of antigen presenting cells, including dendritic cells. The HSV-1 amplicon can incorporate large segments of DNA, express more than one gene product, are not contaminated by helper virus, and are under development and evaluation as gene therapy tools. In initial experiments, HSV-1 amplicons expressing HIV-1 MN gp120 were shown capable of inducing interferon gamma-producing T cells at a number equivalent to that induced by live herpesvirus vectors, and far exceeding that of a modified vaccinia Ankara vector. In addition, the amplicons induced large anti-Env antibody responses. Building upon these observations, three specific aims are proposed. The first will be to construct amplicons which express codonoptimized clade C env, gag, and tat genes, and evaluate the protein expression from such vectors in vitro. In the second aim, the optimum route of parenteral and mucosal delivery, the dose and duration of immunity, and the effect of prior immunity to HSV will be evaluated. Lastly, the immune responses induced by the clade C amplicon will be evaluated in BALB/c and mapped in HLA-A2/human beta2 microglobulin transgenic mice. Overall, it is anticipated that these experiments will generate sufficient data to warrant moving the HSV-1 amplicon vaccine concept into non-human primate and human vaccine trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HSV US11 MEDIATED EVASION OF HOST SHUTOFF Principal Investigator & Institution: Cassady, Kevin A.; Pediatrics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: The Mentored Clinical Scientist Development Award will provide the opportunity to extend the applicant's intensive molecular virology training and develop an expertise in protein biochemistry and cellular biology. These skills will enable the applicant to become a fully independent research scientist and to address studies that dissect the molecular and genetic basis of viral infection and human disease. The mentor who will direct this training is an expert in herpes simplex virology. The candidate's career objective is to become a pediatrician- scientist who provides insights into viral pathogenesis which ultimately will improve the therapeutic and management decisions for patients with viral infections. Research interests of the applicant focus on the molecular and genetic basis for viral pathogenesis: specifically, how viruses evade
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intrinsic and immune host defense systems. This proposal examines how second-site mutations in avirulent herpesviruses enable progeny to reacquire their pathogenic potential and evade an intracellular host defense system, the interferon induced protein kinase (PKR). Studies have identified that a change in the kinetic expression of an HSV gene flanking the second site mutations (US11) contributes to the renewed pathogenicity of these viruses. These studies have not resolved a significant paradox: the early synthesis of US11 protein enables viral evasion of PKR but pre-made protein carried in with the virus is ineffective. The working hypothesis of this proposal is that while these functional differences in PKR inhibition may reflect inherent biochemical differences between the pre-made and synthesized US11, it is more likely that this reflects the relative ability of synthesized US11 to recruit accessory infected cell proteins. Biochemical techniques (chromatography, 2-D electrophoresis, in vivo phosphorylation) will be used to isolate and analyze virion-associated and synthesized US11. This will be followed by tests for functional differences using a PKR in vitro kinase assay. Affinity studies using both biochemical (immunoprecipitation, protein affinity) and genetic methods (yeast two hybrid system) will evaluate if US11 or PKR recruit participating infected cell proteins that modify the PKR pathway. An in vitro PKR kinase assay will test the functional significance of the identified proteins. Finally, biologic function will be evaluated by creating a cell line expressing the US11 and identified gene with an avirulent virus and examining for phenotypic changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN EXPLANT CULTURES AND A MOUSE TO EVALUATE SAMMA Principal Investigator & Institution: Cara, Andrea; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 26-SEP-2001; Project End 31-JUL-2005 Description (provided by applicant): Approximately 90% of new human immunodeficiency virus (HIV) infections are acquired through sexual contact. The development of safe, effective, and affordable topical microbicides for vaginal or rectal use could play a critical role in reducing HIV transmission rates worldwide. Clinical, epidemiological and molecular studies strongly support the role of herpes simplex virus (HSV) as a major cofactor for the transmission of HIV. Genital ulcers lead to breaks in the epithelial barrier and HSV induces the expression of pro-inflammatory cytokines that are known to enhance HIV replication. The goal of the proposed studies is to characterize the effects of sodium dimandelic acid ether (SAMMA) and its leading derivatives on HIV and HSV infection utilizing relevant biologic culture systems. SAMMA has excellent anti-mV and anti-HSV activity, while exhibiting no cytotoxicity in cell culture. While cell cultures may provide important information for the evaluation of microbicides, they may not adequately simulate events that occur in vivo. Human explant cultures (endocervical, ectocerivcal, vaginal and rectal), biologic fluids (cervicovaginal secretions and semen) and a mouse genital herpes model will be used in this Project to assess anatomic, physiologic, and immunologic factors that might impact on the activity of this novel class of compounds. Building on the in vitro cell culture data of Projects I, II and IV, the applicant will study the most active derivatives/isomers of SAMMA using biologic culture systems. In Aim 1, the most active derivatives will be evaluated for efficacy against HIV-1 infection of primary macrophages using human genital tract fluids and mucosal explant cultures. In Aim 2, mucosal explant cultures and a mouse model will be used to determine the efficacy of SAMMA to block HSV infection of epithelial cells. Inflammatory cells and cytokines will be measured to study the effects
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Herpes Simplex
of SAMMA on the innate immune system (Aims 1,2 and 3). The interrelationship between HIV and HSV and the efficacy of SAMMA to inhibit dual infection will be studied in Aim 3. Efficacy and safety data in relevant biologic culture systems may provide compelling support for advancing SAMMA or one of its derivatives to clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN RESISTANCE TO HERPES SIMPLEX VIRUS INFECTIONS Principal Investigator & Institution: Posavad, Christine M.; Associate Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Herpes simplex virus type 2 (HSV-2) is the major cause of genital herpes, one of the most frequent sexually transmitted diseases. The worldwide prevalence of genital HSV-2 continues to increase and the limited success of HSV-2 glycoprotein subunit vaccines underscores the urgency of defining innate resistance and protective immune responses to HSV-2 in humans. Because of the high seropositivity rate of HSV throughout the world, evidence of innate or acquired resistance to HSV was not previously suspected, We have, however, in the last year identified a group of individuals who are seronegative to HSV by repeated analyses using the most sensitive serologic assays but who possess CD4+ and CD8+ T cell responses to HSV at multiple time points over the course of prospective follow-up. Preliminary study revealed no evidence of HSV infection in these subjects. The goal of this proposal is to determine whether HSV-seronegative subjects who are chronically exposed to HSV-2 from infected partners exhibit acquired and innate mechanisms of resistance to HSV infection. These subjects are classified as immune seronegative, IS, if they possess HSV-specific T cell responses or as exposed-seronegative, ES, if they do not possess HSV-specific T cell responses. Specific Aim #I will identify IS subjects from HSV-2 discordant couples and evaluate if HSV-specific T cell responses differ qualitatively or quantitatively from those observed in HSV-infected persons with frequently reactivating genital herpes. We will characterize systemic and local T cell responses to HSV using standard chromium release assays, Elispot, intracellular cytokine staining and tetramer analysis. We will also determine if local antibody responses develop in ES and IS subjects. Specific Aim #2 will determine if polymorphisms exist in 3 HSV entry receptor genes, HVEM, nectin-1, and nectin-2 to evaluate whether one mechanism of resistance to HSV-2 infection could be analogous to the receptor mutations detected in some HIV-1-resistant persons. All 3 genes will be sequenced from ES and IS subjects and relevant HSV-2 infected subjects. If coding polymorphisms are present, we will determine whether these changes alter the efficiency of viral entry. Specific Aim #3 will explore a role for CD8-derived chemokines, MIP-lalpha, MIP-1beta and RANTES, in resistance to HSV infection. Preliminary data suggest that these chemokines are secreted at higher levels in IS subjects compared to non-IS subjects and further, that MIP-la inhibits HSV infection. We will determine if Beta-chemokines inhibit the binding of HSV to cell surface glycosaminoglycans, which binding is know to facilitate HSV entry. The results of these studies will improve our understanding of effective immune defense against HSV-2 infection and may identify a mechanism of genetic resistance to HSV. The data generated will be relevant to designing and evaluating strategies for HSV-2 preventative vaccines and immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IDENTIFICATION OF NOVEL ANTIVIRAL TARGETS USING RNAI Principal Investigator & Institution: Pachuk, Catherine J.; Nucleonics, Inc. 26 Spring Mill Dr Malvern, Pa 19355 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2004 Summary: (provided by applicant): The goal of this project is to develop a selection strategy using RNA interference (RNAi) to identify novel therapeutic targets for the treatment of cytolytic virus infection. RNAi is a cellular process that causes targeted elimination (silencing) of mRNA. Nucleonics, Inc. has developed platform technologies to exploit RNAi for development of therapeutics and genomic applications. These technologies provide powerful new tools for targeted elimination of specific mRNAs. RNAi will be used to selectively silence genes required for cytolytic virus replication thereby producing cells that will be resistant to infection. Repeated rounds of selection (infection with cytolytic virus) and enrichment (isolation of RNAi-inducing sequences in surviving cells) will identify genes that are potential therapeutic targets for treatment of virus infection. Phase I of this application focuses on ( i ) optimizing vectors and delivery systems for inducing RNAi in mammalian cells and (ii) "proof-of-concept" tests using these vectors and delivery systems to silence viral and cellular genes known to be required for cytolytic virus replication. Two cytolytic viruses will be tested in this system, a DNA containing virus, human herpes simplex virus type I (HSV-1), and an RNA containing virus, bovine viral diarrhea virus (BVDV). BVDV is a tissue culture surrogate for hepatitis C virus. Phase II of this proposal focuses on using this selection to identify novel genes required for cytolytic virus infection and validate these novel targets in cell culture and animal models of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IL-6 IN HERPES SIMPLEX VIRUS TYPE 1 OCULAR REACTIVATION Principal Investigator & Institution: Kriesel, John D.; Associate Professor; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: There are approximately 50,000 cases of new or recurrent ocular HSV disease per year in the U.S., with stromal scarring of the cornea leading to reduced visual acuity in about 6,000 patients per year. Acute and recurrent herpes simplex keratitis are leading indications for corneal transplantation in this country. Ultraviolet light (UV) exposure, fever, hyperthermia, hypothermia, dental trauma and surgical manipulation of the trigeminal ganglion are stimuli associated with reactivation of HSV-1. The sequence of HSV gene activation during productive infection is well known, but the mechanism by which reactivation stimuli, including UV light, stimulate latent virus to replicate is unknown. Studies by the principal investigator have shed new light on this mysterious process, implicating the inflammatory cytokine interleukin-6 (IL-6) and its associated cellular transcription factor STAT3 in the pathogenesis of ocular HSV reactivation. New supporting data presented in this application demonstrates that ocular UV exposure induces IL-6 production in explanted corneas. By contrast, the same UV stimulus induces and activates the transcription factor STAT3 in the trigeminal ganglion, the site of the latent viral infection, where this factor is hypothesized to initiate HSV-1 gene transcription. This specific aims of this proposal are to: 1)Investigate the role of IL-6 in the murine keratitis model by: a) directly injecting IL-6 into the conjunctiva of latently infected mice and b) studying the ability of IL-6 knockout mice to reactivate HSV-1. 2)Explore the hypothesized IL-6STAT mechanism of induced HSV ocular reactivation. Based on supporting data, studies are proposed: a) to detect
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Herpes Simplex
activated, phosporylated STAT transcription factors and b) determine whether these factors specifically bind important HSV-1 genes. 3)Directly investigate the hypothesis that IL-6 drives HSV-1 gene transcription. A collaborative effort is outlined to study this using HSV-1 transient expression and/or reporter construct assays. Novel and specific viral mutants will be constructed based on the results of HSV-DNA binding and transient expression assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMAGING TRANSGENE EXPRESSION IN GENE THERAPY PROTOCOLS Principal Investigator & Institution: Blasberg, Ronald G.; Professor; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-JUL-2002; Project End 31-MAR-2006 Summary: (Applicant's Description) We propose to assess transgene expression by noninvasive imaging in patients undergoing gene therapy. Four separate components, involving four different clinical trials, are included in this proposal in order to provide a broad clinical spectrum for assessing the benefits and limitations of imaging transgene expression in a clinical setting. Three different viral vectors (adenovirus, Herpes Simplex Virus, and retrovirus) will be used in these clinical trials and this will provide the opportunity to obtain comparable imaging data for each of the three vectors. Two of the components will involve patients in existing clinical trials at Mount Sinai Medical School in New York. One clinical trial involves patients with hepatic metastases from colorectal cancer, and the other involves patients with local prostate cancer; both trials involve direct intratumoral injection of an adenoviral vector (ADV-tk) expressing the Herpes Simplex Virus thymidine kinase gene (HSV1-tk), followed by intravenous ganciclovir treatment. The third and fourth components will involve both preclinical and clinical imaging studies at MSKCC, and will also involve patients with colorectal hepatic metastases. The third component involves an experimental treatment protocol where a replication restricted Herpes Simple Virus type-1 (mHSV1; G207 or R7020) is injected into the hepatic artery to induce selective cytolysis of dividing tumor cells (hepatic metastases). The fourth component will involve hepatic artery injection of a retrovirus (DCSV or SFG) containing a fusion gene which includes dihydrofolate reductase (DHFR) and HSV1-tk cDNA. The treatment rationale is based on data showing that exposure of transduced tumor cells to trimethotrexate (TMTX) will lead to amplification of DHFR and consequently, to amplification of the HSV1-TK as well; in turn, this will make the transduced cells more sensitive to ganciclovir. HSV-TK imaging will be performed using positron emission tomography (PET) and 124-I labeled FIAU (2'-fluoro-1-beta-D-arabinofuranosyl-5-iodo-uracil); we have previously demonstrated that [124I]-FIAU PET imaging of HSV-TK activity following retroviral and adenoviral (ADV-tk) transduction is feasible, selective and quantitative. The preclinical studies in this proposal will: 1) extend these studies and demonstrate selective vector imaging, 2) provide a comparison between mHSV1 (G207 and R7020) and retroviral (DCSV and SFG) vectors in appropriate experimental animal models, and 3) provide imaging data that could support and justify the initiation of clinical trials. The clinical studies are the focus of this proposal and will demonstrate that noninvasive imaging of transgene expression in target tissue can be used to monitor and facilitate the evaluation of gene therapy by defining the location, magnitude and persistence of transgene expression over time. It would also provide the opportunity to assess the spread of the vector to nontarget tissue and organs using whole body imaging techniques, and it could define the optimal time and duration of time for effective pro-drug administration.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNIZATION TO REDUCE GENITAL AND NEONATAL HERPES Principal Investigator & Institution: Bourne, Nigel; Associate Professor; Pediatrics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): The control of genital herpes will require widespread use of effective vaccines. However, if herpes simplex virus (HSV) vaccines do not achieve sterilizing immunity (prevent virus replication at the entry site) the virus will establish latency, rendering the host potentially contagious during reactivation, and allowing continued transmission. While animal studies with a variety of vaccines show that immunization does not prevent virus replication in the genital mucosa following high titer challenge, a HSV type 2 glycoprotein D vaccine protected 39-46% of seronegative women against infection in a recent clinical Trial. Since much of the spread of genital herpes occurs during periods of asymptomatic shedding when relatively little virus is present, we believe that the protection resulted because immunization increased the virus inoculum required to infect the genital mucosa. In Aim 1 we will explore this hypothesis by determining the effect of immunization with the clinical study vaccine on the virus inoculum required to infect the genital mucosa in a mouse model. In Aim 2 we will again use the threshold of infection to measure efficacy and determine whether DNA prime glycoprotein boost improves protection compared to DNA or glycoprotein only immunization. These studies are relevant because an effective vaccine will need to induce T helper type 1 (Th1) responses in addition to antibody and DNA vaccine priming with protein boosting has been shown to increase Th1 responses compared to protein only immunization. While a vaccine that increases the threshold of infection will reduce the incidence of transmission, it will not provide universal protection. In Aim 3 we will use conditions that overcome protection from infection to examine the impact of immunization on the magnitude of latent infection and recurrent disease (both clinical recurrences and virus shedding into the genital tract). These studies will provide new information about the risks of transmission from immunized hosts who become infected. Taken together, the studies in this proposal will yield new information about the capacity of HSV vaccines to reduce the spread of genital herpes. These study designs may become standard for preclinical evaluation of HSV vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTIONS
IMMUNOBIOLOGY
OF
ANTIRECEPTOR
RECEPTOR
Principal Investigator & Institution: Greene, Mark I.; Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-MAY-1986; Project End 31-OCT-2001 Summary: The PI work is concerned with the study of manipulation of corneal cell growth and the diminution of T cell dependent inflammatory responses in corneal injury and a model of uveitis. He has developed a new class of structurally designed immunologic mimetics for these studies. the compounds were designed from discrete complementarily determining regions of a particular anti-receptor antibody and another member of the immunoglobulin gene family, CD4. These molecules operate via novel mechanisms and offer the opportunity to study agonist and antagonistic effects on receptor specific functions. The small CDR form designed from the anti-receptor antibody stimulates corneal cell growth and accelerates corneal would defect closure.
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This CDR form has an opposite affect on activated T cells in which it inhibits activation. This compound will be studied in corneal damage associated with herpes simplex disease and in other studies dealing with corneal defects. The compound developed from CD4 has the ability to inhibit T cell activation. This compound will be studied in models of T cell dependent corneal inflammation and in models of uveitis. These compounds have many chemical and immunologic benefits over the intact macromolecules from which they were derived. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROGLIA
IMMUNOREGULATION
OF
HERPES
ENCEPHALITIS
BY
Principal Investigator & Institution: Lokensgard, James R.; Assistant Professor; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Herpes simplex virus 1 (HSV) is an important opportunistic pathogen in HIV-1-infected patients as well as the cause of a devastating CNS infection in normal hosts. Although immune responses to HSV have been the subject of intense investigation, the role of immune-mediated pathology in HSV-related brain damage is unknown. In this proposal, the central hypothesis to be tested is that chemokines produced by microglial cells in response to HSV infection initiate a cascade of neuroimmune responses that result in the serious brain damage seen during herpes encephalitis. To test this hypothesis, chemokine production in the brains of HSVinfected mice will be compared to that in cultures of highly purified murine glial and neuronal cells, and in murine organotypic brain slices infected with HSV. This approach will allow us to differentiate microglial cell chemokine production from that of cells of the somatic immune system. Additionally, the use of organotypic brain slice cultures will enable us to specifically deplete microglial cells for "loss-of-function" experiments. We will then investigate the neurotoxic effects of microglial cell-produced immune mediators on cultured murine neurons. Microglia-driven leukocyte trafficking into the brain will be investigated by determining if neutralizing antibodies to chemokines inhibit T-cell infiltration. The neuropathogenic role of T-cell infiltration will be studied by determining if depletion of T-cells in vivo will delay encephalitis and whether adoptive transfer of HSV-specific lymphocytes restores the encephalitis phenotype. Comparing neuropathology in brain slice cultures with and without the transfer of HSV-specific CD4 + and CD8 +lymphocytes, will allow us to distinguish between injury generated by viral infection and brain damage provoked by immunopathogenic mechanisms. Downregulation of microglial cell chemokine production through peripheral benzodiazepine (BDZ) receptor-mediated cellular deactivation will then be examined. We will determine if deactivation of microglia with BDZs suppresses the production of neurotoxic factors. Finally, we will study the effects of BDZ ligands on chemokine production, T-cell trafficking, and the development of encephalitis in vivo. These in vivo, in vitro, and ex vivo models will provide us with the ability to investigate neuropathogenesis, neuroinflammation, neurotoxicity, and neuroimmune-mediated pathology occurring during herpes encephalitis. Knowledge gained from these studies will increase our understanding of the role of microglial cells and chemokine networks that regulate brain inflammation during herpes encephalitis with the ultimate goal of finding new therapy for this serious brain infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INDUCTION OF PROTECTIVE IMMUNITY AGAINST MULTIPLE STDS Principal Investigator & Institution: Eko, Francis O.; Professor; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: (provided by applicant): Sexually transmitted diseases (STDs) are of major medical and social importance worldwide and co-infection by more than one STD is common in high-risk populations. Genital infections caused by Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2) rank among the highest STDs in the world. In fact, genital chlamydial infection is the most common bacterial STD in the United States and may cause severe irreversible complications in women, including pelvic inflammatory disease, fallopian tube scarring, ectopic pregnancy and infertility. Genital infection caused by HSV-2 is prevalent worldwide causing genital ulcerations and severe complications such as neonatal herpes and central nervous system involvement. Considering the worldwide prevalence of these STDs, vaccines offer the best approach for controlling these infections. Besides, a combination vaccine that can be administered as a single regimen to protect against multiple STDs would be highly desirable to control the rampant co-infections among STDs. Despite considerable effort, the development of an efficacious vaccine against either Chlamydia or herpes using conventional approaches has been difficult. The current paradigm for designing efficacious vaccines against these pathogens requires identification of appropriate antigens and development of effective delivery vehicles capable of eliciting high levels of Th1 response that can confer long-lasting protective immunity. The chlamydial major outer membrane protein (MOMP) and the glycoprotein D2 (gD2) of HSV-2 are highly immunogenic proteins that have been targeted as potential vaccine candidates; these proteins possess both neutralizing and T cell epitopes. We have designed a novel recombinant bacterial ghost delivery system which has inherent adjuvant properties and capable of simultaneously presenting multiple antigens to the immune system. The ultimate aim of the proposed project is to genetically design a recombinant multivalent subunit vaccine composed of Vibrio cholerae ghosts co-expressing the MOMP of C. trachomatis and the gD2 of HSV-2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INNATE CORNEAL CELL IMMUNITY TO VIRUS INFECTION Principal Investigator & Institution: Taylor, Jerry L.; Microbiol & Molecular Genetics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Infection of the cornea with herpes simplex virus (HSV) initiates an innate immune response that plays a major role in limiting virus spread. Production of interferon (IFN) and IFN-induced proteins is an important component of this innate response. Some of the IFN-inducible proteins localize to nuclear structures termed ND1Os, which are the sites of viral DNA localization and initiation of viral transcription. The aims of this grant focus on determining the mechanism of action of two of these IFN-induced proteins, PML and SP100, and the regulation of their expression in human cornea (HCS) cells. Each protein exists in multiple forms as a result of variable mRNA splicing. Our studies show that SP100B is a potent inhibitor of two HSV transcriptional transactivating proteins, VP16 and ICP4. The specificity of SP100B's inhibitory activity will be characterized by examining the action against basal expression and transactivation of a number of viral and cellular
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Herpes Simplex
promoters. Using the yeast two-hybrid system we will identify cellular protein(s) that function as mediators between SP100B and ICP4. The region of SP100B that confers repression is within a 29 amino acid domain that has the potential to be highly phosphorylated. This region will be mapped to determine whether specific amino acid phosphorylation is essential for activity. We will determine whether localization to the ND1O structure and transcriptional repressive activity are linked. The second protein to be examined is PML, a structural component of ND1Os. Two forms of PML will be evaluated alone and combined with SP100B for their contribution to the transcriptional regulation of HSV genes. The interaction of PML with the viral general transcriptional transactivator ICPO, a protein known to disrupt ND1s, will be characterized by transcription assays in transiently and stably transfected cells and by microscopic localization of green fluorescent protein-tagged forms of PML. HCS cells appear to contain high levels of PML localized to ND1Os, potentially acting to provide an elevated innate immune response. Monoclonal antibodies specific for forms of PML and SP100 will be prepared and used to identify the forms of PML and SP100 naturally present in these corneal cells and determine the changes that occur in their expression in response to IFN treatment and virus infection. These studies will characterize a potent transcriptional repressive mechanism we have identified and determine its contribution to corneal inhibition of HSV replication. This knowledge may be utilized to enhance this innate antiviral response and thereby limit initial and recurrent viral infections in the eye. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF LATENCY OF HERPES SIMPLEX VIRUS Principal Investigator & Institution: Fraser, Nigel W.; Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 31-AUG-2006 Summary: (provided by applicant) Herpes Simplex virus (HSV) can cause a wide range of diseases, including skin lesions, which are common, encephalitis which is rare, an HSV infection of the eye, which is a leading cause of blindness in the USA (400,000 cases). The seroprevalence of HSV in the U.S. adult population is very high (approximately 70%). Herpes virus infections are characterized by the ability of the virus to form latent infections in the nervous system. It is this ability, which leads to recurrent episodes of the disease causing much human suffering, which is the focus of our application. The overall goal of this proposal is to understand the mechanism of HSV latency using both a mouse model system and tissue culture studies. We have previously used a mouse model system of HSV latency to study physical state of the latent viral genome, and to initiate studies on viral gene expression during latency. From our data, we have formulated models for the mechanism of HSV-1 latency. We now wish to continue to refine these models using the techniques of molecular virology. The program consists of three scientific projects, and an administrative and two scientific cores. The scientific projects are titled: 1. Gene Expression during HSV-1 Latency and Reactivation; 3. The Role of Cellular Transcription Factors in the Regulation of HSV-1 Latency and Reactivation; 4. Herpes Simplex Virus and Neuronal Cell Interactions. Successful completion of these studies will permit the mechanisms of HSV latency to be described in more detail, allowing formulation of new strategies for the prevention of latency and recurrence. In addition, it is anticipated that the knowledge gained will continue to be of use to the fields of gene therapy and cancer therapy in the nervous system, and continue to provide more patentable findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF LATENCY OF HERPES SIMPLEX VIRUS Principal Investigator & Institution: Schaffer, Priscilla A.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objectives of the Program Project are to identify the viral and cellular factors involved in the establishment, maintenance and reactivation of herpes simplex virus type 1 (HSV-1)/ latency and to determine the roles of these factors in the latency process To achieve these objectives, the following four projects are proposed. Project 5 (Knipe) will define the mariner in which the host immediate response induced by specific viral antigens affects latent infection by HSV-1. Special emphasis will be placed on the duration of cytokine expression and the T cell response following immunization. The identity of the viral functions required for longterm effects on neuronal gene expression will be determined using mutant viral strains. The mechanisms by which the LATs down-regulate productive-cycle gene expression and ICP8 stimulates accumulation of viral DNA in neurons will also be investigated. Project 6 (Coen) will investigate the mechanisms by which various recognized blocks to viral gene expression, including the LATs, are involved in maintaining HSV-1 latency. The molecular and genetic basis for the ability of an ACVr, TK- clinical isolate to establish and reactivate from latency will be investigated to identify viral functions able to compensate for TK in latency. Changes in host cell gene expression and factors affecting these changes during HSV-1 latency in mice will also be examined. Project 4 (Schaffer) will determine the kinetics and order of viral gene expression relative to the initiation of viral DNA replication in reactivating mouse TG. The roles of oriL and oriS, and specifically the 0BP and GR binding sites in these origins, in the initiation of DNA replication during reactivation in mouse TG and in rabbits will be investigated. The identity of cdks required for reactivation of HSV-1 from latency and the effects of cdks on the transactivating activity and post- translational modification of lCP0 will be identified. Project 7 (M. Greenberg) will characterize the neurotrophins, cytokines and neuropeptides in TG neurons that support HSV replication and determine whether these molecules can regulate HSV-1 latency and reactivation in TG cell cultures. The intracellular signaling pathways activated by stimuli that induce HSV-1 reactivation, and that mediate NGF withdrawal induced reactivation in sympathetic neurons will also be investigated. Collectively, the results of these studies will provide new insights into the mechanisms by which HSV-1 latency in established, maintained and reactivated in neurons. In turn, these insights will reveal novel strategies for intervening in this poorly understood aspect of HSV-1 pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF HERPES SIMPLEX VIRUS RETINITIS Principal Investigator & Institution: Atherton, Sally S.; Professor and Chair; Cellular Biology and Anatomy; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 30-SEP-1985; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract): Following uniocular anterior chamber inoculation of the KOS strain of HSV-1 in euthymic BALB/c mice, extensive virus infection accompanied by a massive inflammatory response is observed in the anterior segment of the injected eye. However, in spite of the virus infection in the anterior segment, virus does not infect the retina of the inoculated eye. In contrast, the retina of the uninoculated eye becomes infected with virus beginning on or about day 7 p.i., and the retina of this eye is destroyed by 14 days p.i. Although there is mild anterior uveitis,
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Herpes Simplex
the anterior segment of the uninoculated eye does not become infected. The overall goal of the studies proposed in this application is to elucidate the pathogenesis of HSV-1 infection in the injected eye, the brain, and the uninjected eye following uniocular anterior chamber inoculation of HSV-1. Three specific aims will define (1) the mechanism by which direct anterior-to-posterior spread of the KOS strain of HSV-1 is prevented following uniocular anterior chamber inoculation of BALB/c mice, (2) the mechanism which prevents virus that has spread to the brain in euthymic BALB/c mice from infecting the optic nerve and retina of the injected eye, and (3) the role of T cells and cytokines during HSV-1 infection of the retina of the uninoculated eye. Information about early protection in the injected eye following anterior chamber inoculation may provide clues about why patients with HSV-1 keratitis, many of whom also have viral anterior uveitis, do not normally develop retinitis in the afflicted eye. Information about limitation of virus spread in the hypothalamus may provide insight into why virus that reaches the brain in pathways other than the trigeminal may be unable to spread to the optic nerve and retina and may help to explain why such a small number of patients with HSV-1 develop retinitis. Studies of how T cells and cytokines contribute to retinitis once virus has infected an eye may aid in design of specifically-targeted therapies to modulate an established infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF MUCOSAL IMMUNITY TO HERPES SIMPLEX VIRUS Principal Investigator & Institution: Morrison, Lynda A.; Associate Professor; Molecular Microbiol and Immun; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): Herpes Simplex virus (HSV) causes several serious human diseases including a sexually transmitted disease that significantly effects maternal and child health and may be a cofactor in the acquisition of other STDs such as AIDS. Once infected with HSV, individuals retain the virus in a latent state, from which periodic reactivation causes recurrent disease and provides an opportunity for transmission. The means to protect against HSV infection by inducing potent immune responses that can act quickly at the site of infection remains elusive. Replication-defective mutants of HSV offer a safer alternative to live virus vaccines. Because the infection does not spread in the host, these viruses also provide a unique tool to examine the induction of antiviral immune responses. Mice immunized subcutaneously or intranasally with an HSV-2 mutant virus generate immune responses that protect mice from disease and lethal infection upon genital challenge with a heterologous HSV-2 strain. It is hypothesized that immunization with replicationdefective HSV-2 generates an immune response protective against genital HSV-2 that is principally mediated by CD4+ Th1 cells. In addition, it is also hypothesized that the provision of B7 co-stimulatory molecules in infected cells will augment the immunogenicity of the replication-defective virus and improve protective capacity. In Aim 1, histochemical analysis of the vaginal mucosa and the analysis of latent genomes in the ganglia will identify the stage of pathogenesis that is blocked by the protective immune response. In Aim 2, the components of the immune response that are protective against genital challenge will be identified using knockout mice, T cell subset depletions, and cytokine analyses. In Aim 3, the role of costimulation in the induction of immune response to replication-defective virus will be investigated by construction of recombinant viruses that encode B7 molecules. This information will facilitate
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developent of immunization strategies against HSV and possibly other pathogens of the genital tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF THE HSV-1 UL42 PROTEIN Principal Investigator & Institution: Parris, Deborah S.; Professor; Medical Microbiol & Immunology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 31-MAR-2003 Summary: There is amazing conservation in the requirements for and mechanism of DNA replication among highly diverse organisms. Herpes simplex virus type 1 (HSV-1) is an excellent model system for eukaryotic DNA replication since the virus encodes most of the proteins required for this essential process and can be manipulated genetically with greater ease than higher eukaryotes. DNA polymerases are central to the process of DNA replication. A general requirement of replicative DNA polymerases is that they copy the template genome with rapidity and reasonable fidelity. A major means by which they achieve the necessary rate required for genome duplication is the use of accessory proteins to increase their processivity. The HSV-1 DNA polymerase (pol) forms a stable and specific complex with an accessory factor, UL42. Like other pol accessory proteins, UL42 increases the processivity of its cognate pol, but differs in several important ways. Its lack of requirement for clamp loading proteins distinguishes it from the toroid sliding clamps, such as PCNA and E. coli pol III beta. Furthermore its intrinsic ability to bind to DNA is unique among all other known processivity factors, including those which don't require clamp loaders, such as thioredoxin, the processivity factor for T7 bacteriophage pol. The latter ability also presents an apparent paradox for known mechanisms of processivity, in that UL42 could also serve as a brake to elongation. The major long-term goal of the proposed studies is to elucidate the mechanism by which UL42 increases pol processivity, and the resulting impact this mechanism has on other properties of the pol, including parameters required for fidelity of DNA replication. A combination of biochemical, biophysical, and genetic approaches will be used to address four specific aims: 1) To determine the effect of reduced DNA binding by mutant UL42 proteins on rates of elongation and pol processivity using transient kinetic analysis and direct binding studies; 2) To determine the effect of processivity and proof-reading capability on the individual parameters which affect fidelity in vitro, including nucleotide selection, failure to extend mismatched termini, and excision of mismatched primer termini, using kinetic analysis to dissect these processes; 3) To determine the biological impact of changes in fidelity parameters (caused by changes in processivity) on the frequency and types of mutations which occur during origin (ori)- dependent DNA replication in vivo; 4) To determine the ability of the ori-binding protein, UL9, which interacts with UL42, to facilitate the assembly and/or processivity of pol/UL42 complexes on blocked synthetic primer/templates. Functional analogs of HSV-1 pol and UL42 are encoded by all human herpesviruses, including Kaposi sarcoma-associated virus (HHV-8), Epstein Barr virus, and human cytomegalovirus, all of which are significant human pathogens, particularly for cancer and immuno- suppressed patients. It is important to understand an the mechanism of UL42 action since disruption of the pol/UL42 complex has been proposed for development of antivirals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
42
Herpes Simplex
•
Project Title: MOLECULAR ANALYSIS OF HSV-I REACTIVATION FROM LATENCY Principal Investigator & Institution: Sawtell, Nancy M.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-DEC-2002 Summary: The long term goal of the proposed research is to define the molecular mechanisms involved in the transition from latent to lytic herpes simplex virus (HSV) gene transcription. They previously developed the hyperthermic stress (HS) reactivation model which is unique in that the production of infectious virus is detectable within 1214 hours after the induction stimulus. Using this model, they have identified what is likely to be a key event in the regulation of reactivation, namely the up regulation of ICPO within 1 hour post HS. Insight into the molecular regulation of reactivation must ultimately be obtained from analysis of individual latently infected neurons. They have developed a new method, contextual expression analysis, CXA, to obtain quantitative information about the DNA and RNA in individual cells within solid tissues. In this proposal, the power of PCR and RT PCR will be harnessed through CXA to construct a molecular definition of latency and reactivation. Their ability to precisely quantify the number of latently infected neurons in the ganglia and examine the RNA and DNA content will allow them to meaningfully evaluate wild type and genetically engineered mutant strains to achieve the following specific aims: (1) Determine the impact of the number of latently infected neurons and/or the number of viral genome copies within individual latently infected neurons and/or the number of viral genome copies within individual latently infected neurons upon the initiation and progression of HS inducted reactivation in vivo; (2) Utilize CXA-RNA strategies to characterize viral transcription during latency and following HS induced reaction at the neuronal population and single cell level; (3) Determine the biological significance and biochemical basis of the rapid up regulation of the ICPO gene following HS induced reaction in vivo. Defining the regulatory mechanisms by which the "latent" repository of viral genetic information periodically give rise to infectious virus is central to understanding this important aspect of the viral life cycle. Insight into these viral functions could contribute significantly toward our ability to design effective vaccines, develop treatments for the prevention of recurrent disease, and efficiently transfer, maintain and regulate foreign genes in the human host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MOLECULAR GENETICS OF HSV 1 CAPSIDS Principal Investigator & Institution: Desai, Prashant; Pharmacol & Molecular Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-DEC-1993; Project End 31-AUG-2003 Summary: A genetic and biochemical study of herpes simplex virus type 1 (HSV-1) capsids is proposed. Major goals of the proposed experiments are to identify conformation changes in capsid structure that occur during B capsid maturation, to identify residues in the molecules that cause the changes, and to identify interactions between the molecules through which the changes may be mediated. Capsid shells are composed of three essential proteins; VP5, the major capsid shell component, and VP19C-VP23, a complex which interacts with and stabilizes VP5. The UL26 (VP24 and 21) and the more abundant UL26.5 (22a) gene products specify the protease activity (VP24), and the scaffold (22a and probably 21) on which the shell is assembled via interactions with VP5. Specific Aim 1. Residues of UL26 and UL26.5 gene products
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43
known to interact with VP5 will be altered that (1.1). block protease cleavage at the maturation site, or (1.2). prevent essential interactions with VP5. Compensatory genetic changes, presumably in VP5, will be selected that allow the blocks to be overcome. Specific Aim 2. Changes in shape (spherical to icosahedral) may accompany B capsid maturation. Mutant viruses possibly blocked at steps in the maturation process will be examined during infection of non-permissive cells by electron microscopy, cellular immunofluorescence using a VP5 specific antibody, and by SDS-PAGE analysis of capsid proteins following sedimentation analysis. Specific Aim 3. The size, shape and oligomeric status of the major scaffold molecule (22a) will be determined. The yeast GCN4 and HIV-1 gp160 residues that specify basic leucine zipper motifs may be used to replace the self-interactive domain. The transdominance of mutant viruses will be evaluated. Specific Aim 4. Residues of VP26 that interact with VP5 will be identified using VP26-negative capsids incubated with wild-type and mutant forms of VP26 synthesized in vitro. Specific Aim 5. Studies will be pursued to determine the structure of the VP19C-VP23 complex by x-ray crystallography. A number of insertions in VP19C coding sequences will aid the identification of residues of VP19C that interact with VP23 and with VP5. In vitro synthesized products of VP19C and VP23 will be assayed by coimmunoprecipitation and a capsid binding assay, respectively. Specific Aim 6. Experiments are proposed to package viral DNA into capsids, and to determine the direction of packaging of DNA into capsids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETICS OF HSV REACTIVATION Principal Investigator & Institution: Bloom, David C.; Assistant Professor; Molecular Genetics & Microbiol; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: provided by applicant): Herpesviruses are ubiquitous and are responsible for significant human mortality and suffering both in terms of initial infections and (even more so) recurrences. In addition, with increasing occurrences of immunosuppressive disorders, a corresponding increase in the frequency of clinically significant initial and latent herpesvirus infections arise. Therefore, the long-term objective of this project is to gain a functional understanding of the herpesvinis-encoded genes involved in latency and reactivation - knowledge that is fundamental to the rational design of interventive therapies. We have identified a region of the genome termed the "reactivation critical region" (rcr) that is required for epinephrine-induced reactivation. The primary focus of this proposal is to characterize the functional role sequence elements in the rcr of the Herpes simplex virus type 1 (HSV- 1) genome play in reactivation of infections latent in sensory ganglia neurons. The overriding hypothesis of this study is that the HSV rcr facilitates reactivation by regulating gene expression from the latent genome allowing the initiation of acute gene expression during reactivation. Using a molecular genetic approach involving specifically engineered viral recombinants, we will follow the transcriptional and replicative processes of HSV- 1 reactivation in the rabbit corneaepinephrine model to link viral genetics with processes in animals. Specifically, the proposed studies will test three potential mechanisms by which the rcr functions to facilitate reactivation: a) the rcr acts as a modulator of transcription which facilitates reactivation by regulating the expression of LAT, ICPO and/or ICP4, b) the rcr is a target of methylation and/or cellular factors that regulate transcription during latency and reactivation, and c) the rcr acts as a non-coding functional RNA that regulates gene expression via a dosage compensation-like mechanism. These three mechanisms are not mutually exclusive and it is likely an interplay between these regulatory elements is
44
Herpes Simplex
necessary for the maintenance of and reactivation from latency. This work will lead to the identification of viral target(s) of host factors that communicate stress stimuli leading to reactivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISEASES
MOLECULAR
MECHANISMS
OF
STRESS-RELATED
ORAL
Principal Investigator & Institution: Chambers, Donald A.; Professor & Head; Molecular Biol/Oral Diseases; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Our long term goals are to understand the molecular interactions governing neuroimmunology and their relationship to infectious oral diseases, e.g., recurrent Herpes simplex virus infection, HIV and periodontal diseases, and wound healing: processes associated with stress and/or enhanced fluxes of catecholamines (CAs) and immune dysfunction. Previous studies by others and us demonstrated association between CAs and diminished immune function. These investigations focus on the hypothesis that the nervous system interacts with the immune system in part through the agency of CAs, sympathetic neurotransmitters most closely associated with immune cells and their reservoirs. This grant investigates specific molecular mechanisms involved in CA-mediated immune gene expression; in particular, the CA-mediated downregulation of mRNAs necessary for regulated Tcell function. To do this, we will use well characterized cloned murine cells of T cell lineage (S49 lymphosarcoma, EL-4 cells and a CD8+ cell line) to study the CA-mediated dynamics of mRNAs of genes associated with immune regulation (the Beta-adrenergic receptor and the cytokines TNFa, IL-2 and IFN-y) down-regulated by cAMP, the second messenger associated with CA-beta-adrenergic signaling. Specific Aim I determines whether these genes are down-regulated by CA exclusively through mRNA destabilization or in concert with other mechanisms and continues investigation of our paradigm for mRNA destabilization that a (CA/cAMP/PKA) protein kinase mechanism is central to regulation of mRNA stability this Aim will a) identify the RNA target sites in CA/cAMP/PKA modulated mRNAs that affect their stability and b) investigate the mechanisms through which CAs modulate mRNA destabilization in T cells by characterizing the proteins that affect mRNA stability. Specific Aim II will explore new data that suggest the hypothesis that CM modulates specific gene products involved in the activation and function of Herpes simplex (HSV) specific cytotoxic T lymphocytes. Completion of these Specific Aims provides insight into exciting and unique mechanisms whereby CAs down-modulate mRNAs for effector proteins of immune cells to decrease the capacity of these cells to respond to external signals and HSV infection and could allow development of peptides and oligonucleotide therapies designed to inhibit the effect of endogenous stressors and/or enhance immune function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINES
NEUROENDOCRINE
REGULATION
OF
HSV
1
INDUCED
Principal Investigator & Institution: Ortiz, Griselle C.; Periodontology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003
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Summary: Herpes simplex virus type 1 (HSV-1) infections lead to misery and discomfort for millions of persons worldwide. Cell-mediated immunity has been pointed out as an important component of the host's defense against herpes simplex virus. It has been demonstrated that the activation of the hypothalamic-pituitary-adrenal axis by stressful events results in an elevation of corticosteroids in the serum that may impair immune function. Although the skin is the primary site for recurrent HSV-1 infections we still do not understand the immunological mechanisms in which stress modulates immune responses toward cutaneous herpes simplex virus infections. Cytokines are important mediators of inflammation and viral clearance in herpes virus infections, but despite their importance in antigen specific recruitment of immune cells and in the inflammatory process, little is known about local cytokine expression during the course of a cutaneous herpes viral infection. During stress events, activation of the hypothalamic-pituitary-adrenal axis occurs and catecholamines and glucocorticoids are produced. Glucocorticoids have an immunosuppressive action such as inhibiting the activities of neuropeptides and cytokines. The hypothesis that we intent to test in this proposal is that restraint stress will induce changes in the pathophysiology of a HSV-1 infection by depressing early inflammatory mediators which will lead to a severe and longer lasting infections. Gene expression of pro-inflammatory cytokine will be downregulated leading to a decrease in inflammatory cell infiltrate, which will lead to an increased number of infective viral particles at the site of the infection. We also hypothesize that restraint stress will induce a down-regulation of the gene expression of Th1 derived cytokines, causing a shift into a Th2 mediated response. Shifting to a h2 mediated response has been shown to make the host more susceptible to severe HSV-1 infections. An elevated level of glucocorticoids in plasma is the underlying factor in the depressed immune response. The following specific aims have been developed in order to test the hypothesis: In Specific Aim I, we will evaluate and characterize the HSVinfection severity and healing time in restrained animals. We will perform histological evaluations of the inflammatory cells present in the tissues at different times during the course of the infection; we will also evaluate for the presence of viral particles at the site of the infection, and we conduct assays to determine infectious viral titers. Later in Specific Aim II, we will focus our attention on the gene expression of pro-inflammatory cytokines and Th1 and Th2 cytokine profiles. We will study the gene expression of IL1alpha, TNF-alpha, pro-inflammatory cytokines involved in the recruitment of inflammatory cells; Th1 profile cytokines IL-2, INF-gamma, which have important proliferative functions for T-cells and potent antiviral effects, respectively, Downregulation of IL-2 and INF-gamma may induce shifting of a TH1 mediated response to a Th2 dominated response. Correlations of the clinical, histological, and immunological findings will be done in order to understand the mechanisms in which restrain stress modulates HSV-1 infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL MICROBIOCIDES FROM CARRAGEENAN Principal Investigator & Institution: Phillips, David M.; Senior Scientist; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2005 Description (provided by applicant): This Project will study the efficacy of two novel carrageenan-based formulations, zinc- carrageenan (Zn-carrageenan) and lignosulfonic acid (LSA) carrageenan (LSA-carrageenan). Preliminary results indicate that these formulations are significantly more efficacious than carrageenan in blocking HIV in vitro and herpes simplex-2 (HSV -2) infection in mice. Since there is no known assay that
46
Herpes Simplex
is predictive of a microbicide's efficacy, the applicant proposes to utilize a number of different in vitro assays and animal systems. In vitro assays will involve a peripheral blood mononuclear cells (PBMC) assay and another assay that employs an established epithelial cell line derived from the human cervix. Because there is a variety of different HIV strains that are sexually transmitted, as well as the fact that the viral genome is constantly changing, the formulations will be assayed for activity against a number of different strains and clades of HIV. Additionally, formulations will be evaluated in a number of animal systems. The HSV-2/mouse system has proven to be a straightforward and consistently reproducible method for evaluating several parameters. Formulations will be evaluated in this system for vaginal and rectal antiviral activity, duration of activity, and efficacy in protecting against pre- and post-viral challenge. Another system, developed by the PL, has shown that lymphocytes and macrophages can traffic from the vaginal vault and subsequently be detected in lymph nodes and spleen. This finding supports the concept that HIV -infected mononuclear cells in semen may infect women by study by Masurier et al. (J. Virol. 1998:72:78227829), which presented evidence that when active or inactivated virus is instilled into the vagina of a mouse, it can subsequently be detected by RT -PCR in the lymph nodes. The applicant will utilize his modified HIV/Mouse system and the Cell Trafficking system to compare Zn-carrageenan, LSA-carrageenan, and the carrageenan-only formulation, Carraguard for efficacy in preventing HIV transport and cell trafficking from the vaginal vault. The applicant feels that the proposed in vitro assays and animal systems in conjunction with the proposed research of our co-investigators is the most well rounded approach to the pre-clinical development of novel microbicide against HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OCULAR HSV INFECTION-LATENCY AND PATHOGENESIS Principal Investigator & Institution: Thompson, Richard L.; Molecular Genetics, Biochemistry & Microbiology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Herpes simplex virus (HSV) is the leading infectious agent causing blindness world wide. This human viral pathogen invades the nervous system, seeding host neurons with viral genetic information. This genetic information is a stable repository from which the virus reinitiates lytic infection which can result in recurrent or persistent corneal inflammation, scarring and ultimately blindness. The molecular mechanisms underlying this process are not well understood but remain central to the prevention and control of HSV. The long-term goal of the proposed research is to define the molecular mechanisms involved in the establishment of herpes simplex virus (HSV) latency. Using a novel single cell PCR assay to obtain quantitative information about the number of neurons containing the viral genome, we have demonstrated that a 2.3kb fragment residing within the latency associated transcript (LAT) gene provides a critical function for the establishment of latent infections (Thompson and Sawtell J.Virol.71 :5432, 1997). Data has been recently generated indicating a significant increase in neuronal death in ganglia infected with mutants lacking this 2.3kb fragment. Consistent with the decreased neuronal survival in the peripheral nervous system, LAT null mutants are more neuroinvasive. Pfu/LD50 experiments demonstrate LAT null mutants in strain l7syn+ are 100-fold more virulent when compared to wild type or genomically rescued isolates. Our ability to precisely quantify the number of latently infected neurons in the ganglia and the number of viral genomes in those individual neurons
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will be exploited to evaluate genetically engineered mutant strains to define the regulatory mechanisms by which locus attenuates virulence increases the latent repository of viral genetic information, and promotes reactivation and thereby recurrent disease. The information gained in these studies will permit the design of more effective vaccines and interventive drug therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OCULAR COSTIMULATION
HSV-1,
STROMAL
KERATITIS,
&
T
CELL
Principal Investigator & Institution: Kwon, Byoung S.; Professor; Ophthalmology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Herpes simplex virus type 1 (HSV-1) corneal infection leads to establishment of a latent infection in the sensory and autonomic ganglia. HSV-1 reactivates at intervals and causes recurrent corneal infection. Repeated inflammation in the corneal stroma can lead to herpetic stromal keratitis (HSK), an immune inflammatory process that results in blindness. For optimal activation, T cells require costimulation in addition to antigen receptor signals. Constitutive receptors such as CD28 are known to provide costimulation to naive T cells. We have also shown that 4-1BB, an inducible receptor, provides costimulation to activated and memory T cells. However, whether costimulatory receptors play a role in acute, latent, and recurrent HSV-1 infection, and in HSK, is not known. It is also not known whether induction of Tcell energy by blocking costimulation can prevent HSK. Our goals are to determine the role of T-cell costimulatory molecules in herpes infection, to identify factors involved in the pathogenesis of HSK, and to investigate the therapeutic potential of blocking costimulation in HSK. Three specific aims are proposed: 1] Test the hypothesis that the costimulatory receptors, 4-1BB and CD28, are involved in modulating acute HSV-1 infection, latency, and recurrence using 4-1BB- and/or CD28-deficient mice. 2] Determine the roles of the costimulatory receptors 4-1BB and CD28 in the pathogenesis of HSK. 3] Test the hypothesis that blocking costimulation is effective in preventing HSK. This approach (inhibition of costimulation) should be both specific and nontoxic, compared to the use of immunosuppressive drugs. These studies will aid in understanding the immunological mechanisms involved in the blinding eye condition, HSK, and allow development of strategies for the treatment of this and other ocular inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEPTIDE INHIBITION OF HSV ENTRY Principal Investigator & Institution: Brandt, Curtis R.; Professor; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Description (provided by applicant): Herpes simplex virus remains a significant public health threat despite the availability of antivirals to treat HSV infections. The incidence of genital HSV infection has doubled in the last decade and it is estimated that 22% of all people over 12 years of age in the US are infected with HSV-2. HSV infection also is a significant risk factor for acquisition of HIV infection. It has been known for some time that the presence of ulcerative genital disease increases. Since both HIV and HSV cause persistent infections, the ideal control strategy is to prevent infection. Many people choose not to use condoms and nonoxynol-9 enhances HIV infection by damaging the
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Herpes Simplex
vaginal mucosa. Alterative preventative strategies are desperately needed. The applicant has discovered a series of peptides that block HSV infection in vitro and one, EB, which is virucidal, also blocks infection in vivo. The applicant?s collaborators have shown that the peptides also block HIV and HPV infection. The first overall goal of Project II is to further the development of the lead peptides that the applicant has discovered and move them closer to clinical trials. He will determine the mechanism of action of the peptides, screen derivatives to identify more potent peptides, test in vitro toxicity in several cell types, and test efficacy in an animal model of HSV epithelial disease. The second overall goal is to use the peptides as tools to study processes involved in HSV entry. The applicant will test binding of the antiviral peptides to the purified entry proteins of HSV(gB, gD, and gH/gL), use the peptides to block entry and analyze the step or steps that are blocked. He will use phage display methods in conjunction with Core A to identify peptides that specifically bind to the purified glycoproteins. These peptides will then be tested for antiviral activity and used in studies to determine the role of the proteins in entry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTECTION OF GENITAL MUCOSA AND GANGLIA AGAINST HSV-2 Principal Investigator & Institution: Milligan, Gregg N.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JUL-2001 Summary: Greater than Herpes simplex virus type 2 (HSV-2) now infects the genital tracts of approximately one in five Americans. Strategies to prevent new HSV-2 infections are complicated by its ability to initiate a latent infection in the sensory ganglia, periodically reactivate, and cause recurrent lesions or asymptomatic virus shedding in genital tissues thus increasing its chances of infecting new hosts. Effective vaccines are needed to prevent the establishment of latency within the sensory ganglia. Unfortunately, little is known about the immune mechanisms which protect the sensory ganglia. In animal models, previous genital inoculation with HSV-2 elicits immunity which protects the sensory ganglia from reinfection, thus serving as a paradigm for an effective HSV-2 vaccine. The long term aims of this proposal are to use a murine model of genital HSV-2 inoculation to understand the types of immune mechanisms responsible for protection, how these mechanisms work at the molecular level, and how to elicit these responses to provide long term protection. The results of these studies will provide important information for the rational design of vaccines to protect against HSV-2. In the first aim, a recombinant HSV-2 strain expressing green fluorescent protein (HSV-2 gfp) will be used as a marker to determine if HSV-specific T lymphocytes prevent HSV-2 from reaching the sensory ganglia, thus preventing the establishment of latency. Quantification of HSV-2 gfp infected ganglionic neurons by UV microscopy and HSV-2 gfp genomes in the ganglia by quantitative PCR will be used to demonstrate the role of specific T cell subsets in preventing acute and latent HSV-2 infection of the ganglia. In the second aim, an antibody deficient strain of mice (muMT) will be used to determine the role of HSV-specific antibody in protection of the sensory ganglia. Purified IgG and IgA fractions of HSV-specific sera will be administered to HSVimmune muMT mice to determine the efficacy of specific antibody isotypes in completing the protection of HSV-immune muMT mice against the establishment of latent HSV-2 infection. In the third aim, the ability of immune responses elicited by inoculation of distal mucosal or systemic sites to protect the sensory ganglia will be tested. The ability of inoculation at these sites to elicit long term memory immune
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responses within the vaginal mucosa and associated genital lymphoid tissue which can be rapidly recalled for protection of the vaginal mucosa and sensory ganglia will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RANDOMIZED TRIAL OF HIV/STI PREVENTION IN ZIMBABWE YOUTH Principal Investigator & Institution: Cowan, Frances M.; U of L University College London University College London London, Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The aim of the project is to implement and rigorously evaluate an innovative adolescent HIV/STI prevention program involving school students, professional peer educators, teachers, parents, rural health clinics and the wider community, by means of a community randomized trial. Primary objective: To measure the effectiveness of an adolescent HIV prevention intervention delivered to secondary school students and the wider community in reducing the incidence of HIV1, Herpes simplex virus type 2 (HSV2) and unintended pregnancy among the students. Secondary objectives: I) To use a combination of quantitative and qualitative research methods to explore the evolution of sexual behavior in adolescents in rural Zimbabwe. II) To assess the impact of the intervention on knowledge and attitudes regarding reproductive and sexual health, reported behavior, and measures of self-efficacy. III) To determine through rigorous process evaluation whether these programs are delivered as intended. IV) To refine and assess the validity of research instruments for measuring sexual behavior in Zimbabwean adolescents. V) To examine through rigorous process evaluation acceptability and feasibility of providing VCT in rural community settings. VI) To study the epidemiology of HSV2 infection among adolescents, and to measure the extent to which HSV2 facilitates acquisition of HIV infection. Trial Design: 30 communities (60 schools) will be randomly allocated to either early or deferred program implementation. The impact of the program will be measured in a cohort of 6,600 students aged >12 (median age 15), who will be followed for 4 years (median age 19). Participants will be surveyed at the start of the project, after 30 months and after 4 years. At each survey they will complete a questionnaire and provide a saliva sample (and females a urine sample). The impact of the program on cumulative incidence of HIV-1 and HSV2 infection, and unintended pregnancy as well as on reported sexual behavior will be determined. A detailed process evaluation of the program will be conducted to inform wider program implementation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: REGULATION OF GENE EXPRESSION BY DNA BINDING LIGANDS Principal Investigator & Institution: Dervan, Peter B.; Professor; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2001; Project Start 01-JUL-1989; Project End 31-MAR-2003 Summary: Sequence specific DNA binding small molecules that can permeate human cells could potentially regulate transcription of specific genes. When one considers the fact that within the next few years the entire human genome will be mapped and sequenced and, coupled to the remarkable discoveries in biology and human medicine which link human disease to specific genes, fundamental research on these DNA binding ligands could lead to reagents for research in functional genomics and, importantly, a new class of human therapeutics. Our objective has been to elucidate
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Herpes Simplex
chemical principles for the design of small molecules which bind predetermined doublehelical DNA sequences with the affinity and specificity of proteins in order to target predetermined sites within the human genome. The Py-Im-Hp polyamides, the result of a 20-year chemistry program to understand the physical organic principles for DNA recognition, are cell permeable ligands only a few percent the size of a protein which have the affinity and specificity of transcription factors. These synthetic DNA binding ligands have been shown to penetrate human cells, traffic to the nucleus, find the promoter DNA sequences of transcriptionally active genes and inhibit gene expression. In this next funding period, the scope and limitations of this approach with regard to polyamide configuration, size, cell types, and different families of transcription factors will be examined. Cancer and viral genes important in human health will be targeted. With regard to specific aims, polyamides will be designed and synthesized to: (1) inhibit transcription of human breast cancer oncogenes (Her-2/neu), (2) inhibit transcription of Herpes Simplex Virus (HSV), (3) regulate c-fos promoter activity in a mouse, (4) upregulate transcription by creation of polyamide-peptide conjugates as artificial transcription activators, (5) inhibit DNA replication in E coli and yeast, (6) chemically modify coding regions of genes by the design of polyamide-mitomycin and nitrogen mustard conjugates, (7) inhibit viral integration of murine leukemia virus into a host chromosome, and (8) enhance cell uptake further by polyamides with membrane translocation peptide sequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF GENE EXPRESSION IN HSV INFECTED CELLS Principal Investigator & Institution: Wilcox, Kent W.; Associate Professor; Microbiol & Molecular Genetics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-JUL-1980; Project End 31-MAR-2003 Summary: Herpes simplex virus (HSV) infection often results in a recurrent disease that manifests as skin lesions in the facial or genital area. Herpes virus infections are a leading cause of blindness and fatal endemic enecphalitis. Reactivation of herpes is a serious problem for individuals with immune systems compromised by chemotherapy or HIV infection. Productive infection and the consequent cell destruction by herpes virus requires activation of viral gene expression by a viral protein designated ICP4 (IE175, Vmw175). Initial characterization of the structure and function of ICP4 suggests that it is an ideal target for anti-viral drugs. ICP4 has been conceptually divided into 5 regions on the basis of comparative sequence analysis with related members of the alphaherpesvirus family. These proteins share extensive homology in regions 2 and 4. There is evidence for a transactivation domain in region 1, a DNA binding domain in region 2, and nuclear localization signal in region 3. Although all 5 domains are required for full ICP4 activity, no specific functions have been assigned to regions 4 and 5. The long-term goal of this investigation is to define the structural basis for the functions of ICP4. The specific aims of this project are (1) to characterize the ICP4 during productive infection; and (4) to investigate interactions between ICP4 and a component of the 20S proteasome. The roles of TAD-1 in productive infection and pathogenesis will be determined by infection of cells and animals with a TAD-1 negative mutant. TAD-1 will be further defined by analysis of the effect of point mutations in TAD-1 on transactivation. Coimmunoprecipitation assays with mutant proteins will be performed to define the residues in region 4 that are responsible for TBP/TFIIB interactions. The biological significance of the TBP/TFIIB binding sites in region 4 will be investigated by complementation assays and analysis of viral mutants. Interactions between ICP4 and
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proteasomes will be investigated in transfected and infected cells. The results of these analysis will be integrated into a working model for ICP4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF HSV GENE EXPRESSION DURING LATENCY Principal Investigator & Institution: Coen, Donald M.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objective of this project has been to investigate the roles of viral DNA replication, replication proteins, and gene expression in the interaction of herpes simplex virus (HSV) with the mammalian nervous system, especially virus latency. Latency is the most fascinating biological property of the virus and its most important clinical feature. Understanding HSV latency is sure to reveal novel features of HSV and the nervous system. Such information is highly relevant to antiviral drugs that target DNA replication, vaccines, and potential agents to cure HSV infections. The proposed research will investigate regulation of viral gene expression during latency (aim 1). Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assays will be used to measure expression of different classes of transcripts and potential regulatory molecules in ganglia and single cells. Cloning of cDNAs will complement the RT-PCR studies. These assays, mutant viruses from the Schaffer and Knipe laboratories, and transgenic mice overexpressing viral sequences will be used to study mechanisms of repression mediated by the HSV latency-associated transcript locus. Anti-HSV drugs will be used to test a model for regulation of viral gene expression by DNA replication. The mechanisms by which drug resistant mutants retain pathogenicity will be explored (aim 2). Frameshift mutations in the thymidine kinase gene that arise in clinical isolates will be tested for effects on latency. Cosmid-based methods will be used to map alleles of clinical isolates that compensate for loss of TK in latency. Finally, changes in host gene expression, which may affect latency, will be studied in collaboration with the Knipe laboratory and Millennium Pharmaceuticals (aim 3). Array technologies will be used to identify changes in host gene expression and RT-PCR assays and viral mutants will be used to examine the time-course, localization, and requirements for these changes. The proposed experiments should shed light on viral and cellular factors involved in the establishment, maintenance, and reactivation of HSV latency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF THE LAT-ICP0 LOCUS IN REGULATING HSV LATENCY Principal Investigator & Institution: Halford, William P.; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Recurrent infections with herpes simplex viruses (HSV) are a significant clinical problem. Fundamental to understanding the nature of recurrent herpetic disease is determining precisely how HSV alternates between the two phases of its dual life cycle, latency and reactivation of productive infection. The LATICP0 locus plays a central role in the regulation of HSV-1 latency and reactivation. The genes that encode for the latency-associated transcripts (LATs) and infected cell polypeptide 0 (ICP0) form a continuous locus in the repeated regions of the HSV genome. Specifically, the LAT and ICP0 genes lie on opposite strands of HSV-1's doublestranded DNA genome and share a significant overlap. Thus, the abundant LATs can
52
Herpes Simplex
hybridize to 0.75 kilobases of complementary sequence in ICP0 mRNA. While the antisense arrangement of the LAT-ICP0 locus has long been recognized, the hypothesis that LAT RNAs serve as "antisense repressors" of ICP0 gene expression has not been rigorously analyzed. The juxtaposition of the LAT and ICP0 genes mirrors their opposing roles in latency. While LAT RNAs facilitate the maintenance of HSV latency, expression of ICP0 is necessary and sufficient to induce HSV-1 reactivation. Conversely, failure to express ICP0 is highly conducive to HSV genomes entering a transcriptionally repressed state. Thus, antisense repression of ICP0 mRNA translation is one mechanism by which LATs may facilitate the maintenance of latency. The goal of this research proposal is to evaluate the concept that LAT RNAs and ICP0 form a pair of mutually dependent, opposite regulators that are the yin and yang of HSV latency. Specifically, genetic evidence will be obtained to test the hypothesis that "All viral proteins that induce HSV-1 reactivation in the trigeminal ganglion cell culture model achieve this phenotype via (a) induction of ICP0, (b) suppression of LAT transcription, or (c) both." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROPREVALLENCE /INCIDENCE OF GENITAL HERPES IN UGANDA Principal Investigator & Institution: Nakku-Joloba, Edith; New Mulago Hospital Po Box 5346, Std Clinicward 12 Kampala, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Prevalence of herpes simplex type 1 and 2 virus (HSV-1 and 2) infection is high worldwide and is highest in developing countries like Uganda. International and local health organizations have called for studies to characterize genital herpes epidemiology in sub-Saharan Africa. Population estimates are needed for policy, for planning interventions, for valid measures of the effect of interventions and for research on new therapies and potential vaccines. The overall goal of this study is to determine the burden of infection and assess the modifiable risk factors associated with Herpes simplex types 1 and 2 infection in Kampala, Uganda with an aim of prevention of spread and relief of those who suffer with genital herpes. The proposed study will aim i) To estimate the age and sex specific prevalence of Herpes simplex type 1 and 2. ii). To estimate the incidence of Herpes simplex type 1 and 2 in an inception cohort of HSV-2 negative persons in an urban population in Uganda and iii) to identify modifiable risk factors associated with Herpes simplex types 1 and 2 prevalence and incidence in this population. The proposed study will be a twostage stratified random population sample survey of female and male participants 15 to 65 years old in Kawempe division of Kampala District. To estimate prevalence of HSV-1 and 2, a cross-sectional serological survey at baseline will be done using type specific ELISA tests for herpes simplex type 1 and 2. Incidence will be assessed in an inception cohort of HSV-2 negative persons by 6 monthly testing for HSV-2. Risk factors for genital herpes will be assessed using a standardized questionnaire to collect information on age, sociodemographic characteristics, sexual behavior, sexual partner characteristics such as age differentials, and HIV infection status. Incidence densities and relative risks will be calculated from new HSV-2 infection and risk factors that predispose to HSV-2 incidence such as age, sex, (gender), sexual behavior, and HIV infection analyzed in a Cox proportional hazards model. By conducting a population study in an urban area in a country where rural studies show high prevalence we will describe the epidemiology genital herpes, gaining new knowledge about genital herpes in urban Uganda and highlighting the modifiable risk factors which can be targeted for effective interventions.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECIFICITY OF HEPARAN SULFATE FOR HERPES INFECTION Principal Investigator & Institution: Liu, Jian; Medicinal Chemistry and Natural Products; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant) The long term goal of this project is to understand the roles of cell surface heparan sulfate in contributing herpes simplex viral infection. Heparan sulfate is a highly sulfated polysaccharide with very complicated saccharide sequences, and is present on the mammalian cell surface and in the extracellular matrix in a large quantity. Although heparan sulfate is a known important cell-surface molecule involved in assisting herpes virus infection for a long time, the relationship between the saccharide structure and its role in assisting herpes viral infection is poorly understood. We propose to conduct a series of biochemical studies to elucidate the structural specificity of the 3-O-sulfated heparan sulfate, which is generated by three different heparan sulfate 3-O-sulfotransferase (3-OST) isoforms, for the binding to herpes envelope glycoprotein D (gD). In particular, we plan to carry out the following projects: 1. Isolation and characterization of the gD-binding oligosaccharides generated by isoform 3 (3-OST-3). We plan to prepare the gD-binding oligosaccharide by incubating purified 3-OST-3 enzyme with a heparan sulfate oligosaccharide library. The gD-binding oligosaccharide will be purified using anion exchange HPLC and gDaffinity column. The structure of the gD-binding oligosaccharide will be determined by chemical and enzymatic degradation approaches coupled with matrix assisted laser desorption/ionization mass spectrometry. We also plan to examine the effect of the purified gD-binding oligosaccharide on viral entry into the cell using a cell-based assay. 2. Characterization of the structures of the gD-binding sites generated by isoform 2 and isoform 4 (3-OST-2 and 3-OST-4). We plan to express and purify 3-OST-2 and 3-OST-4 enzymes. We will also determine the structures of the gD-binding sites within 3-OST-2 and 3-OST-4 modified heparan sulfate. Both 3-OST-2 and 3-OST-4 have recently proved to assist herpes simplex virus 1 entry into the cells, suggesting that 3-OST-2 and 3-OST4 provide binding sites for gD. In addition, studies of the distribution of 3-OST-2 and 3OST-4 revealed that both enzymes are highly expressed in human brains. We speculate that herpes virus may utilize 3-OST-2 and 3-OST-4 modified heparan sulfate to infect human brains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STUDIES OF HERPES SIMPLEX VIRUS GLYCOPROTEINS Principal Investigator & Institution: Cohen, Gary H.; Professor and Chair; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-1981; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's abstract) For the two herpes simplex viruses (HSV-1 and HSV-2), four glycoproteins designated gB, gD and a complex of gH/gL are essential for virus entry. A fifth glycoprotein, gC, though not essential, is important for facilitating initial attachment by binding to cell surface heparin sulfate proteoglycans. gD triggers entry by interacting with one of several different cellular receptors. gB and gH/gL are necessary for fusion of the envelope with the plasma membrane. The long-term objective of the research efforts of Drs. Cohen and Eisenberg is to understand the mechanism by which these glycoproteins interact with each other
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Herpes Simplex
and with cell molecules to mediate HSV entry. Within this proposal, they propose three specific aims: 1) to study immunological and biochemical properties of soluble gD, alone or in combination, with two of its receptors, HveA (a TNF receptor) or HveC (an adhesion molecule in the Ig superfamily); 2) to study the gD-receptor interaction when either the ligand or the receptor (or both) is membrane bound; and 3) to study events in virus entry that occur as a consequence of gD-receptor interactions. The investigators suggest that downstream interactions of the virus with the plasma membrane may involve gB and gH/gL of the virus and may additionally involve other cellular molecules. They have cloned the ectodomains of gD, gB, gH/gL, HveA and HveC into a baculovirus expression system and/or mammalian cells and have expressed and obtained purified proteins. In Aim 1, they will use these proteins to solve the structure of gD alone and/or in combination with receptor and/or antibody by X-ray diffraction analysis. They will map antibody and receptor binding domains on gD and look for conformational changes in gD that occur as a result of receptor binding. In Aim 2, they will use quantitative assays that present gD or its receptor in the context of a membrane and study the interaction of the other protein as a soluble form. One approach will be to bind HSV to an ELISA plate and then determine if added soluble receptor inhibits the infection of cells that are added in fluid phase. Such studies will indicate that they are evaluating receptor binding to a viable virus. In a second approach, they will bind virions to a biosensor chip and flow soluble receptor across the chip to measure receptor-virus interactions. A third approach will be to express the receptor in the murine leukemia virus (MuLV)-receptor pseudotype system and use these particles to study binding of gDt. In Aim 3, they will look for interactions among soluble forms of gD, gB and gH/gL in the presence and absence of gD receptors. In addition, they will study a series of gD/gH hybrid molecules for their ability to function in HSV infection in place of gD or gH/gL. Finally, they will study mutant forms of HSV including those that no longer require HveA or HveC for entry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF MECHANISM OF ACTION AND BIOAVAILABILITY Principal Investigator & Institution: Birt, Diane; Professor and Chair; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2002; Project Start 22-JUL-2002; Project End 31-MAY-2007 Summary: Aims: 1) Evaluation of the effects of Echinacea and Hypericum in animal models: non-specific and specific immune responses to herpes simplex-1 virus, inflammation and cell proliferation. 2) Explore the mechanisms of action of the above using cell culture systems 3) Evaluate the bioavailability of constituents of Hypericum (hypericin, pseudohypericin) and Echinacea (alkylamides, echinacoside). Researchers on this project include Diane Birt as the PI and 5 co-PI's (Susan Carpenter, Joan Cunnick, Suzanne Hendrich, Marian Kohut and Patricia Murphy). The bulk of the work will be done by two assistant scientists and one associate scientist. This project includes in vitro, in vivo and human studies. Facilities for this project are located in several buildings on the Iowa State University Campus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TARGETTING DIFFUSE LIVER METASTASES WITH HERPES VIRUS Principal Investigator & Institution: Tanabe, Kenneth K.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 07-JAN-2000; Project End 31-DEC-2002
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Summary: Current therapuetic modalities for patients with liver metastases are clearly inadequate. To date, virtually all cancer gene therapy research using viruses have focused on replication- incompetent viruses. However, replication-competent herpes simplex virus type 1 (HSV) holds promise as a potentially effective oncolytic agent. The principal anti-tumor activity of replication-competent HSV results from viral replication within tumor cells, resulting in cell destruction, as well as production of progeny virions that can directly infect adjacent tumor cells. In addition, HSV thymidine kinase activation of the prodrug ganciclovir enhances the antitumor activity. The strategy of restricting HSV replication to cancer cells represents a novel paradigm. The hypotheses to be examined are 1) HSV can be genetically modified to restrict its replication to CEAexpressing cells; 2) Treatment of diffuse liver metastases with intrasplenic administration of HSV will result in significant tumor reduction with limited spread of viral infection; and 3) Pre-existing immunity to HSV will limit spread of viral infection without reducing anti-tumor efficacy. In Specific Aim 1 construction of an HSV mutant (designated HSVceaalpha) will be completed. This vector is engineered such that an immediate-early gene that is critical for HSV replication is regulated by the human CEA promoter, thereby limiting HSVceaalpha replication to CEA-expressing cells. The ability of HSVceaalpha to replicate and cause cytopathic effects will be examined in primary cultures of normal human tissues, CEA- positive and CEA- negative colon carcinomas, and in human skin xenografts. In Specific Aim 2 the efficacy and toxicity of treating liver metastases with replication-conditional HSV will be examined. Several complementary assays will be used to detect HSV replication in tumor and non-tumor tissues after intrasplenic HSV administration to mice bearing diffuse liver metastases. The effects of viral dose, systemic ganciclovir administration, and initial tumor volume on spread of viral infection and animal surivival will be measured. In Specific Aim 3 we will analyze the effect of the host immune system on treatment of liver metastases with replicationconditional HSV. We will first examine how pre-existing immunity influences both the spread of HSV infection after treatment of liver metastases and the anti- tumor efficacy. We will subsequently examine the effect of individual components of the immune system on viral spread and anti-tumor efficacy. In concert, these studieds will provide a basis for development of clinical trials with HSV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE GENETICS OF HSV-1 REACTIVATION Principal Investigator & Institution: Feldman, Lawrence T.; Associate Professor; Microbiology and Immunology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: Herpes Simplex Virus Type I (HSV-1) infects humans orofacially, causing a gingivostomatis of the mouth and a keratitis of the eye. HSV-1 infections are highly prevalent in the population. Approximately eighty percent of adults in the U.S. are seropositive for HSV-1. Following a primary infection, this virus establishes a latent infection of the trigeminal from which it can reactivate causing a recurrence of the disease. Our present understanding of the pathogenesis of both latency and reactivation at the molecular level is incomplete. Research to date has established the importance of the LAT region in viral reactivation from the latent state. However no clear molecular role for the LAT region's contribution to reactivation has been defined, nor has the role of the LAT region in establishing a latent infection been determined. This proposal is aimed at the construction of more precisely defined mutations within the LAT region. Current viral mutants are defective in more than one function. A second goal of the
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Herpes Simplex
proposal is to employ a variety of PCR and non-PCR-based techniques to study the ability of these mutant viruses to establish a latency infection when compared with the wild type virus. The final area of interest is to construct recombinant viruses which are unable to reactivate from the latent state and to learn from the structure of those viruses how the LAT region contributes to a reactivation event. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF ATP HYDROLYSIS IN HSV-1 TERMINASE ACTIVITY Principal Investigator & Institution: Duffy, Carol L.; Microbiology and Immunology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The goal of this project is a thorough analysis of the ATPase activity associated with the herpes simplex virus type 1 packaging enzyme, or terminase. The process of DNA packaging is both conserved among members of the Herpesviridae and distinct from cellular processes. Thus studies on the HSV-1 terminase will provide knowledge important for the generation of anti-viral agents for herpesviruses associated with a number of life-threatening diseases. The hydrolysis of ATP is required for herpesvirus DNA packaging. The UL15 and UL28 proteins have been proposed to comprise the HSV-1 terminase and, therefore, to possess the many activities required for DNA packaging including ATPase activity. The specific aims of this proposal utilize biochemical and genetic approaches to identify and analyze the ATPase center of the HSV-1 terminase. Purified UL15 and UL28 proteins will be tested for ATPase activity and the kinetics of ATP hydrolysis will be determined. ATPinteracting residues will be identified through the sequencing of protease-derived peptides from 8-N3-[alpha-32p]ATP-photolabeled protein. Proteins containing amino acid changes in ATP-interacting residues will be generated, purified, and studied to confirm the importance of those residues to ATP hydrolysis. Finally, HSV-1 mutants carrying the above mutations will be generated and examined in vivo to identify specific DNA packaging activities that require the newly discovered ATPase center. These studies will greatly increase the understanding of the process of DNA packaging by all herpesviruses and will extend our knowledge of ATP-driven molecular motors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THERAPEUTIC RECURRENCE
VACCINES
TO
REDUCE
OCULAR
HSV
Principal Investigator & Institution: Nesburn, Anthony B.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-DEC-2003 Summary: (Adapted from the applicant's abstract): This proposal proposes to reduce the incidence of herpes induced blindness through therapeutic vaccination. In the previous research period, the investigator has indicated therapeutic vaccine efficacy in terms of statistically significant that reduced recurrent HSV-1 ocular disease and HSV-1 shedding. The investigator has hypothesized that the therapeutic vaccine efficacy seen is due to local ocular/mucosal immune response rather than a systemic immune response. The investigator's group has produced four papers directly related to their work on therapeutic vaccination. All papers have been submitted at this time (none accepted). The specific aims to be addressed in the present application are (1) to test the hypothesis that therapeutic vaccine efficacy and duration against recurrent ocular HSV-1 can be extended by periocular booster inoculations with a subunit vaccine, or with HSV-1 DNA
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ocular vaccines or live HSV-1 ocular vaccines; (2) to test the hypothesis that therapeutic vaccine efficacy against recurrent ocular HSV-1 is due to common mucosal immunity rather than just local ocular mucosal immunity; and (3) to verify the hypothesis that sIgA is the specific mucosal immune response most important for therapeutic vaccine efficacy against recurrent ocular HSV-1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTIONAL REGULATION Principal Investigator & Institution: Herr, Winship; Assistant Director/Dean; Cold Spring Harbor Laboratory 1 Bungtown Road Cold Spring Harbor, Ny 11724 Timing: Fiscal Year 2002; Project Start 21-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Tumor progression involves changes in transcriptional regulation that result in altered states of gene expression. Central to the process of transcriptional regulation is the activation of transcription by RNA polymerases I, II, and III. This transcriptional activation involves the interplay of sitespecific activators bound to sites near or far from the transcriptional start site with basal factors bound to core-promoter elements located near the transcriptional start site. This project represents the fusion of two current projects-Enhancer Function and Viral Transactivation-and its overall goal is to understand how site-specific activators and core-promoter-binding basal factors communicate amongst themselves and with each other to regulate transcription. We use herpes simplex virus (HSV) to probe these mechanisms. When HSV infects a cell, the infecting virion deposits a transcriptional activator called VP16 into the infected cell. VP16 initiates a cascade of viral gene transcription by directing formation of a multiprotein-DNA complex, called the VP16induced complex, with two cellular coregulators-Oct-1, a POU-domain transcriptional activator, and HCF-1, a chromatin-associated regulator of cell proliferation-on HSV immediate-early promoters. In uninfected cells, Oct-1 plays important roles in activation of RNA polymerase II and III transcription by different core-promoter-binding basal factors in different promoter contexts and HCF-1 plays one or more important roles in promoting cell proliferation through association with chromatin. We study these cellular and viral proteins together and separately to understand the mechanisms of transcriptional regulation in human cells. We will determine the structure and function of the herpes-simplex-virus VP16-induced complex and its constituent members, HCF-1, Oct-1, and VP16; elucidate the roles of basal core-promoter-binding factors in both RNA polymerase II and III transcription; and identify mechanisms of transcriptional activation domain function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSPORT OF HERPES SIMPLEX VIRUS IN OCULAR TISSUES Principal Investigator & Institution: Lavail, Jennifer H.; Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-JUL-1978; Project End 31-MAR-2007 Summary: (provided by applicant): Understanding the mechanisms of axonal transport of neurotropic viruses is the key to understanding and controlling their spread in the nervous system. To multiply and spread, to move initially from the site of entry and later to the site of release, Herpes simplex virus (HSV) must use neuronal host cell proteins and mechanisms. Our understanding of the interplay of specific viral proteins that piggyback on the mechanisms and of the neuronal proteins that are exploited, is critical but almost nonexistent. In this application we continue to focus on the
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anterograde transport of HSV. Based on our previous results, our hypothesis is that the nucleocapsid and envelope components of HSV are independently transported in the axon and that the components require specific kinesin related proteins. 1) We have begun to examine the transport of the nucleocapsid and envelope components. To do this we have developed two viral mutant strains and revertants that will facilitate our research into these transport mechanisms. 2) In this proposal we shall continue these studies and carry out co-immunoprecipitation assays to identify the motor proteins associated with the nucleocapsid component. 3) We shall also determine whether or not the virus egresses from the cell by budding, after the envelope proteins are delivered to the axon membrane and the nucleocapsids cluster near that region of membrane. These results will provide important new cell biological information about the recognition signals of particular organelles. They will also have significant clinical benefits. The anterograde transport of HSV to the cornea in human herpetic keratitis results in severe consequences, including corneal scars, glaucoma and possibly encephalitis. Our results will provide new insight into the identification of viral and host proteins necessary for viral envelope and nucleocapsid transport and a rational basis for the design of innovative antiviral drugs for prevention and intervention. Furthermore, the genome of HSV can be altered to serve as a vector for introduction of novel genes into the nervous system. Our results will elucidate the mechanisms that target the vector to particular neuron types and to particular regions of infected neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE TRANSMISSION
OF
MODIFIED
LACTOBACILLI
TO
BLOCK
HSV
Principal Investigator & Institution: Chang, Chia-Hwa; Osel, Inc. Suite 14 Santa Clara, Ca 95054 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-AUG-2003 Summary: (provided by applicant): Genital herpes infection is extremely common throughout the world and continues to increase in incidence, Genital herpes is caused by the sexual transmission of herpes simplex virus type 2 (HSV-2), although a smaller, but increasing, percentage of cases are caused by herpes simplex virus type 1 (HSV-1) Genital herpes infection is associated with a range of clinical sequlae, including many that are serious in nature. The lack of effective measures to impede HSV transmission underlies the widespread escalation of the genital herpes epidemic. We are developing a novel approach to block HSV transmission in women. This approach, termed MucoCept HSV, involves genetic modification of human vaginal isolates of lactobacilli, the common bacterium found within the vaginal mucosal microflora of healthy women. These bacteria are being modified to produce a decoy HSV receptor that has the capacity to bind, trap, and inactivate HSV within the mucosal layer before it is transmitted to host cell and tissues. As such, this represents a novel and potentially powerful approach to prevent the transmission of HSV. As outlined in the present application, we propose to genetically modify vaginal-derived lactobacilli to express the HSV receptor, HveC, either covalently attached to the cell wall of the bacterium, or secreted into the surrounding biofilm matrix. This approach will use technology that has already been used by our group for the successful expression of other heterologous mammalian proteins in these same strains of lactobacilli. We propose to subsequently demonstrate the capacity of the expressed HveC protein to neutralize HSV infectivity of susceptible cultured cell lines. If achieved successfully, these studies will position us to undertake Phase II studies to assess the efficacy of these modified bacteria to reduce HSV
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transmission in vivo, as well as to optimize stable expression of the HveC protein as a major component of the clinical development plan for this product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRAL AND MOLECULAR CHEMOTHERAPY OF MALIGNANT CNS TUMORS Principal Investigator & Institution: Buchsbaum, Donald J.; Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAY-2007 Summary: This multi-disciplinary group of investigators has several years' experience working together designing and characterizing viral vector approaches to gene therapy of malignant brain tumors. A major focus has been producing and testing both nonreplicative and replicative adenovirus (Ad) and conditionally replicative herpes simplex virus (HSV) vectors that express foreign gene products within infected tumor cells. These studies have been conducted at both the in vitro and in vivo levels to demonstrate proof-of-principle, safety and efficacy in experimental mouse models of intracranial gliomas. We have conducted Phase I and III clinical trials using retrovirus, Ad and HSV administered intratumorally in patients with malignant gliomas. In keeping with the translational theme of this SPORE application, this project seeks to design and deploy effective viral vector therapies of malignant glioma by utilizing rational combinations of foreign gene-viral vectors, oncolytic virus and irradiation., defined by additive, synergistic or antagonistic interactions determined for these various modalities. Aim 1 seeks to optimize the timing and dose of irradiation to achieve greater viral replication and spread and/or enhanced foreign gene expression in glioma cells and in intracranial experimental gliomas. In athymic nude mice. Aim 2 will develop and characterize both replicative HSV and replicative Ad that expression the pro-drug converting enzyme cytosine deaminase and optimize its use in intracranial preclinical models of malignant gliomas in combination with systemic 5-fluorocytosine. Other genetic constructs (uracil phosphoribosyl transferase) and drugs (dihydropyrimidine inhibitors) that facilitate appropriate 5-FU incorporation into host cell DNA synthesis pathways will also be tested to improve the therapeutic effect. Further, the radiation sensitization properties of certain pro-drugs products (5-FU) will be characterized to achieve a greater anti-glioma effect. Aim 3 will combine findings in Aims 1 and 2 to design and test strategies that rationally combine intratumoral viral vector injection, systemic pro-drug administration and low dose external beam irradiation to achieve the most effective and safe antiglioma therapy (ies). Aim 4 will translate our findings in preclinical models for brain tumor therapy into pilot, Phase I and Phase II clinical trials in patients with malignant gliomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VIRION HOST SHUTOFF PROTEIN OF HERPES SIMPLEX VIRUS Principal Investigator & Institution: Ross, Jeffrey; Professor and Chair; Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Herpes Simplex
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Project Title: VIRUS-CELL INTERACTIONS & HERPES SIMPLEX VIRUS INFECTION Principal Investigator & Institution: Montgomery, Rebecca I.; Inst for Molecular Virology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): The ultimate goal of this project is to define the mechanism of herpes simplex virus (HSV) invasion of human cells to establish productive infection. The two serotypes of HSV combined, infect -80 percent of the world adult population. Once infected, a person is infected with these viruses for life. HSV causes a variety of diseases: cold sores, genital lesions resulting from sexually transmitted virus, blindness from ocular infection, severe disseminated disease in newborns, and encephalitis. Disease can resuk from initial infection or re-occurring infection by HSV. Understanding how the virus gains entry into cells to initiate infection can lead to new therapies to block virus infection, prevent disease due to re-occurring infection, or help in the design of vaccines to promote inimunity to HSV infection. In this grant we will further characterize the HveA co-receptor, a human protein that mediates HSV entry into cells, to determine areas of the molecule necessary for virus interactions and promotion of virus entry. We will identify biologically relevant glycosaminoglycans and proteoglycans that enhance virus entry via HveA and characterize their role in the HSV entry pathway. In addition, we will continue the search for other cell products used by HSV to gain entry into cells. The results obtained from these studies will advance our understanding of the cellular components HSV interacts with to gain entry into cells, the cell-virus interactions that promote entry, and methods of enhancing or preventing HSV entry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “herpes simplex” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for herpes simplex in the PubMed Central database: •
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A 371-nucleotide region between the herpes simplex virus type 1 (HSV-1) LAT promoter and the 2-kilobase LAT is not essential for efficient spontaneous reactivation of latent HSV-1. by Perng GC, Slanina SM, Ghiasi H, Nesburn AB, Wechsler SL.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190031
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A 437-base-pair deletion at the beginning of the latency-associated transcript promoter significantly reduced adrenergically induced herpes simplex virus type 1 ocular reactivation in latently infected rabbits. by Hill JM, Garza HH Jr, Su YH, Meegalla R, Hanna LA, Loutsch JM, Thompson HW, Varnell ED, Bloom DC, Block TM.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191932
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A Gene Capable of Blocking Apoptosis Can Substitute for the Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene and Restore Wild-Type Reactivation Levels. by Perng GC, Maguen B, Jin L, Mott KR, Osorio N, Slanina SM, Yukht A, Ghiasi H, Nesburn AB, Inman M, Henderson G, Jones C, Wechsler SL.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135864
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A Herpes Simplex Virus Type 1 [gamma]34.5 Second-Site Suppressor Mutant That Exhibits Enhanced Growth in Cultured Glioblastoma Cells Is Severely Attenuated in Animals. by Mohr I, Sternberg D, Ward S, Leib D, Mulvey M, Gluzman Y.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114924
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A Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutant with Increased Virulence and Reduced Spontaneous Reactivation. by Perng GC, Slanina SM, Yukht A, Drolet BS, Keleher W Jr, Ghiasi H, Nesburn AB, Wechsler SL.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103911
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A Multicenter Phase I/II Dose Escalation Study of Single-Dose Cidofovir Gel for Treatment of Recurrent Genital Herpes. by Sacks SL, Shafran SD, Diaz-Mitoma F, Trottier S, Sibbald RG, Hughes A, Safrin S, Rudy J, McGuire B, Jaffe HS.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105979
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A Net + 1 Frameshift Permits Synthesis of Thymidine Kinase from a Drug- Resistant Herpes Simplex Virus Mutant. by Hwang CB, Horsburgh B, Pelosi E, Roberts S, Digard P, Coen DM.; 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44015
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A Novel Cellular Protein, p60, Interacting with both Herpes Simplex Virus 1 Regulatory Proteins ICP22 and ICP0 Is Modified in a Cell-Type-Specific Manner and Is Recruited to the Nucleus after Infection. by Bruni R, Fineschi B, Ogle WO, Roizman B.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104158
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A novel function for human factor C1 (HCF-1), a host protein required for herpes simplex virus infection, in pre-mRNA splicing. by Ajuh P, Chusainow J, Ryder U, Lamond AI.; 2002 Dec 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136956
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A Novel Herpes Simplex Virus Type 1 Transcript (AL-RNA) Antisense to the 5[prime prime or minute] End of the Latency-Associated Transcript Produces a Protein in Infected Rabbits. by Perng GC, Maguen B, Jin L, Mott KR, Kurylo J, BenMohamed L, Yukht A, Osorio N, Nesburn AB, Henderson G, Inman M, Jones C, Wechsler SL.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155148
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A Null Mutation in the Gene Encoding the Herpes Simplex Virus Type 1 UL37 Polypeptide Abrogates Virus Maturation. by Desai P, Sexton GL, McCaffery JM, Person S.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114600
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A Null Mutation in the UL36 Gene of Herpes Simplex Virus Type 1 Results in Accumulation of Unenveloped DNA-Filled Capsids in the Cytoplasm of Infected Cells. by Desai PJ.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112442
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A Protective Role of Locally Administered Immunostimulatory CpG Oligodeoxynucleotide in a Mouse Model of Genital Herpes Infection. by Harandi AM, Eriksson K, Holmgren J.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140825
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A Protein Encoded by the Herpes Simplex Virus (HSV) Type 1 2-Kilobase LatencyAssociated Transcript Is Phosphorylated, Localized to the Nucleus, and Overcomes the Repression of Expression from Exogenous Promoters When Inserted into the Quiescent HSV Genome. by Thomas SK, Lilley CE, Latchman DS, Coffin RS.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136061
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A Virus with a Mutation in the ICP4-Binding Site in the L/ST Promoter of Herpes Simplex Virus Type 1, but Not a Virus with a Mutation in Open Reading Frame P, Exhibits Cell-Type-Specific Expression of [gamma]134.5 Transcripts and LatencyAssociated Transcripts. by Lee LY, Schaffer PA.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109655
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Accumulation of Herpes Simplex Virus Type 1 Early and Leaky-Late Proteins Correlates with Apoptosis Prevention in Infected Human HEp-2 Cells. by Aubert M, Rice SA, Blaho JA.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113998
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Accumulation of Viral Transcripts and DNA during Establishment of Latency by Herpes Simplex Virus. by Kramer MF, Chen SH, Knipe DM, Coen DM.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124594
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Activation of cJUN N-Terminal Kinase by Herpes Simplex Virus Type 1 Enhances Viral Replication. by McLean TI, Bachenheimer SL.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112860
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Activation of Interferon Response Factor-3 in Human Cells Infected with Herpes Simplex Virus Type 1 or Human Cytomegalovirus. by Preston CM, Harman AN, Nicholl MJ.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114459
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Acyclovir Cream for Treatment of Herpes Simplex Labialis: Results of Two Randomized, Double-Blind, Vehicle-Controlled, Multicenter Clinical Trials. by Spruance SL, Nett R, Marbury T, Wolff R, Johnson J, Spaulding T.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127288
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Alpha and Gamma Interferons Inhibit Herpes Simplex Virus Type 1 Infection and Spread in Epidermal Cells after Axonal Transmission. by Mikloska Z, Cunningham AL.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114768
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Alpha/Beta Interferon and Gamma Interferon Synergize To Inhibit the Replication of Herpes Simplex Virus Type 1. by Sainz B Jr, Halford WP.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136787
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Alphaherpesvirus Proteins Related to Herpes Simplex Virus Type 1 ICP0 Affect Cellular Structures and Proteins. by Parkinson J, Everett RD.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102039
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Altering the Expression Kinetics of VP5 Results in Altered Virulence and Pathogenesis of Herpes Simplex Virus Type 1 in Mice. by Tran RK, Lieu PT, Aguilar S, Wagner EK, Bloom DC.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153803
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Amplification of Reiterated Sequences of Herpes Simplex Virus Type 1 (HSV-1) Genome To Discriminate between Clinical HSV-1 Isolates. by Maertzdorf J, Remeijer L, Van Der Lelij A, Buitenwerf J, Niesters HG, Osterhaus AD, Verjans GM.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85683
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An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. by Perng GC, Thompson RL, Sawtell NM, Taylor WE, Slanina SM, Ghiasi H, Kaiwar R, Nesburn AB, Wechsler SL.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189003
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An Enhanced Packaging System for Helper-Dependent Herpes Simplex Virus Vectors. by Stavropoulos TA, Strathdee CA.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109935
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An Important Role for Major Histocompatibility Complex Class I-Restricted T Cells, and a Limited Role for Gamma Interferon, in Protection of Mice against Lethal Herpes Simplex Virus Infection. by Holterman AX, Rogers K, Edelmann K, Koelle DM, Corey L, Wilson CB.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104449
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An Intertypic Herpes Simplex Virus Helicase-Primase Complex Associated with a Defect in Neurovirulence Has Reduced Primase Activity. by Barrera I, Bloom D, Challberg M.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124597
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Analysis of conserved domains of UL41 of herpes simplex virus type 1 in virion host shutoff and pathogenesis. by Strelow LI, Leib DA.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190531
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Analysis of HCF, the Cellular Cofactor of VP16, in Herpes Simplex Virus-Infected Cells. by LaBoissiere S, O'Hare P.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111518
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Analysis of Individual Human Trigeminal Ganglia for Latent Herpes Simplex Virus Type 1 and Varicella-Zoster Virus Nucleic Acids Using Real-Time PCR. by Cohrs RJ, Randall J, Smith J, Gilden DH, Dabrowski C, van der Keyl H, Tal-Singer R.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112425
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Analysis of Protein Expression from within the Region Encoding the 2.0-Kilobase Latency-Associated Transcript of Herpes Simplex Virus Type 1. by Lock M, Miller C, Fraser NW.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114134
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Analysis of the 2-kilobase latency-associated transcript expressed in PC12 cells productively infected with herpes simplex virus type 1: evidence for a stable, nonlinear structure. by Rodahl E, Haarr L.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191235
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Analysis of the Phosphorylation Sites of Herpes Simplex Virus Type 1 Regulatory Protein ICP27. by Zhi Y, Sandri-Goldin RM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104088
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Anterograde Transport of Herpes Simplex Virus Proteins in Axons of Peripheral Human Fetal Neurons: an Immunoelectron Microscopy Study. by Holland DJ, Miranda-Saksena M, Boadle RA, Armati P, Cunningham AL.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112870
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Anterograde Transport of Herpes Simplex Virus Type 1 in Cultured, Dissociated Human and Rat Dorsal Root Ganglion Neurons. by Miranda-Saksena M, Armati P, Boadle RA, Holland DJ, Cunningham AL.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111661
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Antiviral Activity of a Selective Ribonucleotide Reductase Inhibitor against Acyclovir-Resistant Herpes Simplex Virus Type 1 In Vivo. by Duan J, Liuzzi M, Paris W, Lambert M, Lawetz C, Moss N, Jaramillo J, Gauthier J, Deziel R, Cordingley MG.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105657
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Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo. by Aoki H, Akaike T, Abe K, Kuroda M, Arai S, Okamura R, Negi A, Maeda H.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162640
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Application of Competitive PCR to Cerebrospinal Fluid Samples from Patients with Herpes Simplex Encephalitis. by Domingues RB, Lakeman FD, Mayo MS, Whitley RJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105021
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Application of the Intracellular Gamma Interferon Assay To Recalculate the Potency of CD8 + T-Cell Responses to Herpes Simplex Virus. by Kumaraguru U, Rouse BT.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112059
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Assembly and Organization of Glycoproteins B, C, D, and H in Herpes Simplex Virus Type 1 Particles Lacking Individual Glycoproteins: No Evidence for the Formation of a Complex of These Molecules. by Rodger G, Boname J, Bell S, Minson T.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113967
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Assembly of Infectious Herpes Simplex Virus Type 1 Virions in the Absence of FullLength VP22. by Pomeranz LE, Blaho JA.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102043
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Assembly of the Herpes Simplex Virus Capsid: Preformed Triplexes Bind to the Nascent Capsid. by Spencer JV, Newcomb WW, Thomsen DR, Homa FL, Brown JC.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109620
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Assembly of the Herpes Simplex Virus Procapsid from Purified Components and Identification of Small Complexes Containing the Major Capsid and Scaffolding Proteins. by Newcomb WW, Homa FL, Thomsen DR, Trus BL, Cheng N, Steven A, Booy F, Brown JC.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104203
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Association of herpes simplex virus regulatory protein ICP22 with transcriptional complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires
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posttranslational modification by the U(L)13 proteinkinase. by Leopardi R, Ward PL, Ogle WO, Roizman B.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191165 •
ATP Depletion Blocks Herpes Simplex Virus DNA Packaging and Capsid Maturation. by Dasgupta A, Wilson DW.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104443
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ATP-Dependent Localization of the Herpes Simplex Virus Capsid Protein VP26 to Sites of Procapsid Maturation. by Chi JH, Wilson DW.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111482
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Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice. by Sundaresan P, Hunter WD, Martuza RL, Rabkin SD.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111891
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Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation of Intracerebral Injection in Nonhuman Primates. by Hunter WD, Martuza RL, Feigenbaum F, Todo T, Mineta T, Yazaki T, Toda M, Newsome JT, Platenberg RC, Manz HJ, Rabkin SD.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112710
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Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System. by LaVail JH, Tauscher AN, Aghaian E, Harrabi O, Sidhu SS.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155024
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B7 Costimulation Plays an Important Role in Protection from Herpes Simplex Virus Type 2-Mediated Pathology. by Thebeau LG, Morrison LA.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153796
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BAC-VAC, a novel generation of (DNA) vaccines: A bacterial artificial chromosome (BAC) containing a replication-competent, packaging-defective virus genome induces protective immunity against herpes simplex virus 1. by Suter M, Lew AM, Grob P, Adema GJ, Ackermann M, Shortman K, Fraefel C.; 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23055
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B-myb Promoter Retargeting of Herpes Simplex Virus [gamma]34.5 Gene-Mediated Virulence toward Tumor and Cycling Cells. by Chung RY, Saeki Y, Chiocca EA.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104282
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Calcium Phosphate Nanoparticles Induce Mucosal Immunity and Protection against Herpes Simplex Virus Type 2. by He Q, Mitchell A, Morcol T, Bell SJ.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120054
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Capsid Structure of Kaposi's Sarcoma-Associated Herpesvirus, a Gammaherpesvirus, Compared to Those of an Alphaherpesvirus, Herpes Simplex Virus Type 1, and a Betaherpesvirus, Cytomegalovirus. by Trus BL, Heymann JB, Nealon K, Cheng N, Newcomb WW, Brown JC, Kedes DH, Steven AC.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115914
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CD4 T-Cell Responses to Herpes Simplex Virus Type 2 Major Capsid Protein VP5: Comparison with Responses to Tegument and Envelope Glycoproteins. by Koelle DM, Schomogyi M, McClurkan C, Reymond SN, Chen HB.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113250
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cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 UL42 DNA Synthesis Processivity Factor. by Advani SJ, Weichselbaum RR, Roizman B.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114607
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Cell-to-Cell Spread of Wild-Type Herpes Simplex Virus Type 1, but Not of Syncytial Strains, Is Mediated by the Immunoglobulin-Like Receptors That Mediate Virion Entry, Nectin1 (PRR1/HveC/HIgR) and Nectin2 (PRR2/HveB). by Cocchi F, Menotti L, Dubreuil P, Lopez M, Campadelli-Fiume G.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111902
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Cellular Transcription Factors Enhance Herpes Simplex Virus Type 1 oriS-Dependent DNA Replication. by Nguyen-Huynh AT, Schaffer PA.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109584
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Characterization of a Nerve Growth Factor-Inducible Cellular Activity That Enhances Herpes Simplex Virus Type 1 Gene Expression and Replication of an ICP0 Null Mutant in Cells of Neural Lineage. by Jordan R, Pepe J, Schaffer PA.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110163
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Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential. by De Logu A, Williamson RA, Rozenshteyn R, Ramiro-Ibanez F, Simpson CD, Burton DR, Paolo Sanna P.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105301
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Characterization of Herpes Simplex Virus-Containing Organelles by Subcellular Fractionation: Role for Organelle Acidification in Assembly of Infectious Particles. by Harley CA, Dasgupta A, Wilson DW.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114030
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Characterization of Herpes Simplex Viruses Selected in Culture for Resistance to Penciclovir or Acyclovir. by Sarisky RT, Quail MR, Clark PE, Nguyen TT, Halsey WS, Wittrock RJ, Bartus JO, Van Horn MM, Sathe GM, Van Horn S, Kelly MD, Bacon TH, Leary JJ.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114085
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Chimeric Nectin1-Poliovirus Receptor Molecules Identify a Nectin1 Region Functional in Herpes Simplex Virus Entry. by Cocchi F, Lopez M, Dubreuil P, Campadelli Fiume G, Menotti L.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115042
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cis-acting elements involved in transcriptional regulation of the herpes simplex virus type 1 latency-associated promoter 1 (LAP1) in vitro and in vivo. by Soares K, Hwang DY, Ramakrishnan R, Schmidt MC, Fink DJ, Glorioso JC.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190496
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Civamide (cis-Capsaicin) for Treatment of Primary or Recurrent Experimental Genital Herpes. by Bourne N, Bernstein DI, Stanberry LR.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89543
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Cleavage in and around the DR1 Element of the a Sequence of Herpes Simplex Virus Type 1 Relevant to the Excision of DNA Fragments with Length Corresponding to One and Two Units of the a Sequence. by Umene K.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114302
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Clinical utility of a nested nucleic acid amplification format in comparison to viral culture for the diagnosis of mucosal herpes simplex infection in a genitourinary medicine setting. by Coyle PV, O'Neill HJ, McCaughey C, Wyatt DE, McBride MO.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57742
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Colocalization of the Herpes Simplex Virus 1 UL4 Protein with Infected Cell Protein 22 in Small, Dense Nuclear Structures Formed prior to Onset of DNA Synthesis. by Jahedi S, Markovitz NS, Filatov F, Roizman B.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112558
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Comparative Evaluation of Colorimetric Microtiter Plate Systems for Detection of Herpes Simplex Virus in Cerebrospinal Fluid. by Tang YW, Rys PN, Rutledge BJ, Mitchell PS, Smith TF, Persing DH.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105189
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Comparative evaluation of microplate enzyme-linked immunosorbent assay versus plaque reduction assay for antiviral susceptibility testing of herpes simplex virus isolates. by Safrin S, Palacios E, Leahy BJ.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163250
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Comparative Performance of Herpes Simplex Virus Type 2-Specific Serologic Assays from Meridian Diagnostics and MRL Diagnostics. by Ribes JA, Hayes M, Smith A, Winters JL, Baker DJ.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88422
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Comparison of a direct antigen enzyme immunoassay, Herpchek, with cell culture for detection of herpes simplex virus from clinical specimens. by Verano L, Michalski FJ.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228171
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Comparison of a Monoclonal Antibody-Blocking Enzyme-Linked Immunoassay and a Strip Immunoblot Assay for Identifying Type-Specific Herpes Simplex Virus Type 2 Serological Responses. by Van Doornum GJ, Slomka MJ, Buimer M, Groen J, Van den Hoek JA, Cairo I, Vyse A, Brown DW.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95927
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Comparison of Adjuvant Efficacy of Herpes Simplex Virus Type 1 Recombinant Viruses Expressing TH1 and TH2 Cytokine Genes. by Osorio Y, Ghiasi H.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154018
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Comparison of Chemicon SimulFluor Direct Fluorescent Antibody Staining with Cell Culture and Shell Vial Direct Immunoperoxidase Staining for Detection of Herpes Simplex Virus and with Cytospin Direct Immunofluorescence Staining for Detection of Varicella-Zoster Virus. by Chan EL, Brandt K, Horsman GB.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96170
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Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model. by Field HJ, Tewari D, Sutton D, Thackray AM.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162693
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Comparison of Polymorphism of Thymidine Kinase Gene and Restriction Fragment Length Polymorphism of Genomic DNA in Herpes Simplex Virus Type 1. by Nagamine M, Suzutani T, Saijo M, Hayashi K, Azuma M.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87019
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Comparison of Two Enzyme-Linked Immunosorbent Assays and One Rapid Immunoblot Assay for Detection of Herpes Simplex Virus Type 2-Specific Antibodies in Serum. by Groen J, Van Dijk G, Niesters HG, Van Der Meijden WI, Osterhaus AD.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104643
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Comparison of Washing and Swabbing Procedures for Collecting Genital Fluids To Assess Cervicovaginal Shedding of Herpes Simplex Virus Type 2 DNA. by NdjoyiMbiguino A, Ozouaki F, Legoff J, Mbopi-Keou FX, Si-Mohamed A, Onas IN, Avoune E, Belec L.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156498
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Complement Depletion Facilitates the Infection of Multiple Brain Tumors by an Intravascular, Replication-Conditional Herpes Simplex Virus Mutant. by Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN, Chiocca EA.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111999
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Confirmation of Low-Titer, Herpes Simplex Virus-Positive Specimen Results by the Enzyme-Linked Virus-Inducible System (ELVIS) Using PCR and Repeat Testing. by Patel N, Kauffmann L, Baniewicz G, Forman M, Evans M, Scholl D.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85862
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Conservation of Type-Specific B-Cell Epitopes of Glycoprotein G in Clinical Herpes Simplex Virus Type 2 Isolates. by Liljeqvist JA, Svennerholm B, Bergstrom T.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87630
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Construction, Phenotypic Analysis, and Immunogenicity of a UL5/UL29 Double Deletion Mutant of Herpes Simplex Virus 2. by Da Costa X, Kramer MF, Zhu J, Brockman MA, Knipe DM.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112327
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Cryopreserved Cell Monolayers for Rapid Detection of Herpes Simplex Virus and Influenza Virus. by Huang YT, Yan H, Sun Y, Jollick, Jr. JA, Baird H.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139648
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Cytokine-Mediated Survival from Lethal Herpes Simplex Virus Infection: Role of Programmed Neuronal Death. by Geiger KD, Gurushanthaiah D, Howes EL, Lewandowski GA, Reed JC, Bloom FE, Sarvetnick NE.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42176
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Cytoplasmic Domain of Herpes Simplex Virus gE Causes Accumulation in the transGolgi Network, a Site of Virus Envelopment and Sorting of Virions to Cell Junctions. by McMillan TN, Johnson DC.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115139
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Dendrimers, a New Class of Candidate Topical Microbicides with Activity against Herpes Simplex Virus Infection. by Bourne N, Stanberry LR, Kern ER, Holan G, Matthews B, Bernstein DI.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90087
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Detection and Direct Typing of Herpes Simplex Virus in Perianal Ulcers of Patients with AIDS by PCR. by do Nascimento MC, Sumita LM, de Souza VA, Pannuti CS.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104644
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Detection of a transforming fragment of herpes simplex virus type 2 in clinical specimens by PCR. The Canadian Women's HIV Study Group. by Guibinga GH, Coutlee F, Kessous A, Hankins C, Lapointe N, Richer G, Tousignant J.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229089
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Detection of Herpes Simplex Virus DNA by Real-Time PCR. by Kessler HH, Muhlbauer G, Rinner B, Stelzl E, Berger A, Dorr HW, Santner B, Marth E, Rabenau H.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86985
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Detection of Herpes Simplex Virus DNA in Genital and Dermal Specimens by LightCycler PCR after Extraction using the IsoQuick, MagNA Pure, and BioRobot 9604 Methods. by Espy MJ, Rys PN, Wold AD, Uhl JR, Sloan LM, Jenkins GD, Ilstrup DM, Cockerill FR III, Patel R, Rosenblatt JE, Smith TF.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88116
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Detection of herpes simplex virus type 1 latency-associated transcript expression in trigeminal ganglia by in situ reverse transcriptase PCR. by Ramakrishnan R, Poliani PL, Levine M, Glorioso JC, Fink DJ.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190691
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Detection of Herpes Simplex Virus Type 2-Specific Immunoglobulin G Antibodies in African Sera by Using Recombinant gG2, Western Blotting, and gG2 Inhibition. by Hogrefe W, Su X, Song J, Ashley R, Kong L.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130895
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Detection of JC Virus in Cerebrospinal Fluid (CSF) Samples from Patients with Progressive Multifocal Leukoencephalopathy but Not in CSF Samples from Patients with Herpes Simplex Encephalitis, Enteroviral Meningitis, or Multiple Sclerosis. by Bogdanovic G, Priftakis P, Hammarin AL, Soderstrom M, Samuelson A, LewensohnFuchs I, Dalianis T.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104707
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Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes. by Diaz-Mitoma F, Ruben M, Sacks S, MacPherson P, Caissie G.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228865
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Development and Optimization of Herpes Simplex Virus Vectors for Multiple LongTerm Gene Delivery to the Peripheral Nervous System. by Palmer JA, Branston RH, Lilley CE, Robinson MJ, Groutsi F, Smith J, Latchman DS, Coffin RS.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112048
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Development of a High-Throughput Quantitative Assay for Detecting Herpes Simplex Virus DNA in Clinical Samples. by Ryncarz AJ, Goddard J, Wald A, Huang ML, Roizman B, Corey L.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84990
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Diagnosis of Herpes Simplex Virus Infections in the Clinical Laboratory by LightCycler PCR. by Espy MJ, Uhl JR, Mitchell PS, Thorvilson JN, Svien KA, Wold AD, Smith TF.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86206
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Dichotomy of Glycoprotein G Gene in Herpes Simplex Virus Type 1 Isolates. by Rekabdar E, Tunback P, Liljeqvist JA, Lindh M, Bergstrom T.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130675
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Difference in Incidence of Spontaneous Mutations between Herpes Simplex Virus Types 1 and 2. by Sarisky RT, Nguyen TT, Duffy KE, Wittrock RJ, Leary JJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89907
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Differentiation of primary from nonprimary genital herpes infections by a herpes simplex virus-specific immunoglobulin G avidity assay. by Hashido M, Inouye S, Kawana T.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229837
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Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis. by Aguilar JS, Roy D, Ghazal P, Wagner EK.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116584
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Disruption of Virion Host Shutoff Activity Improves the Immunogenicity and Protective Capacity of a Replication-Incompetent Herpes Simplex Virus Type 1 Vaccine Strain. by Geiss BJ, Smith TJ, Leib DA, Morrison LA.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113198
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Disseminated Herpes Simplex Virus and Varicella Zoster Virus Coinfection in a Patient Taking Thalidomide for Relapsed Multiple Myeloma. by Curley MJ, Hussein SA, Hassoun PM.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130681
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DNA Immunization against Herpes Simplex Virus: Enhanced Efficacy Using a Sindbis Virus-Based Vector. by Hariharan MJ, Driver DA, Townsend K, Brumm D, Polo JM, Belli BA, Catton DJ, Hsu D, Mittelstaedt D, McCormack JE, Karavodin L, Dubensky TW Jr, Chang SM, Banks TA.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124565
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DNA Vaccines Encoding Interleukin-8 and RANTES Enhance Antigen-Specific Th1Type CD4 + T-Cell-Mediated Protective Immunity against Herpes Simplex Virus Type 2 In Vivo. by Sin JI, Kim JJ, Pachuk C, Satishchandran C, Weiner DB.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113206
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Double-Blind, Randomized, Placebo-Controlled Study of Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) for Treatment of UV Radiation-Induced Herpes Labialis. by Evans TG, Bernstein DI, Raborn GW, Harmenberg J, Kowalski J, Spruance SL.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127265
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Downstream regulatory elements increase acute and latent herpes simplex virus type 2 latency-associated transcript expression but do not influence recurrence phenotype or establishment of latency. by Yoshikawa T, Stanberry LR, Bourne N, Krause PR.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189975
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Effect of Famciclovir on Herpes Simplex Virus Type 1 Corneal Disease and Establishment of Latency in Rabbits. by Loutsch JM, Sainz B Jr, Marquart ME, Zheng X, Kesavan P, Higaki S, Hill JM, Tal-Singer R.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90598
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Effect of foscarnet cream on experimental UV radiation-induced herpes labialis. by Bernstein DI, Schleupner CJ, Evans TG, Blumberg DA, Bryson Y, Grafford K, Broberg P, Martin-Munley S, Spruance SL.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164045
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Effects of Antiviral Usage on Transmission Dynamics of Herpes Simplex Virus Type 1 and on Antiviral Resistance: Predictions of Mathematical Models. by Lipsitch M, Bacon TH, Leary JJ, Antia R, Levin BR.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90157
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Effects of Herpes Simplex Virus on Structure and Function of Nectin-1/HveC. by Krummenacher C, Baribaud I, Sanzo JF, Cohen GH, Eisenberg RJ.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153823
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Effects of Mutations within the Herpes Simplex Virus Type 1 DNA Encapsidation Signal on Packaging Efficiency. by Hodge PD, Stow ND.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114466
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Effects of Targeting Herpes Simplex Virus Type 1 gD to the Endoplasmic Reticulum and trans-Golgi Network. by Whiteley A, Bruun B, Minson T, Browne H.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112986
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Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1. by Piret J, Lamontagne J, Desormeaux A, Bergeron MG.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90421
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Efficacies of Topical Formulations of Foscarnet and Acyclovir and of 5-Percent Acyclovir Ointment (Zovirax) in a Murine Model of Cutaneous Herpes Simplex Virus Type 1 Infection. by Piret J, Desormeaux A, Gourde P, Juhasz J, Bergeron MG.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89624
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Efficient Activation of Viral Genomes by Levels of Herpes Simplex Virus ICP0 Insufficient To Affect Cellular Gene Expression or Cell Survival. by Hobbs WE, Brough DE, Kovesdi I, DeLuca NA.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114132
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Enhancer and Long-Term Expression Functions of Herpes Simplex Virus Type 1 Latency-Associated Promoter Are both Located in the Same Region. by Berthomme H, Thomas J, Texier P, Epstein A, Feldman LT.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114183
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Equine Herpesvirus 1 Gene 12 Can Substitute for vmw65 in the Growth of Herpes Simplex Virus (HSV) Type 1, Allowing the Generation of Optimized Cell Lines for the Propagation of HSV Vectors with Multiple Immediate-Early Gene Defects. by Thomas SK, Lilley CE, Latchman DS, Coffin RS.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104267
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Evaluation of a Novel, Anti-Herpes Simplex Virus Compound, Acyclovir Elaidate (P4010), in the Female Guinea Pig Model of Genital Herpes. by Jennings R, Smith TL, Myhren F, Phillips J, Sandvold ML.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89020
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Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease. by Brandt CR, Spencer B, Imesch P, Garneau M, Deziel R.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163269
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Evaluation of a quantitative competitive PCR assay for measuring herpes simplex virus DNA content in genital tract secretions. by Hobson A, Wald A, Wright N, Corey L.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229624
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Evaluation of Confirmatory Strategies for Detection of Type-Specific Antibodies against Herpes Simplex Virus Type 2. by Eing BR, Lippelt L, Lorentzen EU, Hafezi W, Schlumberger W, Steinhagen K, Kuhn JE.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153348
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Evaluation of LightCycler PCR for Implementation of Laboratory Diagnosis of Herpes Simplex Virus Infections. by Espy MJ, Ross TK, Teo R, Svien KA, Wold AD, Uhl JR, Smith TF.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87205
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Evaluation of Three Glycoprotein G2-Based Enzyme Immunoassays for Detection of Antibodies to Herpes Simplex Virus Type 2 in Human Sera. by Eis-Hubinger AM, Daumer M, Matz B, Schneweis KE.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84740
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Evidence for a Bidirectional Element Located Downstream from the Herpes Simplex Virus Type 1 Latency-Associated Promoter That Increases Its Activity during Latency. by Berthomme H, Lokensgard J, Yang L, Margolis T, Feldman LT.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111871
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Evidence for Controlled Incorporation of Herpes Simplex Virus Type 1 UL26 Protease into Capsids. by Sheaffer AK, Newcomb WW, Brown JC, Gao M, Weller SK, Tenney DJ.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112201
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Evidence that Herpes Simplex Virus VP16 Is Required for Viral Egress Downstream of the Initial Envelopment Event. by Mossman KL, Sherburne R, Lavery C, Duncan J, Smiley JR.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112134
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Evidence that two latency-associated transcripts of herpes simplex virus type 1 are nonlinear. by Wu TT, Su YH, Block TM, Taylor JM.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190616
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Examination of the Kinetics of Herpes Simplex Virus Glycoprotein D Binding to the Herpesvirus Entry Mediator, Using Surface Plasmon Resonance. by Willis SH, Rux AH, Peng C, Whitbeck JC, Nicola AV, Lou H, Hou W, Salvador L, Eisenberg RJ, Cohen GH.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110398
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Experimental investigation of herpes simplex virus latency. by Wagner EK, Bloom DC.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172928
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Explant-Induced Reactivation of Herpes Simplex Virus Occurs in Neurons Expressing Nuclear cdk2 and cdk4. by Schang LM, Bantly A, Schaffer PA.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136347
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Expression of Herpes Simplex Virus ICP0 Inhibits the Induction of InterferonStimulated Genes by Viral Infection. by Eidson KM, Hobbs WE, Manning BJ, Carlson P, DeLuca NA.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153810
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Famciclovir and Valaciclovir Differ in the Prevention of Herpes Simplex Virus Type 1 Latency in Mice: a Quantitative Study. by Thackray AM, Field HJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105644
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Flow cytometric analysis of herpes simplex virus type 1 susceptibility to acyclovir, ganciclovir, and foscarnet. by Pavic I, Hartmann A, Zimmermann A, Michel D, Hampl W, Schleyer I, Mertens T.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164189
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Fluorescent Tagging of Herpes Simplex Virus Tegument Protein VP13/14 in Virus Infection. by Donnelly M, Elliott G.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115880
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Frequency of Acyclovir-Resistant Herpes Simplex Virus in Clinical Specimens and Laboratory Isolates. by Shin YK, Cai GY, Weinberg A, Leary JJ, Levin MJ.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87849
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Function of Dynein and Dynactin in Herpes Simplex Virus Capsid Transport. by Dohner K, Wolfstein A, Prank U, Echeverri C, Dujardin D, Vallee R, Sodeik B.; 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117943
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Functional Anatomy of Herpes Simplex Virus 1 Overlapping Genes Encoding Infected-Cell Protein 22 and US1.5 Protein. by Ogle WO, Roizman B.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104212
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Functional Interaction between Fluorodeoxyuridine-Induced Cellular Alterations and Replication of a Ribonucleotide Reductase-Negative Herpes Simplex Virus. by Petrowsky H, Roberts GD, Kooby DA, Burt BM, Bennett JJ, Delman KA, Stanziale SF, Delohery TM, Tong WP, Federoff HJ, Fong Y.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114433
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Functional Region IV of Glycoprotein D from Herpes Simplex Virus Modulates Glycoprotein Binding to the Herpesvirus Entry Mediator. by Rux AH, Willis SH, Nicola AV, Hou W, Peng C, Lou H, Cohen GH, Eisenberg RJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109930
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Gamma Interferon (IFN-[gamma]) Receptor Null-Mutant Mice Are More Susceptible to Herpes Simplex Virus Type 1 Infection than IFN-[gamma] Ligand Null-Mutant Mice. by Cantin E, Tanamachi B, Openshaw H, Mann J, Clarke K.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112570
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Gamma Interferon Can Prevent Herpes Simplex Virus Type 1 Reactivation from Latency in Sensory Neurons. by Liu T, Khanna KM, Carriere BN, Hendricks RL.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114697
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Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. by Cantin EM, Hinton DR, Chen J, Openshaw H.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189304
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Gender Influences Herpes Simplex Virus Type 1 Infection in Normal and Gamma Interferon-Mutant Mice. by Han X, Lundberg P, Tanamachi B, Openshaw H, Longmate J, Cantin E.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115935
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Gene Array Analysis Reveals Changes in Peripheral Nervous System Gene Expression following Stimuli That Result in Reactivation of Latent Herpes Simplex Virus Type 1: Induction of Transcription Factor Bcl-3. by Tsavachidou D, Podrzucki W, Seykora J, Berger SL.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114562
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Genetic Analysis of the Role of Herpes Simplex Virus Type 1 Glycoprotein K in Infectious Virus Production and Egress. by Foster TP, Kousoulas KG.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112865
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Genetic Studies Exposing the Splicing Events Involved in Herpes Simplex Virus Type 1 Latency-Associated Transcript Production during Lytic and Latent Infection. by Alvira MR, Goins WF, Cohen JB, Glorioso JC.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104164
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Genital herpes. by Oakeshott P, Hay P.; 2002 May 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104337
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Genital Herpes: Review of the Epidemic and Potential Use of Type-Specific Serology. by Ashley RL, Wald A.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88903
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Global Analysis of Herpes Simplex Virus Type 1 Transcription Using an Oligonucleotide-Based DNA Microarray. by Stingley SW, Ramirez JJ, Aguilar SA, Simmen K, Sandri-Goldin RM, Ghazal P, Wagner EK.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102029
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Glycoprotein D or J Delivered in trans Blocks Apoptosis in SK-N-SH Cells Induced by a Herpes Simplex Virus 1 Mutant Lacking Intact Genes Expressing Both Glycoproteins. by Zhou G, Galvan V, Campadelli-Fiume G, Roizman B.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112461
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Glycoprotein K Specified by Herpes Simplex Virus Type 1 Is Expressed on Virions as a Golgi Complex-Dependent Glycosylated Species and Functions in Virion Entry. by Foster TP, Rybachuk GV, Kousoulas KG.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116139
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Granzyme A, a Noncytolytic Component of CD8 + Cell Granules, Restricts the Spread of Herpes Simplex Virus in the Peripheral Nervous Systems of Experimentally Infected Mice. by Pereira RA, Simon MM, Simmons A.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111627
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Heparan Sulfate Proteoglycan Binding by Herpes Simplex Virus Type 1 Glycoproteins B and C, Which Differ in Their Contributions to Virus Attachment, Penetration, and Cell-to-Cell Spread. by Laquerre S, Argnani R, Anderson DB, Zucchini S, Manservigi R, Glorioso JC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110418
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Herpes simplex virus 1 activates cdc2 to recruit topoisomerase II[alpha] for post-DNA synthesis expression of late genes. by Advani SJ, Weichselbaum RR, Roizman B.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153640
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Herpes Simplex Virus 1 Blocks Caspase-3-Independent and Caspase-Dependent Pathways to Cell Death. by Galvan V, Brandimarti R, Roizman B.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104085
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Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. by Galvan V, Roizman B.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19940
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Herpes Simplex Virus 1 Open Reading Frames O and P Are Not Necessary for Establishment of Latent Infection in Mice. by Randall G, Lagunoff M, Roizman B.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102098
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Herpes Simplex Virus 1 Regulatory Protein ICP22 Interacts with a New Cell CycleRegulated Factor and Accumulates in a Cell Cycle-Dependent Fashion in Infected Cells. by Bruni R, Roizman B.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110262
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Herpes Simplex Virus DNA Cleavage and Packaging Proteins Associate with the Procapsid prior to Its Maturation. by Sheaffer AK, Newcomb WW, Gao M, Yu D, Weller SK, Brown JC, Tenney DJ.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113965
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Herpes Simplex Virus DNA Cleavage and Packaging: Association of Multiple Forms of UL15-Encoded Proteins with B Capsids Requires at Least the UL6, UL17, and UL28 Genes. by Salmon B, Baines JD.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109752
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Herpes Simplex Virus DNA Packaging without Measurable DNA Synthesis. by Church GA, Dasgupta A, Wilson DW.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109718
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Herpes Simplex Virus gD and Virions Accumulate in Endosomes by Mannose 6Phosphate-Dependent and -Independent Mechanisms. by Brunetti CR, Dingwell KS, Wale C, Graham FL, Johnson DC.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109812
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Herpes Simplex Virus gE/gI Sorts Nascent Virions to Epithelial Cell Junctions, Promoting Virus Spread. by Johnson DC, Webb M, Wisner TW, Brunetti C.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113978
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Herpes simplex virus gene expression in neurons: viral DNA synthesis is a critical regulatory event in the branch point between the lytic and latent pathways. by Nichol PF, Chang JY, Johnson EM Jr, Olivo PD.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190505
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Herpes Simplex Virus Genome Isomerization: Origins of Adjacent Long Segments in Concatemeric Viral DNA. by Slobedman B, Zhang X, Simmons A.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103895
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Herpes Simplex Virus Glycoprotein D Can Bind to Poliovirus Receptor-Related Protein 1 or Herpesvirus Entry Mediator, Two Structurally Unrelated Mediators of Virus Entry. by Krummenacher C, Nicola AV, Whitbeck JC, Lou H, Hou W, Lambris JD, Geraghty RJ, Spear PG, Cohen GH, Eisenberg RJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109927
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Herpes Simplex Virus ICP0 and ICP34.5 Counteract Distinct Interferon-Induced Barriers to Virus Replication. by Mossman KL, Smiley JR.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135894
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Herpes Simplex Virus ICP0 Mutants Are Hypersensitive to Interferon. by Mossman KL, Saffran HA, Smiley JR.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111685
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Herpes Simplex Virus ICP27 Induces Cytoplasmic Accumulation of Unspliced Polyadenylated [alpha]-Globin Pre-mRNA in Infected HeLa Cells. by Cheung P, Ellison KS, Verity R, Smiley JR.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111785
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Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway. by Koffa MD, Clements JB, Izaurralde E, Wadd S, Wilson SA, Mattaj IW, Kuersten S.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125682
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Herpes Simplex Virus IE63 (ICP27) Protein Interacts with Spliceosome-Associated Protein 145 and Inhibits Splicing prior to the First Catalytic Step. by Bryant HE, Wadd SE, Lamond AI, Silverstein SJ, Clements JB.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114182
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Herpes Simplex Virus Infected Cell Polypeptide 4 Preferentially Represses Sp1Activated Over Basal Transcription from Its Own Promoter. by Gu B, Rivera-Gonzalez R, Smith CA, DeLuca NA.; 1993 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47602
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Herpes Simplex Virus Infections of Women and Their Offspring: Implications for a Developed Society. by Whitley RJ.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43386
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Herpes Simplex Virus Latency-Associated Transcript Encodes a Protein Which Greatly Enhances Virus Growth, Can Compensate for Deficiencies in ImmediateEarly Gene Expression, and Is Likely To Function during Reactivation from Virus Latency. by Thomas SK, Gough G, Latchman DS, R. S. , Coffin.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112746
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Herpes Simplex Virus Nucleocapsids Mature to Progeny Virions by an Envelopment [right arrow] Deenvelopment [right arrow] Reenvelopment Pathway. by Skepper JN, Whiteley A, Browne H, Minson A.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114284
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Herpes Simplex Virus Processivity Factor UL42 Imparts Increased DNA-Binding Specificity to the Viral DNA Polymerase and Decreased Dissociation from Primer-
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Template without Reducing the Elongation Rate. by Weisshart K, Chow CS, Coen DM.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103808 •
Herpes Simplex Virus Selectively Induces Expression of the CC Chemokine RANTES/CCL5 in Macrophages through a Mechanism Dependent on PKR and ICP0. by Melchjorsen J, Pedersen FS, Mogensen SC, Paludan SR.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135968
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Herpes Simplex Virus Triggers and Then Disarms a Host Antiviral Response. by Mossman KL, Macgregor PF, Rozmus JJ, Goryachev AB, Edwards AM, Smiley JR.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113971
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Herpes Simplex Virus Type 1 2-Kilobase Latency-Associated Transcript Intron Associates with Ribosomal Proteins and Splicing Factors. by Ahmed M, Fraser NW.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116102
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Herpes Simplex Virus Type 1 Blocks the Apoptotic Host Cell Defense Mechanisms That Target Bcl-2 and Manipulates Activation of p38 Mitogen-Activated Protein Kinase To Improve Viral Replication. by Zachos G, Koffa M, Preston CM, Clements JB, Conner J.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115896
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Herpes Simplex Virus Type 1 Cleavage and Packaging Proteins UL15 and UL28 Are Associated with B but Not C Capsids during Packaging. by Yu D, Weller SK.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109972
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Herpes Simplex Virus Type 1 Corneal Infection Results in Periocular Disease by Zosteriform Spread. by Summers BC, Margolis TP, Leib DA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114911
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Herpes Simplex Virus Type 1 Entry into Host Cells: Reconstitution of Capsid Binding and Uncoating at the Nuclear Pore Complex In Vitro. by Ojala PM, Sodeik B, Ebersold MW, Kutay U, Helenius A.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85943
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Herpes Simplex Virus Type 1 Entry Is Inhibited by the Cobalt Chelate Complex CTC96. by Schwartz JA, Lium EK, Silverstein SJ.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114157
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Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo. by Lubinski JM, Jiang M, Hook L, Chang Y, Sarver C, Mastellos D, Lambris JD, Cohen GH, Eisenberg RJ, Friedman HM.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136467
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Herpes Simplex Virus Type 1 Gene UL14: Phenotype of a Null Mutant and Identification of the Encoded Protein. by Cunningham C, Davison AJ, MacLean AR, Taus NS, Baines JD.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111510
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Herpes Simplex Virus Type 1 Glycoprotein B Requires a Cysteine Residue at Position 633 for Folding, Processing, and Incorporation into Mature Infectious Virus Particles. by Laquerre S, Anderson DB, Argnani R, Glorioso JC.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110055
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Herpes Simplex Virus Type 1 Glycoprotein E Domains Involved in Virus Spread and Disease. by Saldanha CE, Lubinski J, Martin C, Nagashunmugam T, Wang L, van der Keyl H, Tal-Singer R, Friedman HM.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112186
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Herpes Simplex Virus Type 1 Glycoprotein gC Mediates Immune Evasion In Vivo. by Lubinski JM, Wang L, Soulika AM, Burger R, Wetsel RA, Colten H, Cohen GH, Eisenberg RJ, Lambris JD, Friedman HM.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110183
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Herpes Simplex Virus Type 1 ICP0 Protein Does Not Accumulate in the Nucleus of Primary Neurons in Culture. by Chen XP, Li J, Mata M, Goss J, Wolfe D, Glorioso JC, Fink DJ.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102052
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Herpes Simplex Virus Type 1 ICP4 Promotes Transcription Preinitiation Complex Formation by Enhancing the Binding of TFIID to DNA. by Grondin B, DeLuca N.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112430
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Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 Induces the Proteasome-Dependent Degradation of the Catalytic Subunit of DNA-Dependent Protein Kinase. by Parkinson J, Lees-Miller SP, Everett RD.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103871
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Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 Inhibits Progression of Cells through Mitosis and from G1 into S Phase of the Cell Cycle. by Lomonte P, Everett RD.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112980
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Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene Promotes Neuronal Survival. by Thompson RL, Sawtell NM.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114389
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Herpes Simplex Virus Type 1 Latency-Associated Transcripts Suppress Viral Replication and Reduce Immediate-Early Gene mRNA Levels in a Neuronal Cell Line. by Mador N, Goldenberg D, Cohen O, Panet A, Steiner I.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110070
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Herpes Simplex Virus Type 1 Origins of DNA Replication Play No Role in the Regulation of Flanking Promoters. by Summers BC, Leib DA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136320
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Herpes Simplex Virus Type 1 Promoter Activity during Latency Establishment, Maintenance, and Reactivation in Primary Dorsal Root Neurons In Vitro. by Arthur JL, Scarpini CG, Connor V, Lachmann RH, Tolkovsky AM, Efstathiou S.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114879
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Herpes simplex virus type 1 protein IE63 affects the nuclear export of virus introncontaining transcripts. by Phelan A, Dunlop J, Clements JB.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190482
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Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic TLymphocyte-Induced Apoptosis. by Jerome KR, Tait JF, Koelle DM, Corey L.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109392
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Herpes Simplex Virus Type 1 Serum Neutralizing Antibody Titers Increase during Latency in Rabbits Latently Infected with Latency-Associated Transcript (LAT)-
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Positive but Not LAT-Negative Viruses. by Perng GC, Slanina SM, Yukht A, Ghiasi H, Nesburn AB, Wechsler SL.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113008 •
Herpes Simplex Virus Type 1 UL34 Gene Product Is Required for Viral Envelopment. by Roller RJ, Zhou Y, Schnetzer R, Ferguson J, DeSalvo D.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111520
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Herpes Simplex Virus Type 1 Vector-Mediated Expression of Nerve Growth Factor Protects Dorsal Root Ganglion Neurons from Peroxide Toxicity. by Goins WF, Lee KA, Cavalcoli JD, O'Malley ME, DeKosky ST, Fink DJ, Glorioso JC.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103859
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Herpes Simplex Virus Type 1-Specific Cytotoxic T-Lymphocyte Arming Occurs within Lymph Nodes Draining the Site of Cutaneous Infection. by Jones CM, Cose SC, Coles RM, Winterhalter AC, Brooks AG, Heath WR, Carbone FR.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111723
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Herpes Simplex Virus Type 2 Glycoprotein G-Negative Clinical Isolates Are Generated by Single Frameshift Mutations. by Liljeqvist JA, Svennerholm B, Bergstrom T.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113027
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Herpes Simplex Virus Types 1 and 2 Differ in Their Interaction with Heparan Sulfate. by Trybala E, Liljeqvist JA, Svennerholm B, Bergstrom T.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102109
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Herpes Simplex Virus Vectors Elicit Durable Immune Responses in the Presence of Preexisting Host Immunity. by Brockman MA, Knipe DM.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136066
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Herpes Simplex Virus Virion Host Shutoff (vhs) Activity Alters Periocular Disease in Mice. by Smith TJ, Ackland-Berglund CE, Leib DA.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111869
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Herpes Simplex Virus Virion Host Shutoff Protein Requires a Mammalian Factor for Efficient In Vitro Endoribonuclease Activity. by Lu P, Jones FE, Saffran HA, Smiley JR.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114023
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Herpes Simplex Virus with Highly Reduced gD Levels Can Efficiently Enter and Spread between Human Keratinocytes. by Huber MT, Wisner TW, Hegde NR, Goldsmith KA, Rauch DA, Roller RJ, Krummenacher C, Eisenberg RJ, Cohen GH, Johnson DC.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114605
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Herpes simplex viruses: is a vaccine tenable? by Whitley RJ, Roizman B.; 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151069
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Herpes Simplex Virus-Induced Keratitis: Evaluation of the Role of Molecular Mimicry in Lesion Pathogenesis. by Deshpande SP, Lee S, Zheng M, Song B, Knipe D, Kapp JA, Rouse BT.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114101
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High frequency of CD8+ cytotoxic T-lymphocyte precursors specific for herpes simplex viruses in persons with genital herpes. by Posavad CM, Koelle DM, Corey L.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190896
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High-dose ocular infection with a herpes simplex virus type 1 ICP34.5 deletion mutant produces no corneal disease or neurovirulence yet results in wild-type levels of spontaneous reactivation. by Perng GC, Ghiasi H, Slanina SM, Nesburn AB, Wechsler SL.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190146
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Highly Reliable Heterologous System for Evaluating Resistance of Clinical Herpes Simplex Virus Isolates to Nucleoside Analogues. by Bestman-Smith J, Schmit I, Papadopoulou B, Boivin G.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114104
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Human Corneal Cells and Other Fibroblasts Can Stimulate the Appearance of Herpes Simplex Virus from Quiescently Infected PC12 Cells. by Su YH, Meegalla RL, Chowhan R, Cubitt C, Oakes JE, Lausch RN, Fraser NW, Block TM.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104196
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Human Immunodeficiency Virus tat Gene Transfer to the Murine Central Nervous System Using a Replication-Defective Herpes Simplex Virus Vector Stimulates Transforming Growth Factor Beta 1 Gene Expression. by Rasty S, Thatikunta P, Gordon J, Khalili K, Amini S, Glorioso JC.; 1996 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39191
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Human Neuron-Committed Teratocarcinoma NT2 Cell Line Has Abnormal ND10 Structures and Is Poorly Infected by Herpes Simplex Virus Type 1. by Hsu WL, Everett RD.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114873
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Human Thymidine Kinase Can Functionally Replace Herpes Simplex Virus Type 1 Thymidine Kinase for Viral Replication in Mouse Sensory Ganglia and Reactivation from Latency upon Explant. by Chen SH, Cook WJ, Grove KL, Coen DM.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109874
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Humoral response to herpes simplex virus is complement-dependent. by Da Costa XJ, Brockman MA, Alicot E, Ma M, Fischer MB, Zhou X, Knipe DM, Carroll MC.; 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23060
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HveA (Herpesvirus Entry Mediator A), a Coreceptor for Herpes Simplex Virus Entry, also Participates in Virus-Induced Cell Fusion. by Terry-Allison T, Montgomery RI, Whitbeck JC, Xu R, Cohen GH, Eisenberg RJ, Spear PG.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110382
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ICP0 Is Required for Efficient Reactivation of Herpes Simplex Virus Type 1 from Neuronal Latency. by Halford WP, Schaffer PA.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114117
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ICP0, ICP4, or VP16 Expressed from Adenovirus Vectors Induces Reactivation of Latent Herpes Simplex Virus Type 1 in Primary Cultures of Latently Infected Trigeminal Ganglion Cells. by Halford WP, Kemp CD, Isler JA, Davido DJ, Schaffer PA.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114330
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ICP22 and the UL13 Protein Kinase Are both Required for Herpes Simplex VirusInduced Modification of the Large Subunit of RNA Polymerase II. by Long MC, Leong V, Schaffer PA, Spencer CA, Rice SA.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112617
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Identification of a Region of the Herpes Simplex Virus Single-Stranded DNABinding Protein Involved in Cooperative Binding. by Dudas KC, Ruyechan WT.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109371
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Identification of an Export Control Sequence and a Requirement for the KH Domains in ICP27 from Herpes Simplex Virus Type 1. by Soliman TM, Silverstein SJ.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112281
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Identification of Crucial Hydrogen-Bonding Residues for the Interaction of Herpes Simplex Virus DNA Polymerase Subunits via Peptide Display, Mutational, and Calorimetric Approaches. by Bridges KG, Chow CS, Coen DM.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114902
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Identification of Herpes Simplex Virus Type 1 Latency-Associated Transcript Sequences That both Inhibit Apoptosis and Enhance the Spontaneous Reactivation Phenotype. by Jin L, Peng W, Perng GC, Brick DJ, Nesburn AB, Jones C, Wechsler SL.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155006
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Immature Monocyte-Derived Dendritic Cells Are Productively Infected with Herpes Simplex Virus Type 1. by Mikloska Z, Bosnjak L, Cunningham AL.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114311
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Immunization against genital herpes with a vaccine virus that has defects in productive and latent infection. by Da Costa XJ, Jones CA, Knipe DM.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22033
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Immunization with a replication-deficient mutant of herpes simplex virus type 1 (HSV-1) induces a CD8+ cytotoxic T-lymphocyte response and confers a level of protection comparable to that of wild-type HSV-1. by Brehm MA, Bonneau RH, Knipe DM, Tevethia SS.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191500
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Immunization with a Single Major Histocompatibility Complex Class I-Restricted Cytotoxic T-Lymphocyte Recognition Epitope of Herpes Simplex Virus Type 2 Confers Protective Immunity. by Blaney JE Jr, Nobusawa E, Brehm MA, Bonneau RH, Mylin LM, Fu TM, Kawaoka Y, Tevethia SS.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110466
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Immunization with Chaperone-Peptide Complex Induces Low-Avidity Cytotoxic T Lymphocytes Providing Transient Protection against Herpes Simplex Virus Infection. by Kumaraguru U, Gierynska M, Norman S, Bruce BD, Rouse BT.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135705
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Immunization with DNA Vaccines Encoding Glycoprotein D or Glycoprotein B, Alone or in Combination, Induces Protective Immunity in Animal Models of Herpes Simplex Virus-2 Disease. by McClements WL, Armstrong ME, Keys RD, Liu MA.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38071
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Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs. by Heineman TC, Connelly BL, Bourne N, Stanberry LR, Cohen J.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189763
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Immunoglobulin G is the main protective antibody in mouse vaginal secretions after vaginal immunization with attenuated herpes simplex virus type 2. by Parr EL, Parr MB.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192266
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Immunohistochemical Analysis of Primary Sensory Neurons Latently Infected with Herpes Simplex Virus Type 1. by Yang L, Voytek CC, Margolis TP.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111530
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In Vitro Processing of Herpes Simplex Virus Type 1 DNA Replication Intermediates by the Viral Alkaline Nuclease, UL12. by Goldstein JN, Weller SK.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110293
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In vivo epinephrine reactivation of ocular herpes simplex virus type 1 in the rabbit is correlated to a 370-base-pair region located between the promoter and the 5' end of the 2.0 kilobase latency-associated transcript. by Hill JM, Maggioncalda JB, Garza HH Jr, Su YH, Fraser NW, Block TM.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190787
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In Vivo Immune Evasion Mediated by the Herpes Simplex Virus Type 1 Immunoglobulin G Fc Receptor. by Nagashunmugam T, Lubinski J, Wang L, Goldstein LT, Weeks BS, Sundaresan P, Kang EH, Dubin G, Friedman HM.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110157
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In Vivo Modulation of Vaccine-Induced Immune Responses toward a Th1 Phenotype Increases Potency and Vaccine Effectiveness in a Herpes Simplex Virus Type 2 Mouse Model. by Sin JI, Kim JJ, Boyer JD, Ciccarelli RB, Higgins TJ, Weiner DB.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103857
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Induction and Prevention of Apoptosis in Human HEp-2 Cells by Herpes Simplex Virus Type 1. by Aubert M, O'Toole J, Blaho JA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113091
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Induction of CD8 T-Cell-Specific Systemic and Mucosal Immunity against Herpes Simplex Virus with CpG-Peptide Complexes. by Gierynska M, Kumaraguru U, Eo SK, Lee S, Krieg A, Rouse BT.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136257
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Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization. by Kuklin N, Daheshia M, Karem K, Manickan E, Rouse BT.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191446
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Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection. by Liu T, Tang Q, Hendricks RL.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189813
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Inhibition by Interferon of Herpes Simplex Virus Type 1-Activated Transcription of tat-Defective Provirus. by Popik W, Pitha PM.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52760
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Inhibition of Herpes Simplex Virus Replication by a 2-Amino Thiazole via Interactions with the Helicase Component of the UL5-UL8-UL52 Complex. by Spector FC, Liang L, Giordano H, Sivaraja M, Peterson MG.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109917
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Interaction between Herpes Simplex Virus Type 1 IE63 Protein and Cellular Protein p32. by Bryant HE, Matthews DA, Wadd S, Scott JE, Kean J, Graham S, Russell WC, Clements JB.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113237
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Interactions of Herpes Simplex Virus Type 1 with ND10 and Recruitment of PML to Replication Compartments. by Burkham J, Coen DM, Hwang CB, Weller SK.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114819
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Interference with Major Histocompatibility Complex Class II-Restricted Antigen Presentation in the Brain by Herpes Simplex Virus Type 1: A Possible Mechanism of Evasion of the Immune Response. by Lewandowski GA, Lo D, Bloom FE.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46009
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Interleukin-12 (IL-12) and IL-18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity. by Harandi AM, Svennerholm B, Holmgren J, Eriksson K.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114395
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Interleukin-12- and Gamma Interferon-Dependent Innate Immunity Are Essential and Sufficient for Long-Term Survival of Passively Immunized Mice Infected with Herpes Simplex Virus Type 1. by Vollstedt S, Franchini M, Alber G, Ackermann M, Suter M.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114530
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Interleukin-18 Protects Mice against Acute Herpes Simplex Virus Type 1 Infection. by Fujioka N, Akazawa R, Ohashi K, Fujii M, Ikeda M, Kurimoto M.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104486
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Intracellular Cre-Mediated Deletion of the Unique Packaging Signal Carried by a Herpes Simplex Virus Type 1 Recombinant and Its Relationship to the CleavagePackaging Process. by Logvinoff C, Epstein AL.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116351
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Intrastrain Variants of Herpes Simplex Virus Type 1 Isolated from a Neonate with Fatal Disseminated Infection Differ in the ICP34.5 Gene, Glycoprotein Processing, and Neuroinvasiveness. by Bower JR, Mao H, Durishin C, Rozenbom E, Detwiler M, Rempinski D, Karban TL, Rosenthal KS.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104162
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Intravenous Penciclovir for Treatment of Herpes Simplex Infections in Immunocompromised Patients: Results of a Multicenter, Acyclovir-Controlled Trial. by Lazarus HM, Belanger R, Candoni A, Aoun M, Jurewicz R, Marks L.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89132
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Herpes Simplex
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Involvement of Apolipoprotein E in the Hematogenous Route of Herpes Simplex Virus Type 1 to the Central Nervous System. by Burgos JS, Ramirez C, Sastre I, Bullido MJ, Valdivieso F.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136918
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Isolation of Herpes Simplex Virus Procapsids from Cells Infected with a ProteaseDeficient Mutant Virus. by Newcomb WW, Trus BL, Cheng N, Steven AC, Sheaffer AK, Tenney DJ, Weller SK, Brown JC.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111641
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Isomerization of a Uniquely Designed Amplicon during Herpes Simplex VirusMediated Replication. by Wang H, Fu X, Zhang X.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114627
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Laboratory diagnosis of central nervous system infections with herpes simplex virus by PCR performed with cerebrospinal fluid specimens. by Mitchell PS, Espy MJ, Smith TF, Toal DR, Rys PN, Berbari EF, Osmon DR, Persing DH.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230078
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Lack of Interleukin-6 (IL-6) Enhances Susceptibility to Infection but Does Not Alter Latency or Reactivation of Herpes Simplex Virus Type 1 in IL-6 Knockout Mice. by LeBlanc RA, Pesnicak L, Cabral ES, Godleski M, Straus SE.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112831
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Limits in Reliability of Glycoprotein G-Based Type-Specific Serologic Assays for Herpes Simplex Virus Types 1 and 2. by Schmid DS, Brown DR, Nisenbaum R, Burke RL, Alexander D', Ashley R, Pellett PE, Reeves WC.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84313
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Live-Cell Analysis of a Green Fluorescent Protein-Tagged Herpes Simplex Virus Infection. by Elliott G, O'Hare P.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104190
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Local Periocular Vaccination Protects against Eye Disease More Effectively Than Systemic Vaccination following Primary Ocular Herpes Simplex Virus Infection in Rabbits. by Nesburn AB, Slanina S, Burke RL, Ghiasi H, Bahri S, Wechsler SL.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110076
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Localization of a Binding Site for Herpes Simplex Virus Glycoprotein D on Herpesvirus Entry Mediator C by Using Antireceptor Monoclonal Antibodies. by Krummenacher C, Baribaud I, Ponce de Leon M, Whitbeck JC, Lou H, Cohen GH, Eisenberg RJ.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113165
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Localization of a Passively Transferred Human Recombinant Monoclonal Antibody to Herpes Simplex Virus Glycoprotein D to Infected Nerve Fibers and Sensory Neurons In Vivo. by Sanna PP, Deerinck TJ, Ellisman MH.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112904
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Localization of the gD-Binding Region of the Human Herpes Simplex Virus Receptor, HveA. by Whitbeck JC, Connolly SA, Willis SH, Hou W, Krummenacher C, Ponce de Leon M, Lou H, Baribaud I, Eisenberg RJ, Cohen GH.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113910
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Longitudinal study of genital infection by herpes simplex virus type 1 in western Scotland over 15 years. by Scoular A, Norrie J, Gillespie G, Mir N, Carman WF.; 2002 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115212
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Long-Term Transgene Expression in Mice Infected with a Herpes Simplex Virus Type 1 Mutant Severely Impaired for Immediate-Early Gene Expression. by Marshall KR, Lachmann RH, Efstathiou S, Rinaldi A, Preston CM.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111616
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Mandelic Acid Condensation Polymer: Novel Candidate Microbicide for Prevention of Human Immunodeficiency Virus and Herpes Simplex Virus Entry. by Herold BC, Scordi-Bello I, Cheshenko N, Marcellino D, Dzuzelewski M, Francois F, Morin R, Casullo VM, Anderson RA, Chany II C, Waller DP, Zaneveld LJ, Klotman ME.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136750
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Mapping of Genes Involved in Murine Herpes Simplex Virus Keratitis: Identification of Genes and Their Modifiers. by Norose K, Yano A, Zhang XM, Blankenhorn E, Heber-Katz E.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136007
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Mapping of Herpes Simplex Virus 1 Genes with Mutations which Overcome Host Restrictions to Infection. by Brandimarti R, Huang T, Roizman B, Campadelli-Fiume G.; 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44004
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Mechanism of Reduced T-Cell Effector Functions and Class-Switched Antibody Responses to Herpes Simplex Virus Type 2 in the Absence of B7 Costimulation. by Thebeau LG, Morrison LA.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141105
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Mechanisms of herpes simplex virus type 1 reactivation. by Halford WP, Gebhardt BM, Carr DJ.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190459
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Microtubule Reorganization during Herpes Simplex Virus Type 1 Infection Facilitates the Nuclear Localization of VP22, a Major Virion Tegument Protein. by Kotsakis A, Pomeranz LE, Blouin A, Blaho JA.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115115
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Modified FGF4 Signal Peptide Inhibits Entry of Herpes Simplex Virus Type 1. by Bultmann H, Busse JS, Brandt CR.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115887
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Modified VP22 Localizes to the Cell Nucleus during Synchronized Herpes Simplex Virus Type 1 Infection. by Pomeranz LE, Blaho JA.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112762
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Modulation of Immunity against Herpes Simplex Virus Infection via Mucosal Genetic Transfer of Plasmid DNA Encoding Chemokines. by Eo SK, Lee S, Chun S, Rouse BT.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113952
86
Herpes Simplex
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Molecular Approaches To Detecting Herpes Simplex Virus and Enteroviruses in the Central Nervous System. by Smalling TW, Sefers SE, Li H, Tang YW.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120559
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Molecular Diagnosis of Herpes Simplex Virus Infections in the Central Nervous System. by Tang YW, Mitchell PS, Espy MJ, Smith TF, Persing DH.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85100
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Monoclonal Antibodies to Distinct Sites on Herpes Simplex Virus (HSV) Glycoprotein D Block HSV Binding to HVEM. by Nicola AV, Ponce de Leon M, Xu R, Hou W, Whitbeck JC, Krummenacher C, Montgomery RI, Spear PG, Eisenberg RJ, Cohen GH.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109580
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mRNA Degradation by the Virion Host Shutoff (Vhs) Protein of Herpes Simplex Virus: Genetic and Biochemical Evidence that Vhs Is a Nuclease. by Everly, Jr. DN, Feng P, Mian IS, Read GS.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136990
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Mucosal Immunity to Herpes Simplex Virus Type 2 Infection in the Mouse Vagina Is Impaired by In Vivo Depletion of T Lymphocytes. by Parr MB, Parr EL.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109710
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Multiple Immediate-Early Gene-Deficient Herpes Simplex Virus Vectors Allowing Efficient Gene Delivery to Neurons in Culture and Widespread Gene Delivery to the Central Nervous System In Vivo. by Lilley CE, Groutsi F, Han Z, Palmer JA, Anderson PN, Latchman DS, Coffin RS.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114179
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Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread. by Rauch DA, Rodriguez N, Roller RJ.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112422
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Mutations in the 5' end of the herpes simplex virus type 2 latency-associated transcript (LAT) promoter affect LAT expression in vivo but not the rate of spontaneous reactivation of genital herpes. by Wang K, Pesnicak L, Straus SE.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192147
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Nectin2[alpha] (PRR2[alpha] or HveB) and Nectin2[delta] Are Low-Efficiency Mediators for Entry of Herpes Simplex Virus Mutants Carrying the Leu25Pro Substitution in Glycoprotein D. by Lopez M, Cocchi F, Menotti L, Avitabile E, Dubreuil P, Campadelli-Fiume G.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111461
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Neither LAT nor Open Reading Frame P Mutations Increase Expression of Spliced or Intron-Containing ICP0 Transcripts in Mouse Ganglia Latently Infected with Herpes Simplex Virus. by Chen SH, Lee LY, Garber DA, Schaffer PA, Knipe DM, Coen DM.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136172
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Neurons Differentially Activate the Herpes Simplex Virus Type 1 Immediate-Early Gene ICP0 and ICP27 Promoters in Transgenic Mice. by Loiacono CM, Myers R, Mitchell WJ.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153807
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Neutralizing Antibodies Inhibit Axonal Spread of Herpes Simplex Virus Type 1 to Epidermal Cells In Vitro. by Mikloska Z, Sanna PP, Cunningham AL.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112655
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Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea. by Tumpey TM, Chen SH, Oakes JE, Lausch RN.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189893
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Neutrophils Aid in Protection of the Vaginal Mucosae of Immune Mice against Challenge with Herpes Simplex Virus Type 2. by Milligan GN.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112717
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Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice. by Luker GD, Bardill JP, Prior JL, Pica CM, PiwnicaWorms D, Leib DA.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136903
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Novel Approach for Specific Detection of Herpes Simplex Virus Type 1 and 2 Antibodies and Immunoglobulin G and M Antibodies. by Ohana B, Lipson M, Vered N, Srugo I, Ahdut M, Morag A.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95983
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Novel Class of Thiourea Compounds That Inhibit Herpes Simplex Virus Type 1 DNA Cleavage and Encapsidation: Resistance Maps to the UL6 Gene. by van Zeijl M, Fairhurst J, Jones TR, Vernon SK, Morin J, LaRocque J, Feld B, O'Hara B, Bloom JD, Johann SV.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102102
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Novel, Soluble Isoform of the Herpes Simplex Virus (HSV) Receptor Nectin1 (or PRR1-HIgR-HveC) Modulates Positively and Negatively Susceptibility to HSV Infection. by Lopez M, Cocchi F, Avitabile E, Leclerc A, Adelaide J, Campadelli-Fiume G, Dubreuil P.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114282
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NP-1, a Rabbit [alpha]-Defensin, Prevents the Entry and Intercellular Spread of Herpes Simplex Virus Type 2. by Sinha S, Cheshenko N, Lehrer RI, Herold BC.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151743
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Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14. by Donnelly M, Elliott G.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115879
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Nuclear sites of herpes simplex virus type 1 DNA replication and transcription colocalize at early times postinfection and are largely distinct from RNA processing factors. by Phelan A, Dunlop J, Patel AH, Stow ND, Clements JB.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191164
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Optimized Viral Dose and Transient Immunosuppression Enable Herpes Simplex Virus ICP0-Null Mutants To Establish Wild-Type Levels of Latency In Vivo. by Halford WP, Schaffer PA.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112092
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Oral Bioavailability and In Vivo Efficacy of the Helicase-Primase Inhibitor BILS 45 BS against Acyclovir-Resistant Herpes Simplex Virus Type 1. by Duan J, Liuzzi M,
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Paris W, Liard F, Browne A, Dansereau N, Simoneau B, Faucher AM, Cordingley MG.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155846 •
Oral inoculation with herpes simplex virus type 1 infects enteric neuron and mucosal nerve fibers within the gastrointestinal tract in mice. by Gesser RM, Koo SC.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190294
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Origin Binding Protein-Containing Protein-DNA Complex Formation at Herpes Simplex Virus Type 1 oriS: Role in oriS-Dependent DNA Replication. by Isler JA, Schaffer PA.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114407
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Overexpression of Interleukin-2 by a Recombinant Herpes Simplex Virus Type 1 Attenuates Pathogenicity and Enhances Antiviral Immunity. by Ghiasi H, Osorio Y, Perng GC, Nesburn AB, Wechsler SL.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136420
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Overexpression of the herpes simplex virus type 1 immediate-early regulatory protein, ICP27, is responsible for the aberrant localization of ICP0 and mutant forms of ICP4 in ICP4 mutant virus-infected cells. by Zhu Z, DeLuca NA, Schaffer PA.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190492
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Packaging of Genomic and Amplicon DNA by the Herpes Simplex Virus Type 1 UL25-Null Mutant KUL25NS. by Stow ND.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114657
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Packaging-Competent Capsids of a Herpes Simplex Virus Temperature-Sensitive Mutant Have Properties Similar to Those of In Vitro-Assembled Procapsids. by Rixon FJ, McNab D.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112631
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Pathogenesis of Herpes Simplex Virus Type 1-Induced Corneal Inflammation in Perforin-Deficient Mice. by Chang E, Galle L, Maggs D, Estes DM, Mitchell WJ.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112466
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Pathogenesis of Herpes Simplex Virus Type 2 Virion Host Shutoff (vhs) Mutants. by Smith TJ, Morrison LA, Leib DA.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153813
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Pathogenesis of Herpes Simplex Virus-Induced Ocular Immunoinflammatory Lesions in B-Cell-Deficient Mice. by Deshpande SP, Zheng M, Daheshia M, Rouse BT.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111859
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Penciclovir Susceptibilities of Herpes Simplex Virus Isolates from Patients Using Penciclovir Cream for Treatment of Recurrent Herpes Labialis. by Sarisky RT, Bacon T, Boon R, Locke L, Nguyen TT, Leary J, Esser K, Saltzman R.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127441
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Performance of Two Commercial Glycoprotein G-Based Enzyme Immunoassays for Detecting Antibodies to Herpes Simplex Viruses 1 and 2 in Children and Young Adolescents. by Leach CT, Ashley RL, Baillargeon J, Jenson HB.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120053
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Persistence and Expression of the Herpes Simplex Virus Genome in the Absence of Immediate-Early Proteins. by Samaniego LA, Neiderhiser L, DeLuca NA.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109808
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Persistence of Herpes Simplex Virus Type 1 DNA in Chronic Conjunctival and Eyelid Lesions of Mice. by Maggs DJ, Chang E, Nasisse MP, Mitchell WJ.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110335
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Persistence of Infectious Herpes Simplex Virus Type 2 in the Nervous System in Mice after Antiviral Chemotherapy. by Thackray AM, Field HJ.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89634
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Perturbation of Cell Cycle Progression and Cellular Gene Expression as a Function of Herpes Simplex Virus ICP0. by Hobbs WE II, DeLuca NA.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112842
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Phosphorylation of Structural Components Promotes Dissociation of the Herpes Simplex Virus Type 1 Tegument. by Morrison EE, Wang YF, Meredith DM.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109932
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Phosphorylation of the Herpes Simplex Virus Type 1 Origin Binding Protein. by Isler JA, Schaffer PA.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113959
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Phosphorylation of Transcription Factor Sp1 during Herpes Simplex Virus Type 1 Infection. by Kim DB, DeLuca NA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136260
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Picornavirus Internal Ribosome Entry Site Elements Target RNA Cleavage Events Induced by the Herpes Simplex Virus Virion Host Shutoff Protein. by Elgadi MM, Smiley JR.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112956
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Plasma versus Serum for Detection of Herpes Simplex Virus Type 2-Specific Immunoglobulin G Antibodies with a Glycoprotein G2-Based Enzyme Immunoassay. by Cherpes TL, Meyn LA, Hillier SL.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156559
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Pocket Protein p130/Rb2 Is Required for Efficient Herpes Simplex Virus Type 1 Gene Expression and Viral Replication. by Ehmann GL, Burnett HA, Bachenheimer SL.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114444
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Posttranslational Processing of Infected Cell Proteins 0 and 4 of Herpes Simplex Virus 1 Is Sequential and Reflects the Subcellular Compartment in Which the Proteins Localize. by Advani SJ, Hagglund R, Weichselbaum RR, Roizman B.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115034
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Potent In Vivo Antiviral Activity of the Herpes Simplex Virus Primase-Helicase Inhibitor BAY 57-1293. by Betz UA, Fischer R, Kleymann G, Hendrix M, RubsamenWaigmann H.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127257
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Potential Role for Luman, the Cellular Homologue of Herpes Simplex Virus VP16 ([alpha] Gene trans-Inducing Factor), in Herpesvirus Latency. by Lu R, Misra V.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111614
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Processing of [alpha]-Globin and ICP0 mRNA in Cells Infected with Herpes Simplex Virus Type 1 ICP27 Mutants. by Ellison KS, Rice SA, Verity R, Smiley JR.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112251
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Progesterone Increases Susceptibility and Decreases Immune Responses to Genital Herpes Infection. by Kaushic C, Ashkar AA, Reid LA, Rosenthal KL.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152159
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Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection. by Su YH, Yan XT, Oakes JE, Lausch RN.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189943
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Protective Mucosal Immunity to Ocular Herpes Simplex Virus Type 1 Infection in Mice by Using Escherichia coli Heat-Labile Enterotoxin B Subunit as an Adjuvant. by Richards CM, Aman AT, Hirst TR, Hill TJ, Williams NA.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114075
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Protective T-Cell-Based Immunity Induced in Neonatal Mice by a Single Replicative Cycle of Herpes Simplex Virus. by Franchini M, Abril C, Schwerdel C, Ruedl C, Ackermann M, Suter M.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113900
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Proteolytic Cleavage of the Amino Terminus of the UL15 Gene Product of Herpes Simplex Virus Type 1 Is Coupled with Maturation of Viral DNA into Unit-Length Genomes. by Salmon B, Nalwanga D, Fan Y, Baines JD.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112851
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PrPc Expression Influences the Establishment of Herpes Simplex Virus Type 1 Latency. by Thackray AM, Bujdoso R.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153799
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Pseudotyping of Glycoprotein D-Deficient Herpes Simplex Virus Type 1 with Vesicular Stomatitis Virus Glycoprotein G Enables Mutant Virus Attachment and Entry. by Anderson DB, Laquerre S, Goins WF, Cohen JB, Glorioso JC.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111736
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Quantitation of herpes simplex virus type 1 DNA and latency-associated transcripts in rabbit trigeminal ganglia demonstrates a stable reservoir of viral nucleic acids during latency. by Hill JM, Gebhardt BM, Wen R, Bouterie AM, Thompson HW, O'Callaghan RJ, Halford WP, Kaufman HE.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190176
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Quantitation of Latent Varicella-Zoster Virus and Herpes Simplex Virus Genomes in Human Trigeminal Ganglia. by Pevenstein SR, Williams RK, McChesney D, Mont EK, Smialek JE, Straus SE.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113107
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Quantitative Analysis of Herpes Simplex Virus Reactivation In Vivo Demonstrates that Reactivation in the Nervous System Is Not Inhibited at Early Times Postinoculation. by Sawtell NM.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150616
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Rapid Detection and Typing of Herpes Simplex Virus DNA in Clinical Specimens by the Hybrid Capture II Signal Amplification Probe Test. by Michalski FJ.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104646
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Rapid detection and typing of herpes simplex virus DNA in clinical specimens by the hybrid capture II signal amplification probe test. by Cullen AP, Long CD, Lorincz AT.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229953
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Rapid Detection of Herpes Simplex Virus and Varicella-Zoster Virus Infections by Real-Time PCR. by Weidmann M, Meyer-Konig U, Hufert FT.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153887
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Rapid Phenotypic Characterization Method for Herpes Simplex Virus and VaricellaZoster Virus Thymidine Kinases To Screen for Acyclovir-Resistant Viral Infection. by Suzutani T, Saijo M, Nagamine M, Ogasawara M, Azuma M.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86603
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Rapid Screening Tests for Determining In Vitro Susceptibility of Herpes Simplex Virus Clinical Isolates. by de la Iglesia P, Melon S, Lopez B, Rodriguez M, Blanco MI, Mellado P, de Ona M.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105060
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Ras-GAP Binding and Phosphorylation by Herpes Simplex Virus Type 2 RR1 PK (ICP10) and Activation of the Ras/MEK/MAPK Mitogenic Pathway Are Required for Timely Onset of Virus Growth. by Smith CC, Nelson J, Aurelian L, Gober M, Goswami BB.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110916
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Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by nucleoside. by Tenser RB, Gaydos A, Hay KA.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189942
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Recognition of Herpes Simplex Virus Type 2 Tegument Proteins by CD4 T Cells Infiltrating Human Genital Herpes Lesions. by Koelle DM, Frank JM, Johnson ML, Kwok WW.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109983
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Recombinant Herpes Simplex Virus Type 1 Engineered for Targeted Binding to Erythropoietin Receptor-Bearing Cells. by Laquerre S, Anderson DB, Stolz DB, Glorioso JC.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110478
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Recombinant Herpes Simplex Virus Type 1 Expressing Murine Interleukin-4 Is Less Virulent than Wild-Type Virus in Mice. by Ghiasi H, Osorio Y, Perng GC, Nesburn AB, Wechsler SL.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114471
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Recovery of an Unusual Fusogenic Herpes Simplex Virus Type 2 Strain from a Clinical Specimen. by Johnson FB.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130920
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Region of Herpes Simplex Virus Type 1 Latency-Associated Transcript Sufficient for Wild-Type Spontaneous Reactivation Promotes Cell Survival in Tissue Culture. by Inman M, Perng GC, Henderson G, Ghiasi H, Nesburn AB, Wechsler SL, Jones C.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114855
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Herpes Simplex
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Regional Distribution of Antibodies to Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 in Men and Women in Ontario, Canada. by Howard M, Sellors JW, Jang D, Robinson NJ, Fearon M, Kaczorowski J, Chernesky M.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149555
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Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo. by Ahmed M, Lock M, Miller CG, Fraser NW.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136840
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Regulation of herpes simplex virus [gamma]134.5 expression and oncolysis of diffuse liver metastases by Myb34.5. by Nakamura H, Kasuya H, Mullen JT, Yoon SS, Pawlik TM, Chandrasekhar S, Donahue JM, Chiocca EA, Chung RY, Tanabe KK.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150923
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Replication Fidelity of the supF Gene Integrated in the Thymidine Kinase Locus of Herpes Simplex Virus Type 1. by Hwang YT, Liu BY, Hwang CB.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136086
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Replication of Herpes Simplex Virus Type 1 within Trigeminal Ganglia Is Required for High Frequency but Not High Viral Genome Copy Number Latency. by Thompson RL, Sawtell NM.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111617
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Requirement for Cellular Cyclin-Dependent Kinases in Herpes Simplex Virus Replication and Transcription. by Schang LM, Phillips J, Schaffer PA.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110224
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Requirement of Interaction of Nectin-1[alpha]/HveC with Afadin for Efficient CellCell Spread of Herpes Simplex Virus Type 1. by Sakisaka T, Taniguchi T, Nakanishi H, Takahashi K, Miyahara M, Ikeda W, Yokoyama S, Peng YF, Yamanishi K, Takai Y.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114228
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Requirements for the Induction of Interleukin-6 by Herpes Simplex Virus-Infected Leukocytes. by Paludan SR.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115044
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Requirements for the Nuclear-Cytoplasmic Translocation of Infected-Cell Protein 0 of Herpes Simplex Virus 1. by Lopez P, Van Sant C, Roizman B.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114874
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RNA Polymerase II Holoenzyme Modifications Accompany Transcription Reprogramming in Herpes Simplex Virus Type 1-Infected Cells. by Jenkins HL, Spencer CA.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114559
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Role for Gamma Interferon in Control of Herpes Simplex Virus Type 1 Reactivation. by Cantin E, Tanamachi B, Openshaw H.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104106
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Role of CD28/CD80-86 and CD40/CD154 Costimulatory Interactions in Host Defense to Primary Herpes Simplex Virus Infection. by Edelmann KH, Wilson CB.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113957
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Role of Cyclin D3 in the Biology of Herpes Simplex Virus 1 ICP0. by Van Sant C, Lopez P, Advani SJ, Roizman B.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115135
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Role of histamine in natural killer cell-dependent protection against herpes simplex virus type 2 infection in mice. by Hellstrand K, Asea A, Hermodsson S.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170145
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Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus. by Lee S, Zheng M, Kim B, Rouse BT.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150797
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Role of the UL25 Gene Product in Packaging DNA into the Herpes Simplex Virus Capsid: Location of UL25 Product in the Capsid and Demonstration that It Binds DNA. by Ogasawara M, Suzutani T, Yoshida I, Azuma M.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114049
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Role of the virion host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. by Strelow LI, Leib DA.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189589
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Roles of different T-cell subsets in control of herpes simplex virus infection determined by using T-cell-deficient mouse-models. by Manickan E, Rouse BT.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189778
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Roscovitine, a Specific Inhibitor of Cellular Cyclin-Dependent Kinases, Inhibits Herpes Simplex Virus DNA Synthesis in the Presence of Viral Early Proteins. by Schang LM, Rosenberg A, Schaffer PA.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111691
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Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8 + cytotoxic T lymphocyte responses. by Posavad CM, Koelle DM, Shaughnessy MF, Corey L.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23355
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Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers. by Orle KA, Gates CA, Martin DH, Body BA, Weiss JB.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228728
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Site-Directed Mutagenesis of the Virion Host Shutoff Gene (UL41) of Herpes Simplex Virus (HSV): Analysis of Functional Differences between HSV Type 1 (HSV-1) and HSV-2 Alleles. by Everly DN Jr, Read GS.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112944
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Small Dense Nuclear Bodies Are the Site of Localization of Herpes Simplex Virus 1 UL3 and UL4 Proteins and of ICP22 Only When the Latter Protein Is Present. by Markovitz NS, Roizman B.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111565
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Social stress and the reactivation of latent herpes simplex virus type 1. by Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R.; 1998 Jun 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22787
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Sodium Lauryl Sulfate Increases the Efficacy of a Topical Formulation of Foscarnet against Herpes Simplex Virus Type 1 Cutaneous Lesions in Mice. by Piret J, Desormeaux A, Cormier H, Lamontagne J, Gourde P, Juhasz J, Bergeron MG.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90056
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Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. by Feldman LT, Ellison AR, Voytek CC, Yang L, Krause P, Margolis TP.; 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117416
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Structural and Antigenic Analysis of a Truncated Form of the Herpes Simplex Virus Glycoprotein gH-gL Complex. by Peng T, Ponce de Leon M, Novotny MJ, Jiang H, Lambris JD, Dubin G, Spear PG, Cohen GH, Eisenberg RJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110415
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Surveillance for Antiviral-Agent-Resistant Herpes Simplex Virus in the General Population with Recurrent Herpes Labialis. by Bacon TH, Boon RJ, Schultz M, HodgesSavola C.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127455
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Survey of Resistance of Herpes Simplex Virus to Acyclovir in Northwest England. by Christophers J, Clayton J, Craske J, Ward R, Collins P, Trowbridge M, Darby G.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105557
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Tegument-Specific, Virus-Reactive CD4 T Cells Localize to the Cornea in Herpes Simplex Virus Interstitial Keratitis in Humans. by Koelle DM, Reymond SN, Chen H, Kwok WW, McClurkan C, Gyaltsong T, Petersdorf EW, Rotkis W, Talley AR, Harrison DA.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113172
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Temporal Regulation of Herpes Simplex Virus Type 2 VP22 Expression and Phosphorylation. by Geiss BJ, Tavis JE, Metzger LM, Leib DA, Morrison LA.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114653
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The 2.2-Kilobase Latency-Associated Transcript of Herpes Simplex Virus Type 2 Does Not Modulate Viral Replication, Reactivation, or Establishment of Latency in Transgenic Mice. by Wang K, Pesnicak L, Guancial E, Krause PR, Straus SE.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115061
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The 60-Residue C-Terminal Region of the Single-Stranded DNA Binding Protein of Herpes Simplex Virus Type 1 Is Required for Cooperative DNA Binding. by Mapelli M, Muhleisen M, Persico G, van der Zandt H, Tucker PA.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102075
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The Ability of Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 To Bind to a Ubiquitin-Specific Protease Contributes to Its Roles in the Activation of Gene Expression and Stimulation of Virus Replication. by Everett RD, Meredith M, Orr A.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103848
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The abundant latency-associated transcripts of herpes simplex virus type 1 are bound to polyribosomes in cultured neuronal cells and during latent infection in mouse trigeminal ganglia. by Goldenberg D, Mador N, Ball MJ, Panet A, Steiner I.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191416
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The Antiviral Efficacy of the Murine Alpha-1 Interferon Transgene against Ocular Herpes Simplex Virus Type 1 Requires the Presence of CD4 +, [alpha]/[beta] T-Cell Receptor-Positive T Lymphocytes with the Capacity To Produce Gamma Interferon. by Carr DJ, Noisakran S.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136437
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The Conserved Carboxyl-Terminal Half of Herpes Simplex Virus Type 1 Regulatory Protein ICP27 Is Dispensable for Viral Growth in the Presence of Compensatory Mutations. by Bunnell SM, Rice SA.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112256
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The Cytotoxic T-Cell Response to Herpes Simplex Virus Type 1 Infection of C57BL/6 Mice Is Almost Entirely Directed against a Single Immunodominant Determinant. by Wallace ME, Keating R, Heath WR, Carbone FR.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104289
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The Disappearance of Cyclins A and B and the Increase in Activity of the G2/M-Phase Cellular Kinase cdc2 in Herpes Simplex Virus 1-Infected Cells Require Expression of the [alpha]22/US1.5 and UL13 Viral Genes. by Advani SJ, Brandimarti R, Weichselbaum RR, Roizman B.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111507
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The Domains of Glycoprotein D Required To Block Apoptosis Depend on Whether Glycoprotein D Is Present in the Virions Carrying Herpes Simplex Virus 1 Genome Lacking the Gene Encoding the Glycoprotein. by Zhou G, Roizman B.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114332
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The Early Expression of Glycoprotein B from Herpes Simplex Virus Can Be Detected by Antigen-Specific CD8 + T Cells. by Mueller SN, Jones CM, Chen W, Kawaoka Y, Castrucci MR, Heath WR, Carbone FR.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141123
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The Ectodomain of a Novel Member of the Immunoglobulin Subfamily Related to the Poliovirus Receptor Has the Attributes of a Bona Fide Receptor for Herpes Simplex Virus Types 1 and 2 in Human Cells. by Cocchi F, Menotti L, Mirandola P, Lopez M, Campadelli-Fiume G.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110516
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The essential protein encoded by the UL31 gene of herpes simplex virus 1 depends for its stability on the presence of UL34 protein. by Ye GJ, Roizman B.; 2000 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27138
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The estimated economic burden of genital herpes in the United States. An analysis using two costing approaches. by Szucs TD, Berger K, Fisman DN, Harbarth S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35281
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The First Immunoglobulin-Like Domain of HveC Is Sufficient To Bind Herpes Simplex Virus gD with Full Affinity, While the Third Domain Is Involved in Oligomerization of HveC. by Krummenacher C, Rux AH, Whitbeck JC, Ponce-de-Leon M, Lou H, Baribaud I, Hou W, Zou C, Geraghty RJ, Spear PG, Eisenberg RJ, Cohen GH.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112829
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The Genome Sequence of Herpes Simplex Virus Type 2. by Dolan A, Jamieson FE, Cunningham C, Barnett BC, McGeoch DJ.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109494
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The gH-gL Complex of Herpes Simplex Virus (HSV) Stimulates Neutralizing Antibody and Protects Mice against HSV Type 1 Challenge. by Peng T, Ponce-de-Leon M, Jiang H, Dubin G, Lubinski JM, Eisenberg RJ, Cohen GH.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109350
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The Herpes Simplex Virus gE-gI Complex Facilitates Cell-to-Cell Spread and Binds to Components of Cell Junctions. by Dingwell KS, Johnson DC.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110310
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The Herpes Simplex Virus Type 1 Cleavage/Packaging Protein, UL32, Is Involved in Efficient Localization of Capsids to Replication Compartments. by Lamberti C, Weller SK.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109547
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The Herpes Simplex Virus Type 1 Regulatory Protein ICP27 Is Required for the Prevention of Apoptosis in Infected Human Cells. by Aubert M, Blaho JA.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104038
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The Herpes Simplex Virus Type 1 UL17 Gene Encodes Virion Tegument Proteins That Are Required for Cleavage and Packaging of Viral DNA. by Salmon B, Cunningham C, Davison AJ, Harris WJ, Baines JD.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109600
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The Herpes Simplex Virus Type 1 US11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain. by Cassady KA, Gross M.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135940
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The Herpes Simplex Virus US11 Protein Effectively Compensates for the [gamma]134.5 Gene if Present before Activation of Protein Kinase R by Precluding Its Phosphorylation and That of the [alpha] Subunit of Eukaryotic Translation Initiation Factor 2. by Cassady KA, Gross M, Roizman B.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110273
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The Herpes Simplex Virus vhs Protein Induces Endoribonucleolytic Cleavage of Target RNAs in Cell Extracts. by Elgadi MM, Hayes CE, Smiley JR.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104239
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The High Mobility Group Protein 1 Is a Coactivator of Herpes Simplex Virus ICP4 In Vitro. by Carrozza MJ, DeLuca N.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109883
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The Latency-Associated Transcript Gene Enhances Establishment of Herpes Simplex Virus Type 1 Latency in Rabbits. by Perng GC, Slanina SM, Yukht A, Ghiasi H, Nesburn AB, Wechsler SL.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111666
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The Latent Herpes Simplex Virus Type 1 Genome Copy Number in Individual Neurons Is Virus Strain Specific and Correlates with Reactivation. by Sawtell NM, Poon DK, Tansky CS, Thompson RL.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110155
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The Major Neutralizing Antigenic Site on Herpes Simplex Virus Glycoprotein D Overlaps a Receptor-Binding Domain. by Whitbeck JC, Muggeridge MI, Rux AH, Hou W, Krummenacher C, Lou H, van Geelen A, Eisenberg RJ, Cohen GH.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113037
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The NH2 Terminus of the Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Contains a Promoter-Specific Transcription Activation Domain. by Lium EK, Panagiotidis CA, Wen X, Silverstein SJ.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110090
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The PK Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Is Required for Immediate-Early Gene Expression and Virus Growth. by Smith CC, Peng T, Kulka M, Aurelian L.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110331
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The Polyserine Tract of Herpes Simplex Virus ICP4 Is Required for Normal Viral Gene Expression and Growth in Murine Trigeminal Ganglia. by Bates PA, DeLuca NA.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109933
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The Probability of In Vivo Reactivation of Herpes Simplex Virus Type 1 Increases with the Number of Latently Infected Neurons in the Ganglia. by Sawtell NM.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109900
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The Product of the Herpes Simplex Virus Type 1 UL25 Gene Is Required for Encapsidation but Not for Cleavage of Replicated Viral DNA. by McNab AR, Desai P, Person S, Roof LL, Thomsen DR, Newcomb WW, Brown JC, Homa FL.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124578
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The Quantity of Latent Viral DNA Correlates with the Relative Rates at Which Herpes Simplex Virus Types 1 and 2 Cause Recurrent Genital Herpes Outbreaks. by Lekstrom-Himes JA, Pesnicak L, Straus SE.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109720
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The range and distribution of murine central nervous system cells infected with the gamma(1)34.5- mutant of herpes simplex virus 1. by Markovitz NS, Baunoch D, Roizman B.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191798
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The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation. by Perng GC, Chokephaibulkit K, Thompson RL, Sawtell NM, Slanina SM, Ghiasi H, Nesburn AB, Wechsler SL.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189815
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The role of cdc2 in the expression of herpes simplex virus genes. by Advani SJ, Weichselbaum RR, Roizman B.; 2000 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27137
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The Role of Herpes Simplex Virus ICP27 in the Regulation of UL24 Gene Expression by Differential Polyadenylation. by Hann LE, Cook WJ, Uprichard SL, Knipe DM, Coen DM.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110073
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The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1.5 kilobases of the 8.3-kilobase primary transcript. by Perng GC, Ghiasi H, Slanina SM, Nesburn AB, Wechsler SL.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189902
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The Spread of Herpes Simplex Virus Type 1 from Trigeminal Neurons to the Murine Cornea: an Immunoelectron Microscopy Study. by Ohara PT, Chin MS, LaVail JH.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112000
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The T-cell-independent role of gamma interferon and tumor necrosis factor alpha in macrophage activation during murine cytomegalovirus and herpes simplex virus infections. by Heise MT, Virgin HW 4th.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188658
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The Transgenic ICP4 Promoter Is Activated in Schwann Cells in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus Type 1. by Taus NS, Mitchell WJ.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114614
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The transneuronal spread phenotype of herpes simplex virus type 1 infection of the mouse hind footpad. by Engel JP, Madigan TC, Peterson GM.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191353
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The UL3 Protein of Herpes Simplex Virus 1 Is Translated Predominantly from the Second In-Frame Methionine Codon and Is Subject to at Least Two Posttranslational Modifications. by Markovitz NS, Filatov F, Roizman B.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112816
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The UL6 Gene Product Forms the Portal for Entry of DNA into the Herpes Simplex Virus Capsid. by Newcomb WW, Juhas RM, Thomsen DR, Homa FL, Burch AD, Weller SK, Brown JC.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114672
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The US3 Protein Kinase Blocks Apoptosis Induced by the d120 Mutant of Herpes Simplex Virus 1 at a Premitochondrial Stage. by Munger J, Chee AV, Roizman B.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114261
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The vhs1 Mutant Form of Herpes Simplex Virus Virion Host Shutoff Protein Retains Significant Internal Ribosome Entry Site-Directed RNA Cleavage Activity. by Lu P, Saffran HA, Smiley JR.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114006
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Therapeutic Immunization with a Virion Host Shutoff-Defective, ReplicationIncompetent Herpes Simplex Virus Type 1 Strain Limits Recurrent Herpetic Ocular Infection. by Keadle TL, Morrison LA, Morris JL, Pepose JS, Stuart PM.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136075
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Three Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutants with Distinct and Asymmetric Effects on Virulence in Mice Compared with Rabbits. by Perng GC, Esmaili D, Slanina SM, Yukht A, Ghiasi H, Osorio N, Mott KR, Maguen B, Jin L, Nesburn AB, Wechsler SL.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114470
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Time-Resolved Fluorometry PCR Assay for Rapid Detection of Herpes Simplex Virus in Cerebrospinal Fluid. by Hukkanen V, Rehn T, Kajander R, Sjoroos M, Waris M.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87359
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Tracking the Spread of a lacZ-Tagged Herpes Simplex Virus Type 1 between the Eye and the Nervous System of the Mouse: Comparison of Primary and Recurrent Infection. by Shimeld C, Efstathiou S, Hill T.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114931
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Transcription of Herpes Simplex Virus Immediate-Early and Early Genes Is Inhibited by Roscovitine, an Inhibitor Specific for Cellular Cyclin-Dependent Kinases. by Schang LM, Rosenberg A, Schaffer PA.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104461
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Translational Compensation of a Frameshift Mutation Affecting Herpes Simplex Virus Thymidine Kinase Is Sufficient To Permit Reactivation from Latency. by Griffiths A, Chen SH, Horsburgh BC, Coen DM.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152167
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Truncation of the C-Terminal Acidic Transcriptional Activation Domain of Herpes Simplex Virus VP16 Renders Expression of the Immediate-Early Genes Almost Entirely Dependent on ICP0. by Mossman KL, Smiley JR.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113019
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Typing of Clinical Herpes Simplex Virus Type 1 and Type 2 Isolates with Monoclonal Antibodies. by Liljeqvist JA, Svennerholm B, Bergstrom T.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85325
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UL27.5 Is a Novel [gamma]2 Gene Antisense to the Herpes Simplex Virus 1 Gene Encoding Glycoprotein B. by Chang YE, Menotti L, Filatov F, Campadelli-Fiume G, Roizman B.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110411
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UL31 and UL34 Proteins of Herpes Simplex Virus Type 1 Form a Complex That Accumulates at the Nuclear Rim and Is Required for Envelopment of Nucleocapsids. by Reynolds AE, Ryckman BJ, Baines JD, Zhou Y, Liang L, Roller RJ.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115125
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Use of Differential Display Reverse Transcription-PCR To Reveal Cellular Changes during Stimuli That Result in Herpes Simplex Virus Type 1 Reactivation from Latency: Upregulation of Immediate-Early Cellular Response Genes TIS7, Interferon, and Interferon Regulatory Factor-1. by Tal-Singer R, Podrzucki W, Lasner TM, Skokotas A, Leary JJ, Fraser NW, Berger SL.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124603
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Use of Immunostimulatory Sequence-Containing Oligonucleotides as Topical Therapy for Genital Herpes Simplex Virus Type 2 Infection. by Pyles RB, Higgins D, Chalk C, Zalar A, Eiden J, Brown C, Van Nest G, Stanberry LR.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136753
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Vaccine-Induced Serum Immunoglobin Contributes to Protection from Herpes Simplex Virus Type 2 Genital Infection in the Presence of Immune T Cells. by Morrison LA, Zhu L, Thebeau LG.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114025
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Vaginal formulations of carrageenan protect mice from herpes simplex virus infection. by Zacharopoulos VR, Phillips DM.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170551
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Variability of the Glycoprotein G Gene in Clinical Isolates of Herpes Simplex Virus Type 1. by Rekabdar E, Tunback P, Liljeqvist JA, Bergstrom T.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95783
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Viral replication is required for induction of ocular immunopathology by herpes simplex virus. by Babu JS, Thomas J, Kanangat S, Morrison LA, Knipe DM, Rouse BT.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189793
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Virus-Cell Interactions Regulating Induction of Tumor Necrosis Factor Alpha Production in Macrophages Infected with Herpes Simplex Virus. by Paludan SR, Mogensen SC.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114591
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Visualization of Tegument-Capsid Interactions and DNA in Intact Herpes Simplex Virus Type 1 Virions. by Zhou ZH, Chen DH, Jakana J, Rixon FJ, Chiu W.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104084
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Zinc Salts Inactivate Clinical Isolates of Herpes Simplex Virus In Vitro. by Arens M, Travis S.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86580
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with herpes simplex, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “herpes simplex” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for herpes simplex (hyperlinks lead to article summaries): •
A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery. Author(s): Watts DH, Brown ZA, Money D, Selke S, Huang ML, Sacks SL, Corey L. Source: American Journal of Obstetrics and Gynecology. 2003 March; 188(3): 836-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634667&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A modification of the epidermal scarification model of herpes simplex virus infection to achieve a reproducible and uniform progression of disease. Author(s): Goel N, Docherty JJ, Fu MM, Zimmerman DH, Rosenthal KS. Source: Journal of Virological Methods. 2002 December; 106(2): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393145&dopt=Abstract
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A prospective study of genital herpes simplex virus type 2 infection in human immunodeficiency virus type 1 (HIV-1)-seropositive women: correlations with CD4 cell count and plasma HIV-1 RNA level. Author(s): Wright PW, Hoesley CJ, Squires KE, Croom-Rivers A, Weiss HL, Gnann JW Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 15; 36(2): 207-11. Epub 2003 Jan 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522754&dopt=Abstract
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A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus. Author(s): Fu X, Meng F, Tao L, Jin A, Zhang X. Source: Gene Therapy. 2003 August; 10(17): 1458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900760&dopt=Abstract
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Activation of latent Lyme borreliosis concurrent with a herpes simplex virus type 1 infection. Author(s): Gylfe A, Wahlgren M, Fahlen L, Bergstrom S. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(12): 922-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587627&dopt=Abstract
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Activation of the human endogenous retrovirus W long terminal repeat by herpes simplex virus type 1 immediate early protein 1. Author(s): Lee WJ, Kwun HJ, Kim HS, Jang KL. Source: Molecules and Cells. 2003 February 28; 15(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661764&dopt=Abstract
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Acute cerebellitis caused by herpes simplex virus type 1. Author(s): Ciardi M, Giacchetti G, Fedele CG, Tenorio A, Brandi A, Libertone R, Ajassa C, Borgese L, Delia S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 1; 36(3): E50-4. Epub 2003 January 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539091&dopt=Abstract
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Adrenal insufficiency combined with gastric cardia ulcer due to herpes simplex virus type 1 infection. Author(s): Su CC, Lu JJ, Perng CL, Chen CS, Lee CC. Source: J Formos Med Assoc. 2002 October; 101(10): 719-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517048&dopt=Abstract
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Adults with atopic dermatitis and herpes simplex and topical therapy with tacrolimus: what kind of prevention? Author(s): Lubbe J, Sanchez-Politta S, Tschanz C, Saurat JH. Source: Archives of Dermatology. 2003 May; 139(5): 670-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756112&dopt=Abstract
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Amino acid changes within conserved region III of the herpes simplex virus and human cytomegalovirus DNA polymerases confer resistance to 4-oxodihydroquinolines, a novel class of herpesvirus antiviral agents. Author(s): Thomsen DR, Oien NL, Hopkins TA, Knechtel ML, Brideau RJ, Wathen MW, Homa FL. Source: Journal of Virology. 2003 February; 77(3): 1868-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525621&dopt=Abstract
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Amino acid substitutions in the effector domain of the gamma(1)34.5 protein of herpes simplex virus 1 have differential effects on viral response to interferon-alpha. Author(s): Cerveny M, Hessefort S, Yang K, Cheng G, Gross M, He B. Source: Virology. 2003 March 15; 307(2): 290-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667799&dopt=Abstract
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An uncommon case of disseminated neonatal herpes simplex infection presenting with pneumonia and pleural effusions. Author(s): Langlet C, Gaugler C, Castaing M, Astruc D, Falkenrodt A, Neuville A, Messer J. Source: European Journal of Pediatrics. 2003 July; 162(7-8): 532-3. Epub 2003 May 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733067&dopt=Abstract
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Analysis of the herpes simplex virus type 1 UL6 gene in patients with stromal keratitis. Author(s): Ellison AR, Yang L, Cevallos AV, Margolis TP. Source: Virology. 2003 May 25; 310(1): 24-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788627&dopt=Abstract
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Analysis of the role of the membrane-spanning and cytoplasmic tail domains of herpes simplex virus type 1 glycoprotein D in membrane fusion. Author(s): Browne H, Bruun B, Whiteley A, Minson T. Source: The Journal of General Virology. 2003 May; 84(Pt 5): 1085-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692272&dopt=Abstract
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Antiviral activity of Spirulina maxima against herpes simplex virus type 2. Author(s): Hernandez-Corona A, Nieves I, Meckes M, Chamorro G, Barron BL. Source: Antiviral Research. 2002 December; 56(3): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406511&dopt=Abstract
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Antiviral therapy in children with varicella zoster virus and herpes simplex virus infections. Author(s): Enright AM, Prober C. Source: Herpes : the Journal of the Ihmf. 2003 August; 10(2): 32-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14577952&dopt=Abstract
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Are latent, immediate-early genes of herpes simplex virus-1 essential in causing trigeminal neuralgia? Author(s): Ecker AD, Smith JE. Source: Medical Hypotheses. 2002 November; 59(5): 603-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376087&dopt=Abstract
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Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Author(s): Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 319-25. Epub 2003 July 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884154&dopt=Abstract
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Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. Author(s): Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Ruslanova I, Yolken RH. Source: Archives of General Psychiatry. 2003 May; 60(5): 466-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742867&dopt=Abstract
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Association of the herpes simplex virus type 1 Us11 gene product with the cellular kinesin light-chain-related protein PAT1 results in the redistribution of both polypeptides. Author(s): Benboudjema L, Mulvey M, Gao Y, Pimplikar SW, Mohr I. Source: Journal of Virology. 2003 September; 77(17): 9192-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915535&dopt=Abstract
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B7 costimulation plays an important role in protection from herpes simplex virus type 2-mediated pathology. Author(s): Thebeau LG, Morrison LA. Source: Journal of Virology. 2002 March; 76(5): 2563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836436&dopt=Abstract
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Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women. Author(s): Ridker PM, Hennekens CH, Buring JE, Kundsin R, Shih J. Source: Annals of Internal Medicine. 1999 October 19; 131(8): 573-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523217&dopt=Abstract
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Bcl-2 blocks a caspase-dependent pathway of apoptosis activated by herpes simplex virus 1 infection in HEp-2 cells. Author(s): Galvan V, Brandimarti R, Munger J, Roizman B. Source: Journal of Virology. 2000 February; 74(4): 1931-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10644366&dopt=Abstract
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BCL-2 transduction, using a herpes simplex virus amplicon, protects hippocampal neurons from transient global ischemia. Author(s): Antonawich FJ, Federoff HJ, Davis JN. Source: Experimental Neurology. 1999 March; 156(1): 130-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192784&dopt=Abstract
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Bilateral acute retinal necrosis and herpes simplex type 2 encephalitis in a neonate. Author(s): Kychenthal A, Coombes A, Greenwood J, Pavesio C, Aylward GW. Source: The British Journal of Ophthalmology. 2001 May; 85(5): 629-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351976&dopt=Abstract
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Bilateral necrotizing herpetic retinopathy three years after herpes simplex encephalitis following pulse corticosteroid treatment. Author(s): Verma L, Venkatesh P, Satpal G, Rathore K, Tewari HK. Source: Retina (Philadelphia, Pa.). 1999; 19(5): 464-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10546950&dopt=Abstract
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Binding partners for the UL11 tegument protein of herpes simplex virus type 1. Author(s): Loomis JS, Courtney RJ, Wills JW. Source: Journal of Virology. 2003 November; 77(21): 11417-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557627&dopt=Abstract
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Biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation. Author(s): Wu A, Mazumder A, Martuza RL, Liu X, Thein M, Meehan KR, Rabkin SD. Source: Cancer Research. 2001 April 1; 61(7): 3009-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306480&dopt=Abstract
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Biosynthetic ganciclovir triphosphate: its isolation and characterization from ganciclovir-treated herpes simplex thymidine kinase-transduced murine cells. Author(s): Agbaria R, Candotti F, Kelley JA, Hao Z, Johns DG, Cooney DA, Blaese RM, Ford H Jr. Source: Biochemical and Biophysical Research Communications. 2001 November 30; 289(2): 525-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716505&dopt=Abstract
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B-myb promoter retargeting of herpes simplex virus gamma34.5 gene-mediated virulence toward tumor and cycling cells. Author(s): Chung RY, Saeki Y, Chiocca EA. Source: Journal of Virology. 1999 September; 73(9): 7556-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438845&dopt=Abstract
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Bone marrow transplantation in a child with Wiskott-Aldrich syndrome latently infected with acyclovir-resistant (ACV(r)) herpes simplex virus type 1: emergence of foscarnet-resistant virus originating from the ACV(r) virus. Author(s): Saijo M, Yasuda Y, Yabe H, Kato S, Suzutani T, De Clercq E, Niikura M, Maeda A, Kurane I, Morikawa S. Source: Journal of Medical Virology. 2002 September; 68(1): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210436&dopt=Abstract
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Brain stem encephalitis caused by primary herpes simplex 2 infection in a young woman. Author(s): Tang JW, Coward LJ, Davies NW, Geretti AM, Howard RS, Hirsch NP, Ward KN. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933947&dopt=Abstract
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Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication. Author(s): Mesnil M, Yamasaki H. Source: Cancer Research. 2000 August 1; 60(15): 3989-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945596&dopt=Abstract
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Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes. Author(s): Walling HW, Swarthout JT, Culver KW. Source: Cancer Gene Therapy. 2000 February; 7(2): 187-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770626&dopt=Abstract
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Cell culture replication of herpes simplex virus and, or human cytomegalovirus is inhibited by 3,7-dialkoxylated, 1-hydroxyacridone derivatives. Author(s): Lowden CT, Bastow KF. Source: Antiviral Research. 2003 August; 59(3): 143-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927304&dopt=Abstract
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Cell response to herpes simplex virus type 1 infection mediated by biphasic calciumphosphate ceramics: in vitro approach. Author(s): Varadinova TL, Zlateva KT, Dyulgerova EI. Source: Journal of Biomedical Materials Research. 2001 November; 57(2): 232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484186&dopt=Abstract
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Cellular expression of gH confers resistance to herpes simplex virus type-1 entry. Author(s): Scanlan PM, Tiwari V, Bommireddy S, Shukla D. Source: Virology. 2003 July 20; 312(1): 14-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890617&dopt=Abstract
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Cesarean delivery and risk of herpes simplex virus infection. Author(s): Cohan D. Source: Jama : the Journal of the American Medical Association. 2003 May 7; 289(17): 2208; Author Reply 2208-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734124&dopt=Abstract
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Cesarean delivery and risk of herpes simplex virus infection. Author(s): Rouse DJ, Stringer JS. Source: Jama : the Journal of the American Medical Association. 2003 May 7; 289(17): 2208; Author Reply 2208-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734123&dopt=Abstract
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Characterization of a neurovirulent aciclovir-resistant variant of herpes simplex virus. Author(s): Grey F, Sowa M, Collins P, Fenton RJ, Harris W, Snowden W, Efstathiou S, Darby G. Source: The Journal of General Virology. 2003 June; 84(Pt 6): 1403-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771407&dopt=Abstract
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Chimeric Dr fimbriae with a herpes simplex virus type 1 epitope as a model for a recombinant vaccine. Author(s): Zalewska B, Piatek R, Konopa G, Nowicki B, Nowicki S, Kur J. Source: Infection and Immunity. 2003 October; 71(10): 5505-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500468&dopt=Abstract
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Chimeric nectin1-poliovirus receptor molecules identify a nectin1 region functional in herpes simplex virus entry. Author(s): Cocchi F, Lopez M, Dubreuil P, Campadelli Fiume G, Menotti L. Source: Journal of Virology. 2001 September; 75(17): 7987-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483743&dopt=Abstract
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Chlamydia trachomatis, herpes simplex virus 2, and human T-cell lymphotrophic virus type 1 are not associated with grade of cervical neoplasia in Jamaican colposcopy patients. Author(s): Castle PE, Escoffery C, Schachter J, Rattray C, Schiffman M, Moncada J, Sugai K, Brown C, Cranston B, Hanchard B, Palefsky JM, Burk RD, Hutchinson ML, Strickler HD. Source: Sexually Transmitted Diseases. 2003 July; 30(7): 575-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838087&dopt=Abstract
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Clinical aspects of recurrent oral herpes simplex virus infection. Author(s): Glick M. Source: Compend Contin Educ Dent. 2002 July; 23(7 Suppl 2): 4-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789980&dopt=Abstract
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Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial. Author(s): Sacks SL, Thisted RA, Jones TM, Barbarash RA, Mikolich DJ, Ruoff GE, Jorizzo JL, Gunnill LB, Katz DH, Khalil MH, Morrow PR, Yakatan GJ, Pope LE, Berg JE; Docosanol 10% Cream Study Group. Source: Journal of the American Academy of Dermatology. 2001 August; 45(2): 222-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464183&dopt=Abstract
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Clinical spectrum and laboratory characteristics associated with detection of herpes simplex virus DNA in cerebrospinal fluid. Author(s): O'Sullivan CE, Aksamit AJ, Harrington JR, Harmsen WS, Mitchell PS, Patel R. Source: Mayo Clinic Proceedings. 2003 November; 78(11): 1347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14601693&dopt=Abstract
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Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy. Author(s): Eisen D, Essell J, Broun ER, Sigmund D, DeVoe M. Source: Bone Marrow Transplantation. 2003 January; 31(1): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621507&dopt=Abstract
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Close association of predominant genotype of herpes simplex virus type 1 with eczema herpeticum analyzed using restriction fragment length polymorphism of polymerase chain reaction. Author(s): Yoshida M, Umene K. Source: Journal of Virological Methods. 2003 April; 109(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668262&dopt=Abstract
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Comparison of a monoclonal antibody-blocking enzyme-linked immunoassay and a strip immunoblot assay for identifying type-specific herpes simplex virus type 2 serological responses. Author(s): Van Doornum GJ, Slomka MJ, Buimer M, Groen J, Van den Hoek JA, Cairo I, Vyse A, Brown DW. Source: Clinical and Diagnostic Laboratory Immunology. 2000 July; 7(4): 641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882665&dopt=Abstract
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Comparison of polymorphism of thymidine kinase gene and restriction fragment length polymorphism of genomic DNA in herpes simplex virus type 1. Author(s): Nagamine M, Suzutani T, Saijo M, Hayashi K, Azuma M. Source: Journal of Clinical Microbiology. 2000 July; 38(7): 2750-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878078&dopt=Abstract
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Comparison of washing and swabbing procedures for collecting genital fluids to assess cervicovaginal shedding of herpes simplex virus type 2 DNA. Author(s): Ndjoyi-Mbiguino A, Ozouaki F, Legoff J, Mbopi-Keou FX, Si-Mohamed A, Onas IN, Avoune E, Belec L. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791898&dopt=Abstract
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Construction of multiply disabled herpes simplex viral vectors for gene delivery to the nervous system. Author(s): Lilley CE, Coffin RS. Source: Methods in Molecular Medicine. 2003; 76: 33-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526157&dopt=Abstract
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C-terminal region of herpes simplex virus ICP8 protein needed for intranuclear localization. Author(s): Taylor TJ, Knipe DM. Source: Virology. 2003 May 10; 309(2): 219-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12758170&dopt=Abstract
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Cytologic, colposcopic, and virologic detection of cervical herpes simplex virus. Author(s): Elnashar AM, Aboelea A, Tantawy TA. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 April; 81(1): 69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676402&dopt=Abstract
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Deletion of the virion host shutoff protein (vhs) from herpes simplex virus (HSV) relieves the viral block to dendritic cell activation: potential of vhs- HSV vectors for dendritic cell-mediated immunotherapy. Author(s): Samady L, Costigliola E, MacCormac L, McGrath Y, Cleverley S, Lilley CE, Smith J, Latchman DS, Chain B, Coffin RS. Source: Journal of Virology. 2003 March; 77(6): 3768-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610151&dopt=Abstract
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Detection of cutaneous herpes simplex virus infections by immunofluorescence vs. PCR. Author(s): Bezold G, Lange M, Gethoffer K, Gall H, Peter RU. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 July; 17(4): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834453&dopt=Abstract
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Detection of Herpes simplex virus DNA by real-time PCR. Author(s): Kessler HH, Muhlbauer G, Rinner B, Stelzl E, Berger A, Dorr HW, Santner B, Marth E, Rabenau H. Source: Journal of Clinical Microbiology. 2000 July; 38(7): 2638-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878056&dopt=Abstract
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Detection of herpes simplex virus DNA in dried blood spots making a retrospective diagnosis possible. Author(s): Ilona LF, Pia O, Marianne F, Gunilla M. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 January; 26(1): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589833&dopt=Abstract
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Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the semen of men attending an infertility clinic. Author(s): Kapranos N, Petrakou E, Anastasiadou C, Kotronias D. Source: Fertility and Sterility. 2003 June; 79 Suppl 3: 1566-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801561&dopt=Abstract
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Determination of minimum herpes simplex virus type 1 components necessary to localize transcriptionally active DNA to ND10. Author(s): Tang Q, Li L, Ishov AM, Revol V, Epstein AL, Maul GG. Source: Journal of Virology. 2003 May; 77(10): 5821-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719575&dopt=Abstract
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Diagnosis and management of recurrent herpes simplex induced by fixed prosthodontic tissue management: a clinical report. Author(s): Williamson RT. Source: The Journal of Prosthetic Dentistry. 1999 July; 82(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10384159&dopt=Abstract
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Diagnosis and management of recurrent herpes simplex infections. Author(s): Siegel MA. Source: The Journal of the American Dental Association. 2002 September; 133(9): 1245-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356256&dopt=Abstract
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Differences in the N termini of herpes simplex virus type 1 and 2 gDs that influence functional interactions with the human entry receptor Nectin-2 and an entry receptor expressed in Chinese hamster ovary cells. Author(s): Zago A, Spear PG. Source: Journal of Virology. 2003 September; 77(17): 9695-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915581&dopt=Abstract
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Differential mutation patterns in thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 clones passaged in the presence of acyclovir or penciclovir. Author(s): Suzutani T, Ishioka K, De Clercq E, Ishibashi K, Kaneko H, Kira T, Hashimoto K, Ogasawara M, Ohtani K, Wakamiya N, Saijo M. Source: Antimicrobial Agents and Chemotherapy. 2003 May; 47(5): 1707-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709344&dopt=Abstract
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Diffuse white matter lesions in a case of herpes simplex encephalitis. Author(s): Ueda N, Miyasaki H, Kuroiwa Y. Source: Journal of Neurology. 2003 July; 250(7): 867-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883931&dopt=Abstract
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Diffusion-weighted MR imaging findings in a patient with herpes simplex encephalitis. Author(s): Heiner L, Demaerel P. Source: European Journal of Radiology. 2003 March; 45(3): 195-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595103&dopt=Abstract
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Disabled infectious single cycle herpes simplex virus (DISC-HSV) is a candidate vector system for gene delivery/expression of GM-CSF in human prostate cancer therapy. Author(s): Parkinson RJ, Mian S, Bishop MC, Gray T, Li G, McArdle SE, Ali S, Rees RC. Source: The Prostate. 2003 June 15; 56(1): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746848&dopt=Abstract
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Disseminated cutaneous herpes simplex virus type-1 with interstitial pneumonia as a first presentation of AIDS. Author(s): Umar SH, Kanth A. Source: Journal of the National Medical Association. 1999 August; 91(8): 471-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656437&dopt=Abstract
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Disseminated herpes simplex after total skin electron beam radiotherapy for mycosis fungoides. Author(s): Smith BD, Son CB, Wilson LD. Source: Journal of the Royal Society of Medicine. 2003 October; 96(10): 500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519729&dopt=Abstract
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Divergence of reiterated sequences in a series of genital isolates of herpes simplex virus type 1 from individual patients. Author(s): Umene K, Kawana T. Source: The Journal of General Virology. 2003 April; 84(Pt 4): 917-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655092&dopt=Abstract
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Do we need antivirals for genital herpes simplex virus and human papillomavirus infection? Author(s): Gross G. Source: International Journal of Antimicrobial Agents. 1999 June; 12(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389641&dopt=Abstract
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Drug resistance patterns of recombinant herpes simplex virus DNA polymerase mutants generated with a set of overlapping cosmids and plasmids. Author(s): Bestman-Smith J, Boivin G. Source: Journal of Virology. 2003 July; 77(14): 7820-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829822&dopt=Abstract
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Dynamics of transgene expression in human glioblastoma cells mediated by herpes simplex virus/adeno-associated virus amplicon vectors. Author(s): Lam P, Hui KM, Wang Y, Allen PD, Louis DN, Yuan CJ, Breakefield XO. Source: Human Gene Therapy. 2002 December 10; 13(18): 2147-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542846&dopt=Abstract
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Dysregulated expression of IFN-gamma and IL-10 and impaired IFN-gammamediated responses at different disease stages in patients with genital herpes simplex virus-2 infection. Author(s): Singh R, Kumar A, Creery WD, Ruben M, Giulivi A, Diaz-Mitoma F. Source: Clinical and Experimental Immunology. 2003 July; 133(1): 97-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823283&dopt=Abstract
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Ectopic expression of herpes simplex virus-thymidine kinase gene in human nonsmall cell lung cancer cells conferred caspase-activated apoptosis sensitized by ganciclovir. Author(s): Chiu CC, Kang YL, Yang TH, Huang CH, Fang K. Source: International Journal of Cancer. Journal International Du Cancer. 2002 December 1; 102(4): 328-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402300&dopt=Abstract
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Effect of Ca2+-dependent cell death on the release of herpes simplex virus. Author(s): Yura Y, Matsumoto R, Sumi T, Kusaka J. Source: Archives of Virology. 2003 February; 148(2): 221-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556989&dopt=Abstract
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Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. Author(s): Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Source: Jama : the Journal of the American Medical Association. 2003 January 8; 289(2): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517231&dopt=Abstract
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Effective treatment of herpes simplex labialis with penciclovir cream: combined results of two trials. Author(s): Raborn GW, Martel AY, Lassonde M, Lewis MA, Boon R, Spruance SL; Worldwide Topical Penciclovir Collaborative Study Group. Source: The Journal of the American Dental Association. 2002 March; 133(3): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934185&dopt=Abstract
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Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells. Author(s): Wakimoto H, Johnson PR, Knipe DM, Chiocca EA. Source: Gene Therapy. 2003 June; 10(11): 983-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756419&dopt=Abstract
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Efficiency of reconstitution of immunoglobulin g from blood specimens dried on filter paper and utility in herpes simplex virus type-specific serology screening. Author(s): Hogrefe WR, Ernst C, Su X. Source: Clinical and Diagnostic Laboratory Immunology. 2002 November; 9(6): 1338-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414771&dopt=Abstract
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Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene. Author(s): Chalmers D, Ferrand C, Apperley JF, Melo JV, Ebeling S, Newton I, Duperrier A, Hagenbeek A, Garrett E, Tiberghien P, Garin M. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 August; 4(2): 146-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11482986&dopt=Abstract
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Emergence of herpes simplex type 1 as the main cause of recurrent genital ulcerative disease in women in Northern Ireland. Author(s): Coyle PV, O'Neill HJ, Wyatt DE, McCaughey C, Quah S, McBride MO. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 May; 27(1): 22-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727525&dopt=Abstract
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Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Author(s): Zhou G, Ye GJ, Debinski W, Roizman B. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 15124-9. Epub 2002 Nov 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417744&dopt=Abstract
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Entry of herpes simplex virus type 1 into primary sensory neurons in vitro is mediated by Nectin-1/HveC. Author(s): Richart SM, Simpson SA, Krummenacher C, Whitbeck JC, Pizer LI, Cohen GH, Eisenberg RJ, Wilcox CL. Source: Journal of Virology. 2003 March; 77(5): 3307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584355&dopt=Abstract
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Epidemiology of herpes simplex virus types 1 and 2 in Germany: what has changed? Author(s): Buxbaum S, Geers M, Gross G, Schofer H, Rabenau HF, Doerr HW. Source: Medical Microbiology and Immunology. 2003 August; 192(3): 177-81. Epub 2003 May 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761673&dopt=Abstract
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Erythema multiforme secondary to herpes simplex infection: a case report. Author(s): Ayangco L, Sheridan PJ, Rogers RS. Source: J Periodontol. 2001 July; 72(7): 953-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495145&dopt=Abstract
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Estimating the costs and benefits of screening monogamous, heterosexual couples for unrecognised infection with herpes simplex virus type 2. Author(s): Fisman DN, Hook EW 3rd, Goldie SJ. Source: Sexually Transmitted Infections. 2003 February; 79(1): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576614&dopt=Abstract
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Evidence against a simple tethering model for enhancement of herpes simplex virus DNA polymerase processivity by accessory protein UL42. Author(s): Chaudhuri M, Parris DS. Source: Journal of Virology. 2002 October; 76(20): 10270-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239303&dopt=Abstract
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Excretion of herpes simplex virus type 2 glycoprotein D into the culture medium. Author(s): Murata T, Goshima F, Takakuwa H, Nishiyama Y. Source: The Journal of General Virology. 2002 November; 83(Pt 11): 2791-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388815&dopt=Abstract
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Experimental use of natural interferon alpha by peroral administration in patients affected by recidivant herpes simplex. Author(s): Pisani M, Bozzi M. Source: Clin Ter. 2000; 151(1 Suppl 1): 19-22. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10876962&dopt=Abstract
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Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role. Author(s): Morris SJ, Smith H, Sweet C. Source: Archives of Virology. 2002 May; 147(5): 961-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021867&dopt=Abstract
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Exploiting virus stealth technology for xenotransplantation: reduced human T cell responses to porcine cells expressing herpes simplex virus ICP47. Author(s): Crew MD, Phanavanh B. Source: Xenotransplantation. 2003 January; 10(1): 50-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535225&dopt=Abstract
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Expression of human immunodeficiency virus type 1 gp120 from herpes simplex virus type 1-derived amplicons results in potent, specific, and durable cellular and humoral immune responses. Author(s): Hocknell PK, Wiley RD, Wang X, Evans TG, Bowers WJ, Hanke T, Federoff HJ, Dewhurst S. Source: Journal of Virology. 2002 June; 76(11): 5565-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991985&dopt=Abstract
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Extramammary Paget's disease with superimposed herpes simplex virus infection: immunohistochemical comparison with cases of the two respective diseases. Author(s): Yamamoto O, Yasuda H. Source: The British Journal of Dermatology. 2003 June; 148(6): 1258-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828759&dopt=Abstract
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Facial herpes simplex: autoinoculation by an intubation mask. Author(s): Martineau MR, Chapman MS. Source: The Journal of Trauma. 2002 August; 53(2): 389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169957&dopt=Abstract
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Failure to genotype herpes simplex virus by real-time PCR assay and melting curve analysis due to sequence variation within probe binding sites. Author(s): Anderson TP, Werno AM, Beynon KA, Murdoch DR. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734260&dopt=Abstract
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Famiciclovir therapy (famvir) for herpes simplex and herpes zoster infections. Author(s): Tyring S. Source: Skin Therapy Letter. 2001 November; 6(12): 1-2, 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753535&dopt=Abstract
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Familial herpes simplex encephalitis. Author(s): Jackson AC, Melanson M, Rossiter JP. Source: Annals of Neurology. 2002 March; 51(3): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891839&dopt=Abstract
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Fatal disseminated herpes simplex virus infection in a previously healthy pregnant woman. A case report. Author(s): Frederick DM, Bland D, Gollin Y. Source: J Reprod Med. 2002 July; 47(7): 591-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170540&dopt=Abstract
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Fatal herpes simplex virus hepatitis complicating chemotherapy with weekly docetaxel. Author(s): Hofer S, Hunziker S, Tornillo L, Ludwig CU. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562665&dopt=Abstract
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Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection. Author(s): Scott ES, O'Hare P. Source: Journal of Virology. 2001 September; 75(18): 8818-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507226&dopt=Abstract
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Fetal demise due to herpes simplex virus: an illustrated case report. Author(s): Barefoot KH, Little GA, Ornvold KT. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 January; 22(1): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840250&dopt=Abstract
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Findings in a patient with herpes simplex viral meningitis associated with acute retinal necrosis syndrome. Author(s): Tada Y, Negoro K, Morimatsu M, Makino H, Nishida T. Source: Ajnr. American Journal of Neuroradiology. 2001 August; 22(7): 1300-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498417&dopt=Abstract
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Five cases of fulminant hepatitis due to herpes simplex virus in adults. Author(s): Pinna AD, Rakela J, Demetris AJ, Fung JJ. Source: Digestive Diseases and Sciences. 2002 April; 47(4): 750-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991604&dopt=Abstract
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Florid CD4+, CD56+ T-cell infiltrate associated with Herpes simplex infection simulating nasal NK-/T-cell lymphoma. Author(s): Taddesse-Heath L, Feldman JI, Fahle GA, Fischer SH, Sorbara L, Raffeld M, Jaffe ES. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2003 February; 16(2): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591970&dopt=Abstract
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Frequency of herpes simplex virus in Syria based on type-specific serological assay. Author(s): Ibrahim AI, Kouwatli KM, Obeid MT. Source: Saudi Med J. 2000 April; 21(4): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533818&dopt=Abstract
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Frequency of herpes simplex virus, cytomegalovirus and human papillomavirus DNA in semen. Author(s): Aynaud O, Poveda JD, Huynh B, Guillemotonia A, Barrasso R. Source: International Journal of Std & Aids. 2002 August; 13(8): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194737&dopt=Abstract
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Friendly fire: redirecting herpes simplex virus-1 for therapeutic applications. Author(s): Advani SJ, Weichselbaum RR, Whitley RJ, Roizman B. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 September; 8(9): 551-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427216&dopt=Abstract
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Frontal impairment and confabulation after herpes simplex encephalitis: A case report. Author(s): Del Grosso Destreri N, Farina E, Calabrese E, Pinardi G, Imbornone E, Mariani C. Source: Archives of Physical Medicine and Rehabilitation. 2002 March; 83(3): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887126&dopt=Abstract
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Fulminant course of herpes simplex virus reactivation in an apparently immunocompetent woman. Author(s): Tischendorf JJ, Grosse V, Flik J, Verhagen W, Manns MP, Trautwein C. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 June; 7(2): 160-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839720&dopt=Abstract
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Fulminant hepatic failure due to herpes simplex after hysteroscopy. Author(s): Price TM, Harris JB. Source: Obstetrics and Gynecology. 2001 November; 98(5 Pt 2): 954-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704219&dopt=Abstract
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Fulminant hepatic failure from herpes simplex in pregnancy. Author(s): Nagappan R, Parkin G, Simpson I, Sievert W. Source: The Medical Journal of Australia. 2002 June 17; 176(12): 595-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064959&dopt=Abstract
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Function of dynein and dynactin in herpes simplex virus capsid transport. Author(s): Dohner K, Wolfstein A, Prank U, Echeverri C, Dujardin D, Vallee R, Sodeik B. Source: Molecular Biology of the Cell. 2002 August; 13(8): 2795-809. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181347&dopt=Abstract
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Functional characterization of the HveA homolog specified by African green monkey kidney cells with a herpes simplex virus expressing the green fluorescence protein. Author(s): Foster TP, Chouljenko VN, Kousoulas KG. Source: Virology. 1999 June 5; 258(2): 365-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10366573&dopt=Abstract
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Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells. Author(s): Shaw MM, Gurr WK, Watts PA, Littler E, Field HJ. Source: Antivir Chem Chemother. 2001 May; 12(3): 175-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959326&dopt=Abstract
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Gene delivery using herpes simplex virus vectors. Author(s): Burton EA, Fink DJ, Glorioso JC. Source: Dna and Cell Biology. 2002 December; 21(12): 915-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573050&dopt=Abstract
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Gene therapy for treatment of cerebral ischemia using defective herpes simplex viral vectors. Author(s): Yenari MA, Dumas TC, Sapolsky RM, Steinberg GK. Source: Neurological Research. 2001 July; 23(5): 543-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474812&dopt=Abstract
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Gene therapy for treatment of cerebral ischemia using defective herpes simplex viral vectors. Author(s): Yenari MA, Dumas TC, Sapolsky RM, Steinberg GK. Source: Annals of the New York Academy of Sciences. 2001 June; 939: 340-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11462790&dopt=Abstract
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Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. Author(s): Barzon L, Bonaguro R, Castagliuolo I, Chilosi M, Franchin E, Del Vecchio C, Giaretta I, Boscaro M, Palu G. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 January; 148(1): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534360&dopt=Abstract
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Gene therapy with herpes simplex virus vectors: progress and prospects for clinical neuroscience. Author(s): Latchman DS. Source: The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 2001 December; 7(6): 528-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765130&dopt=Abstract
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General and specific alterations in programming of global viral gene expression during infection by VP16 activation-deficient mutants of herpes simplex virus type 1. Author(s): Yang WC, Devi-Rao GV, Ghazal P, Wagner EK, Triezenberg SJ. Source: Journal of Virology. 2002 December; 76(24): 12758-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438601&dopt=Abstract
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Generation of fusion genes carrying drug resistance, green fluorescent protein, and herpes simplex virus thymidine kinase genes in a single cistron. Author(s): Oh SC, Nam SY, Kwon HC, Kim CM, Seo JS, Seong RH, Jang YJ, Chung YH, Chung HY. Source: Molecules and Cells. 2001 April 30; 11(2): 192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355700&dopt=Abstract
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Genetic characterization of thymidine kinase from acyclovir-resistant and susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients. Author(s): Morfin F, Souillet G, Bilger K, Ooka T, Aymard M, Thouvenot D. Source: The Journal of Infectious Diseases. 2000 July; 182(1): 290-3. Epub 2000 June 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882609&dopt=Abstract
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Genetically engineered herpes simplex viral vectors in the treatment of brain tumors: a review. Author(s): Aghi M, Chiocca EA. Source: Cancer Investigation. 2003 April; 21(2): 278-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743992&dopt=Abstract
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Genetically engineered human herpes simplex virus in the treatment of brain tumours. Author(s): Markert JM, Parker JN, Gillespie GY, Whitley RJ. Source: Herpes : the Journal of the Ihmf. 2001 March; 8(1): 17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867012&dopt=Abstract
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Genital herpes simplex infections: some therapeutic dilemmas. Author(s): Mills J, Mindel A. Source: Sexually Transmitted Diseases. 2003 March; 30(3): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616142&dopt=Abstract
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Genital herpes simplex virus infection in the adolescent: special considerations for management. Author(s): Stanberry LR, Rosenthal SL. Source: Paediatric Drugs. 2002; 4(5): 291-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994034&dopt=Abstract
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Genital herpes simplex virus type 1 infection: new fields for an old acquaintance? Author(s): Lippelt L, Braun RW, Kuhn JE. Source: Intervirology. 2002; 45(1): 2-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937764&dopt=Abstract
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Genital shedding of herpes simplex virus among men. Author(s): Wald A, Zeh J, Selke S, Warren T, Ashley R, Corey L. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353185&dopt=Abstract
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Genital shedding of herpes simplex virus-2 DNA and HIV-1 RNA and proviral DNA in HIV-1- and herpes simplex virus-2-coinfected African women. Author(s): Mbopi-Keou FX, Legoff J, Gresenguet G, Si-Mohamed A, Matta M, Mayaud P, Andreoletti L, Malkin JE, Weiss H, Brown D, Belec L. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 June 1; 33(2): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794542&dopt=Abstract
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Genotyping of herpes simplex virus type 1 strains isolated from ocular materials of patients with herpetic keratitis. Author(s): Umene K, Inoue T, Inoue Y, Shimomura Y. Source: Journal of Medical Virology. 2003 September; 71(1): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858412&dopt=Abstract
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Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules. Author(s): Sievers E, Neumann J, Raftery M, SchOnrich G, Eis-Hubinger AM, Koch N. Source: Immunology. 2002 September; 107(1): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225371&dopt=Abstract
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Glycosaminoglycan-binding ability is a feature of wild-type strains of herpes simplex virus type 1. Author(s): Trybala E, Roth A, Johansson M, Liljeqvist JA, Rekabdar E, Larm O, Bergstrom T. Source: Virology. 2002 October 25; 302(2): 413-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441085&dopt=Abstract
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Graft failure in human donor corneas due to transmission of herpes simplex virus. Author(s): Biswas S, Suresh P, Bonshek RE, Corbitt G, Tullo AB, Ridgway AE. Source: The British Journal of Ophthalmology. 2000 July; 84(7): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873977&dopt=Abstract
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Herpes simplex encephalitis and radiotherapy. Author(s): Riel-Romero RM, Baumann RJ. Source: Pediatric Neurology. 2003 July; 29(1): 69-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679127&dopt=Abstract
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Herpes simplex encephalitis. Author(s): Hu Z, Yang Q, Bo X, Li J. Source: Lancet. 2003 July 26; 362(9380): 280. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892957&dopt=Abstract
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Herpes simplex encephalitis. A study of seven patients and their immunological response prior to routine acyclovir treatment. Author(s): Bell JB, Davies RA, Thompson EJ. Source: The Journal of Infection. 2003 August; 47(2): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860151&dopt=Abstract
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Herpes simplex thymidine kinase gene-transduced donor lymphocyte infusions. Author(s): Burt RK, Drobyski WR, Seregina T, Traynor A, Oyama Y, Keever-Taylor C, Stefka J, Kuzel TM, Brush M, Rodriquez J, Burns W, Tennant L, Link C. Source: Experimental Hematology. 2003 October; 31(10): 903-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14550806&dopt=Abstract
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Herpes simplex type-1 virus infection. Author(s): Huber MA. Source: Quintessence Int. 2003 June; 34(6): 453-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859090&dopt=Abstract
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Herpes simplex virus and Meniere's disease. Author(s): Vrabec JT. Source: The Laryngoscope. 2003 September; 113(9): 1431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972911&dopt=Abstract
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Herpes simplex virus causing superficial wound infection in total hip arthroplasty. Author(s): Alexander P, Wismer D. Source: The Journal of Arthroplasty. 2003 June; 18(4): 516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820099&dopt=Abstract
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Herpes simplex virus DNA in corneal transplants: prospective study of 38 recipients. Author(s): Robert PY, Adenis JP, Denis F, Alain S, Ranger-Rogez S. Source: Journal of Medical Virology. 2003 September; 71(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858411&dopt=Abstract
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Herpes simplex virus glycoproteins gD and gE/gI serve essential but redundant functions during acquisition of the virion envelope in the cytoplasm. Author(s): Farnsworth A, Goldsmith K, Johnson DC. Source: Journal of Virology. 2003 August; 77(15): 8481-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857917&dopt=Abstract
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Herpes simplex virus infections of the central nervous system. Author(s): Kimberlin DW. Source: Seminars in Pediatric Infectious Diseases. 2003 April; 14(2): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881795&dopt=Abstract
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Herpes simplex virus triggers activation of calcium-signaling pathways. Author(s): Cheshenko N, Del Rosario B, Woda C, Marcellino D, Satlin LM, Herold BC. Source: The Journal of Cell Biology. 2003 October 27; 163(2): 283-93. Epub 2003 Oct 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568989&dopt=Abstract
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Herpes simplex virus type 1 exhibits a tropism for basal entry in polarized epithelial cells. Author(s): Schelhaas M, Jansen M, Haase I, Knebel-Morsdorf D. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2473-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917468&dopt=Abstract
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Herpes simplex virus type 1 glycoprotein B sorting in hippocampal neurons. Author(s): Potel C, Kaelin K, Danglot L, Triller A, Vannier C, Rozenberg F. Source: The Journal of General Virology. 2003 October; 84(Pt 10): 2613-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679595&dopt=Abstract
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Herpes simplex virus type 1 targets the MHC class II processing pathway for immune evasion. Author(s): Neumann J, Eis-Hubinger AM, Koch N. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 September 15; 171(6): 307583. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960333&dopt=Abstract
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Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT. Author(s): van Leeuwen H, Okuwaki M, Hong R, Chakravarti D, Nagata K, O'Hare P. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2501-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917472&dopt=Abstract
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Herpes simplex virus type 2 as a cause of severe meningitis in immunocompromised adults. Author(s): Mommeja-Marin H, Lafaurie M, Scieux C, Galicier L, Oksenhendler E, Molina JM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): 1527-33. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614676&dopt=Abstract
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Herpes simplex virus type 2 seropositivity in a sexually transmitted disease clinic in Israel. Author(s): Feldman PA, Steinberg J, Madeb R, Bar G, Nativ O, Tal J, Srugo I. Source: Isr Med Assoc J. 2003 September; 5(9): 626-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509150&dopt=Abstract
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Herpes simplex virus vectors for Parkinson's disease. Author(s): Latchman DS. Source: Int Rev Neurobiol. 2003; 55: 223-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968539&dopt=Abstract
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Herpes simplex virus-associated sepsis in a previously infected immunocompetent adult. Author(s): Zahariadis G, Jerome KR, Corey L. Source: Annals of Internal Medicine. 2003 July 15; 139(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859170&dopt=Abstract
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Hypertrophic herpes simplex virus in HIV patients. Author(s): Fangman WL, Rao CH, Myers SA. Source: J Drugs Dermatol. 2003 April; 2(2): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852374&dopt=Abstract
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Identification of a novel human sand family protein in human fibroblasts induced by herpes simplex virus 1 binding. Author(s): Dong S, Dong C, Liu L, Che Y, Sun M, Hu F, Li J, Li Q. Source: Acta Virol. 2003; 47(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828340&dopt=Abstract
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Identification of herpes simplex virus DNA and lack of human herpesvirus-8 DNA in mycosis fungoides. Author(s): Erkek E, Senturk N, Dincer I, Olut AI, Kocagoz T, Bukulmez G, Sahin S. Source: Acta Dermato-Venereologica. 2002; 82(3): 214-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353718&dopt=Abstract
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Identification of herpes simplex virus type 1 latency-associated transcript sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. Author(s): Jin L, Peng W, Perng GC, Brick DJ, Nesburn AB, Jones C, Wechsler SL. Source: Journal of Virology. 2003 June; 77(11): 6556-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743314&dopt=Abstract
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Identification, localization, and regulation of expression of the UL24 protein of herpes simplex virus type 1. Author(s): Pearson A, Coen DM. Source: Journal of Virology. 2002 November; 76(21): 10821-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368325&dopt=Abstract
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Imaging of the varicella zoster virion in the viral highways: comparison with herpes simplex viruses 1 and 2, cytomegalovirus, pseudorabies virus, and human herpes viruses 6 and 7. Author(s): Padilla JA, Nii S, Grose C. Source: Journal of Medical Virology. 2003; 70 Suppl 1: S103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627497&dopt=Abstract
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Impact of process conditions on the centrifugal recovery of a disabled herpes simplex virus. Author(s): Lotfian P, Levy MS, Coffin RS, Fearn T, Ayazi-Shamlou P. Source: Biotechnology Progress. 2003 January-February; 19(1): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573027&dopt=Abstract
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In vitro antiviral activity of Phyllanthus orbicularis extracts against herpes simplex virus type 1. Author(s): Fernandez Romero JA, Del Barrio Alonso G, Romeu Alvarez B, Gutierrez Y, Valdes VS, Parra F. Source: Phytotherapy Research : Ptr. 2003 September; 17(8): 980-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13680841&dopt=Abstract
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In vitro thymidine kinase/ganciclovir-based suicide gene therapy using replication defective herpes simplex virus-1 against leukemic B-cell malignancies (MCL, HCL, BCLL). Author(s): Misumi M, Suzuki T, Moriuchi S, Glorioso JC, Bessho M. Source: Leukemia Research. 2003 August; 27(8): 695-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801527&dopt=Abstract
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Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus. Author(s): Weber O, Siegling A, Friebe A, Limmer A, Schlapp T, Knolle P, Mercer A, Schaller H, Volk HD. Source: The Journal of General Virology. 2003 July; 84(Pt 7): 1843-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810878&dopt=Abstract
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Incidence and prevalence of herpes simplex virus type 2 infection in persons seeking repeat HIV counseling and testing. Author(s): Turner KR, McFarland W, Kellogg TA, Wong E, Page-Shafer K, Louie B, Dilley J, Kent CK, Klausner J. Source: Sexually Transmitted Diseases. 2003 April; 30(4): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671554&dopt=Abstract
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Inflammatory optic neuropathy as the presenting feature of herpes simplex acute retinal necrosis. Author(s): Francis PJ, Jackson H, Stanford MR, Graham EM. Source: The British Journal of Ophthalmology. 2003 April; 87(4): 512-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642331&dopt=Abstract
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Inhibition of herpes simplex virus 1 gene expression by designer zinc-finger transcription factors. Author(s): Papworth M, Moore M, Isalan M, Minczuk M, Choo Y, Klug A. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 18; 100(4): 1621-6. Epub 2003 Feb 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574501&dopt=Abstract
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Inhibition of PACT-mediated activation of PKR by the herpes simplex virus type 1 Us11 protein. Author(s): Peters GA, Khoo D, Mohr I, Sen GC. Source: Journal of Virology. 2002 November; 76(21): 11054-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368348&dopt=Abstract
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Interventions for herpes simplex virus epithelial keratitis. Author(s): Wilhelmus KR. Source: Cochrane Database Syst Rev. 2003; (3): Cd002898. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917935&dopt=Abstract
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Intracellular localization of Herpes simplex virus type 1 thymidine kinase fused to different fluorescent proteins depends on choice of fluorescent tag. Author(s): Soling A, Simm A, Rainov N. Source: Febs Letters. 2002 September 11; 527(1-3): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220652&dopt=Abstract
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Intracranial hemorrhage in herpes simplex encephalitis: an unusual presentation. Author(s): Erdem G, Vanderford PA, Bart RD. Source: Pediatric Neurology. 2002 September; 27(3): 221-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393133&dopt=Abstract
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Intrauterine herpes simplex infection. Author(s): Vasileiadis GT, Roukema HW, Romano W, Walton JC, Gagnon R. Source: American Journal of Perinatology. 2003 February; 20(2): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660908&dopt=Abstract
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Involvement of apolipoprotein E in the hematogenous route of herpes simplex virus type 1 to the central nervous system. Author(s): Burgos JS, Ramirez C, Sastre I, Bullido MJ, Valdivieso F. Source: Journal of Virology. 2002 December; 76(23): 12394-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414984&dopt=Abstract
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Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus. Author(s): Bradley JD, Kataoka Y, Advani S, Chung SM, Arani RB, Gillespie GY, Whitley RJ, Markert JM, Roizman B, Weichselbaum RR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 June; 5(6): 1517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389941&dopt=Abstract
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Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase. Author(s): Stanziale SF, Petrowsky H, Joe JK, Roberts GD, Zager JS, Gusani NJ, BenPorat L, Gonen M, Fong Y. Source: Surgery. 2002 August; 132(2): 353-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219034&dopt=Abstract
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Kinetic analysis of glycoprotein C of herpes simplex virus types 1 and 2 binding to heparin, heparan sulfate, and complement component C3b. Author(s): Rux AH, Lou H, Lambris JD, Friedman HM, Eisenberg RJ, Cohen GH. Source: Virology. 2002 March 15; 294(2): 324-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009874&dopt=Abstract
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Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)methanocarba-thymidine. Author(s): Prota A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G, Scapozza L. Source: Biochemistry. 2000 August 8; 39(31): 9597-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924157&dopt=Abstract
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La Crosse encephalitis presenting like herpes simplex encephalitis in an immunocompromised adult. Author(s): Wurtz R, Paleologos N. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 October; 31(4): 1113-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11049801&dopt=Abstract
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LaCrosse viral encephalitis mimics herpes simplex viral encephalitis. Author(s): Sokol DK, Kleiman MB, Garg BP. Source: Pediatric Neurology. 2001 November; 25(5): 413-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744319&dopt=Abstract
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Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Author(s): Andersen JH, Jenssen H, Gutteberg TJ. Source: Antiviral Research. 2003 May; 58(3): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767468&dopt=Abstract
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Large-scale comparison of experimental adjuvants with herpes simplex virus vaccine reveals a correlation of protection with IgG2a and IgG2b responses. Author(s): Simms JR, Jennings R, Richardson VJ, Heath AW. Source: Journal of Medical Virology. 2002 September; 68(1): 82-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210434&dopt=Abstract
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Late recurrence of herpes simplex virus meningoencephalitis in two infants. Author(s): Mandyla H, Anagnostakis D, Koutsovitis P, Siahanidou T, Youroukos S. Source: European Journal of Pediatrics. 2001 December; 160(12): 732-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795682&dopt=Abstract
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Latent herpes simplex virus infection of sensory neurons alters neuronal gene expression. Author(s): Kramer MF, Cook WJ, Roth FP, Zhu J, Holman H, Knipe DM, Coen DM. Source: Journal of Virology. 2003 September; 77(17): 9533-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915567&dopt=Abstract
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Latent herpes simplex virus-1 infection in SCID mice transferred with immune CD4+T cells: a new model for latency. Author(s): Minagawa H, Yanagi Y. Source: Archives of Virology. 2000; 145(11): 2259-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205116&dopt=Abstract
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Latent multiple infections by herpes simplex virus type 1. Author(s): Fujita H. Source: Kurume Med J. 2000; 47(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10948654&dopt=Abstract
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Limits of early diagnosis of herpes simplex encephalitis in children: a retrospective study of 38 cases. Author(s): De Tiege X, Heron B, Lebon P, Ponsot G, Rozenberg F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 15; 36(10): 1335-9. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746782&dopt=Abstract
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Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletion. Author(s): Herraiz M, Beraza N, Solano A, Sangro B, Montoya J, Qian C, Prieto J, Bustos M. Source: Human Gene Therapy. 2003 March 20; 14(5): 463-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691611&dopt=Abstract
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Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2. Author(s): Ashkar AA, Bauer S, Mitchell WJ, Vieira J, Rosenthal KL. Source: Journal of Virology. 2003 August; 77(16): 8948-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885911&dopt=Abstract
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Localization of a binding site for herpes simplex virus glycoprotein D on herpesvirus entry mediator C by using antireceptor monoclonal antibodies. Author(s): Krummenacher C, Baribaud I, Ponce de Leon M, Whitbeck JC, Lou H, Cohen GH, Eisenberg RJ. Source: Journal of Virology. 2000 December; 74(23): 10863-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069980&dopt=Abstract
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Localization of the gD-binding region of the human herpes simplex virus receptor, HveA. Author(s): Whitbeck JC, Connolly SA, Willis SH, Hou W, Krummenacher C, Ponce de Leon M, Lou H, Baribaud I, Eisenberg RJ, Cohen GH. Source: Journal of Virology. 2001 January; 75(1): 171-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119586&dopt=Abstract
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Localized herpes simplex lymphadenitis mimicking large-cell (Richter's) transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma. Author(s): Joseph L, Scott MA, Schichman SA, Zent CS. Source: American Journal of Hematology. 2001 December; 68(4): 287-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754420&dopt=Abstract
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Long term persistence of herpes simplex virus-specific CD8+ CTL in persons with frequently recurring genital herpes. Author(s): Posavad CM, Huang ML, Barcy S, Koelle DM, Corey L. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 July 15; 165(2): 1146-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878394&dopt=Abstract
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Longitudinal reliability of focus glycoprotein G-based type-specific enzyme immunoassays for detection of herpes simplex virus types 1 and 2 in women. Author(s): Cherpes TL, Ashley RL, Meyn LA, Hillier SL. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 671-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574265&dopt=Abstract
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Longitudinal study of genital infection by herpes simplex virus type 1 in Western Scotland over 15 years. Author(s): Scoular A, Norrie J, Gillespie G, Mir N, Carman WF. Source: Bmj (Clinical Research Ed.). 2002 June 8; 324(7350): 1366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052804&dopt=Abstract
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Long-term prophylactic antiviral therapy for recurrent herpes simplex: the controversy goes on. Author(s): Wolf R, Wolf D, Orion E, Matz H. Source: Clinics in Dermatology. 2003 March-April; 21(2): 164-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706334&dopt=Abstract
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Lower interleukin-2 and higher serum tumor necrosis factor-a levels are associated with perimenstrual, recurrent, facial Herpes simplex infection in young women. Author(s): Mysliwska J, Trzonkowski P, Bryl E, Lukaszuk K, Mysliwski A. Source: Eur Cytokine Netw. 2000 September; 11(3): 397-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022124&dopt=Abstract
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Luman, the cellular counterpart of herpes simplex virus VP16, is processed by regulated intramembrane proteolysis. Author(s): Raggo C, Rapin N, Stirling J, Gobeil P, Smith-Windsor E, O'Hare P, Misra V. Source: Molecular and Cellular Biology. 2002 August; 22(16): 5639-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138176&dopt=Abstract
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Management of acute ulcerative and necrotising herpes simplex and zoster keratitis with amniotic membrane transplantation. Author(s): Heiligenhaus A, Li H, Hernandez Galindo EE, Koch JM, Steuhl KP, Meller D. Source: The British Journal of Ophthalmology. 2003 October; 87(10): 1215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507749&dopt=Abstract
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Management of acyclovir-resistant herpes simplex virus. Author(s): Chilukuri S, Rosen T. Source: Dermatologic Clinics. 2003 April; 21(2): 311-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757254&dopt=Abstract
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Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry. Author(s): Herold BC, Scordi-Bello I, Cheshenko N, Marcellino D, Dzuzelewski M, Francois F, Morin R, Casullo VM, Anderson RA, Chany C 2nd, Waller DP, Zaneveld LJ, Klotman ME. Source: Journal of Virology. 2002 November; 76(22): 11236-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388683&dopt=Abstract
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Maternal Herpes simplex virus type 2 encephalitis following Cesarean section. Author(s): Godet C, Beby-Defaux A, Agius G, Pourrat O, Robert R. Source: The Journal of Infection. 2003 August; 47(2): 174-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860155&dopt=Abstract
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Membrane association of VP22, a herpes simplex virus type 1 tegument protein. Author(s): Brignati MJ, Loomis JS, Wills JW, Courtney RJ. Source: Journal of Virology. 2003 April; 77(8): 4888-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663795&dopt=Abstract
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Molecular approaches to detecting herpes simplex virus and enteroviruses in the central nervous system. Author(s): Smalling TW, Sefers SE, Li H, Tang YW. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2317-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089241&dopt=Abstract
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Molecular basis of the interactions between herpes simplex viruses and HIV-1. Author(s): Palu G, Benetti L, Calistri A. Source: Herpes : the Journal of the Ihmf. 2001 July; 8(2): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867019&dopt=Abstract
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Molecular diagnosis of herpes simplex virus infections in the central nervous system. Author(s): Tang YW, Mitchell PS, Espy MJ, Smith TF, Persing DH. Source: Journal of Clinical Microbiology. 1999 July; 37(7): 2127-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364574&dopt=Abstract
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Morphologic, immunohistochemical, immunologic, ultrastructural, and time-related study of herpes simplex virus type 1-infected cultured human fibroblasts. Author(s): Jensen HL, Norrild B. Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication of the Society for Applied Immunohistochemistry. 2002 March; 10(1): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893041&dopt=Abstract
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Multiplex polymerase chain reaction for detection of herpes simplex virus type 1, type 2, cytomegalovirus, and varicella-zoster virus in ocular viral infections. Author(s): Zhang Y, Kimura T, Fujiki K, Sakuma H, Murakami A, Kanai A. Source: Japanese Journal of Ophthalmology. 2003 May-June; 47(3): 260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782161&dopt=Abstract
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Mutant herpes simplex virus-mediated suppression of retinoblastoma. Author(s): Kogishi J, Miyatake S, Hangai M, Akimoto M, Okazaki K, Honda Y. Source: Current Eye Research. 1999 May; 18(5): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372992&dopt=Abstract
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Mutation of the protein tyrosine kinase consensus site in the herpes simplex virus 1 alpha22 gene alters ICP22 posttranslational modification. Author(s): O'Toole JM, Aubert M, Kotsakis A, Blaho JA. Source: Virology. 2003 January 5; 305(1): 153-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504549&dopt=Abstract
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Mutation spectra of herpes simplex virus type 1 thymidine kinase mutants. Author(s): Lu Q, Hwang YT, Hwang CB. Source: Journal of Virology. 2002 June; 76(11): 5822-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992012&dopt=Abstract
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Mutations in the N termini of herpes simplex virus type 1 and 2 gDs alter functional interactions with the entry/fusion receptors HVEM, nectin-2, and 3-O-sulfated heparan sulfate but not with nectin-1. Author(s): Yoon M, Zago A, Shukla D, Spear PG. Source: Journal of Virology. 2003 September; 77(17): 9221-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915538&dopt=Abstract
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Natural history of genital herpes simplex virus type 1 infection. Author(s): Engelberg R, Carrell D, Krantz E, Corey L, Wald A. Source: Sexually Transmitted Diseases. 2003 February; 30(2): 174-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567178&dopt=Abstract
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Natural history of neonatal herpes simplex virus infections in the acyclovir era. Author(s): Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Soong SJ, Kiell J, Lakeman FD, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Source: Pediatrics. 2001 August; 108(2): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483781&dopt=Abstract
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Need for diagnostic screening of Herpes simplex virus in patients with nongonococcal urethritis. Author(s): Madeb R, Nativ O, Benilevi D, Feldman PA, Halachmi S, Srugo I. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 June; 30(6): 982-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880323&dopt=Abstract
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Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum. Author(s): Malm G, Forsgren M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1999 July; 81(1): F24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375358&dopt=Abstract
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Neonatal herpes simplex: pulmonary and intracranial findings. Author(s): Carey BE. Source: Neonatal Netw. 2002 September-October; 21(6): 63-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240514&dopt=Abstract
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Neonatal liver transplantation for fulminant hepatitis caused by herpes simplex virus type 2. Author(s): Lee WS, Kelly DA, Tanner MS, Ramani P, de Ville de Goyet J, McKiernan PJ. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 August; 35(2): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187302&dopt=Abstract
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NF-kappaB is required for apoptosis prevention during herpes simplex virus type 1 infection. Author(s): Goodkin ML, Ting AT, Blaho JA. Source: Journal of Virology. 2003 July; 77(13): 7261-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805425&dopt=Abstract
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Nodular perianal herpes simplex with prominent plasma cell infiltration. Author(s): Gubinelli E, Cocuroccia B, Lazzarotto T, Girolomoni G. Source: Sexually Transmitted Diseases. 2003 February; 30(2): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567175&dopt=Abstract
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Novel agents and strategies to treat herpes simplex virus infections. Author(s): Kleymann G. Source: Expert Opinion on Investigational Drugs. 2003 February; 12(2): 165-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556212&dopt=Abstract
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Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient. Author(s): Chibo D, Mijch A, Doherty R, Birch C. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2002 August; 25(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367650&dopt=Abstract
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Oct-1 is posttranslationally modified and exhibits reduced capacity to bind cognate sites at late times after infection with herpes simplex virus 1. Author(s): Advani SJ, Durand LO, Weichselbaum RR, Roizman B. Source: Journal of Virology. 2003 November; 77(22): 11927-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581529&dopt=Abstract
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Oncolytic herpes simplex virus for tumor therapy. Author(s): Hu JC, Coffin RS. Source: Int Rev Neurobiol. 2003; 55: 165-84. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968536&dopt=Abstract
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Oncolytic herpes simplex virus vectors for cancer virotherapy. Author(s): Varghese S, Rabkin SD. Source: Cancer Gene Therapy. 2002 December; 9(12): 967-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522436&dopt=Abstract
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Oncolytic viral therapy for human ovarian cancer using a novel replication-competent herpes simplex virus type I mutant in a mouse model. Author(s): Nawa A, Nozawa N, Goshima F, Nagasaka T, Kikkawa F, Niwa Y, Nakanishi T, Kuzuya K, Nishiyama Y. Source: Gynecologic Oncology. 2003 October; 91(1): 81-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529666&dopt=Abstract
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Oncolytic virus therapy using genetically engineered herpes simplex viruses. Author(s): Todo T. Source: Hum Cell. 2002 September; 15(3): 151-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703545&dopt=Abstract
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One in the eye for herpes simplex virus. Author(s): Wood I. Source: Trends in Pharmacological Sciences. 2002 August; 23(8): 355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377572&dopt=Abstract
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Optimisation of herpes simplex virus-based vectors for delivery to human peripheral blood mononuclear cells. Author(s): Papageorgiou K, Isenberg DA, Latchman DS. Source: Journal of Immunological Methods. 2002 December 15; 270(2): 235-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379328&dopt=Abstract
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Oral mucosal herpes simplex ulceration in an HIV-seropositive man. Author(s): Phelan JA, Kerpel SM, Freedman PD. Source: Aids Read. 1999 January-February; 9(1): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728881&dopt=Abstract
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Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients. Author(s): Liesveld JL, Abboud CN, Ifthikharuddin JJ, Lancet JE, Wedow LA, Oliva J, Stamm CG, Nichols D. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2002; 8(12): 662-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523578&dopt=Abstract
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Overproduction of gamma interferon in B/Jas inbred rabbits with herpes simplex virus encephalitis. Author(s): Yuasa T, Isono T, Tooyama I, Seto A. Source: Microbiology and Immunology. 1999; 43(4): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10385203&dopt=Abstract
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Pathologic quiz case: multiple foci of necrosis in the liver in a patient with T-cell lymphoma. Herpes simplex virus hepatitis. Author(s): Tan G, Frankel WL, Suster S. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 1049-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873187&dopt=Abstract
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Phenotypic and genotypic methods for the detection of herpes simplex virus serotypes. Author(s): Madhavan HN, Priya K, Bagyalakshmi R. Source: Journal of Virological Methods. 2003 March; 108(1): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565159&dopt=Abstract
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PML residue lysine 160 is required for the degradation of PML induced by herpes simplex virus type 1 regulatory protein ICP0. Author(s): Boutell C, Orr A, Everett RD. Source: Journal of Virology. 2003 August; 77(16): 8686-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885887&dopt=Abstract
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Postinfectious autoimmune-mediated encephalitis eight months after herpes simplex encephalitis. Author(s): Joos AA, Ziyeh S, Rauer S, Keller E, Huzly D, Lucking CH. Source: European Neurology. 2003; 50(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824714&dopt=Abstract
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Potentiated gene delivery to tumors using herpes simplex virus/Epstein-Barr virus/RV tribrid amplicon vectors. Author(s): Hampl JA, Camp SM, Mydlarz WK, Hampl M, Ichikawa T, Chiocca EA, Louis DN, Sena-Esteves M, Breakefield XO. Source: Human Gene Therapy. 2003 May 1; 14(7): 611-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804144&dopt=Abstract
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Prevalence of herpes simplex virus antibodies in childhood and adolescence: a crosssectional study. Author(s): Tunback P, Bergstrom T, Andersson AS, Nordin P, Krantz I, Lowhagen GB. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(8): 498-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514152&dopt=Abstract
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Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis. Author(s): Lairson DR, Begley CE, Reynolds TF, Wilhelmus KR. Source: Archives of Ophthalmology. 2003 January; 121(1): 108-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523894&dopt=Abstract
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Problems in the use of herpes simplex virus as a vector. Author(s): Feldman LT. Source: Int Rev Neurobiol. 2003; 55: 99-109. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968532&dopt=Abstract
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Protection by herpes simplex virus glycoprotein D against Fas-mediated apoptosis: role of nuclear factor kappaB. Author(s): Medici MA, Sciortino MT, Perri D, Amici C, Avitabile E, Ciotti M, Balestrieri E, De Smaele E, Franzoso G, Mastino A. Source: The Journal of Biological Chemistry. 2003 September 19; 278(38): 36059-67. Epub 2003 July 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844494&dopt=Abstract
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Psychosocial impact of serological diagnosis of herpes simplex virus type 2: a qualitative assessment. Author(s): Melville J, Sniffen S, Crosby R, Salazar L, Whittington W, Dithmer-Schreck D, DiClemente R, Wald A. Source: Sexually Transmitted Infections. 2003 August; 79(4): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902574&dopt=Abstract
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Quantitation of herpes simplex DNA in blood during aciclovir therapy with competitive PCR ELISA. Author(s): Bezold G, Gottlober P, Leiter U, Kerscher M, Krahn G, Peter RU. Source: Dermatology (Basel, Switzerland). 2000; 201(4): 296-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146337&dopt=Abstract
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Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia. Author(s): Pevenstein SR, Williams RK, McChesney D, Mont EK, Smialek JE, Straus SE. Source: Journal of Virology. 1999 December; 73(12): 10514-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559370&dopt=Abstract
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Quantitation of viral load in neonatal herpes simplex virus infection and comparison between type 1 and type 2. Author(s): Kimura H, Ito Y, Futamura M, Ando Y, Yabuta Y, Hoshino Y, Nishiyama Y, Morishima T. Source: Journal of Medical Virology. 2002 July; 67(3): 349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116026&dopt=Abstract
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Reactivation of herpes simplex keratitis during TL01 phototherapy for psoriasis. Author(s): Wong GA, Kaye SB, Parslew R. Source: Clinical and Experimental Dermatology. 2003 July; 28(4): 453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823318&dopt=Abstract
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Recent progress in herpes simplex virus immunobiology and vaccine research. Author(s): Koelle DM, Corey L. Source: Clinical Microbiology Reviews. 2003 January; 16(1): 96-113. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525427&dopt=Abstract
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Recurrent dermatomal vesicular skin lesions: a clue to diagnosis of herpes simplex virus 2 meningitis. Author(s): Gonzales N, Tyler KL, Gilden DH. Source: Archives of Neurology. 2003 June; 60(6): 868-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810492&dopt=Abstract
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Recurrent herpes simplex labialis: selected therapeutic options. Author(s): Raborn GW, Grace MG. Source: Journal (Canadian Dental Association). 2003 September; 69(8): 498-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954137&dopt=Abstract
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Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation. Author(s): Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 February; 74(2): 2624. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531966&dopt=Abstract
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Replication and interaction of herpes simplex virus and human papillomavirus in differentiating host epithelial tissue. Author(s): Meyers C, Andreansky SS, Courtney RJ. Source: Virology. 2003 October 10; 315(1): 43-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592758&dopt=Abstract
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Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway. Author(s): Eom CY, Lehman IR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 9803-7. Epub 2003 Aug 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904574&dopt=Abstract
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Resolution of psychiatric symptoms secondary to herpes simplex encephalitis. Author(s): Gaber TA, Eshiett M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 August; 74(8): 1164; Author Reply 1164. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876271&dopt=Abstract
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Risk factors for infection with herpes simplex virus type 2: role of smoking, douching, uncircumcised males, and vaginal flora. Author(s): Cherpes TL, Meyn LA, Krohn MA, Hillier SL. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916131&dopt=Abstract
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RNAs extracted from herpes simplex virus 1 virions: apparent selectivity of viral but not cellular RNAs packaged in virions. Author(s): Sciortino MT, Suzuki M, Taddeo B, Roizman B. Source: Journal of Virology. 2001 September; 75(17): 8105-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483756&dopt=Abstract
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Schizophreniform disorder with cerebrospinal fluid PCR positivity for herpes simplex virus type 1. Author(s): Chiveri L, Sciacco M, Prelle A. Source: European Neurology. 2003; 50(3): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530627&dopt=Abstract
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Secreted portion of glycoprotein g of herpes simplex virus type 2 is a novel antigen for type-discriminating serology. Author(s): Gorander S, Svennerholm B, Liljeqvist JA. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3681-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904375&dopt=Abstract
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Seroprevalence and correlates of herpes simplex virus type 2 among urban Tanzanian women. Author(s): Msuya SE, Mbizvo E, Hussain A, Sam NE, Jeansson S, Stray-Pedersen B. Source: Sexually Transmitted Diseases. 2003 July; 30(7): 588-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838089&dopt=Abstract
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Sero-prevalence of Herpes simplex virus type 2 (HSV-2) in Rakai district, Uganda. Author(s): Emonyi IW, Gray RH, Zenilman J, Schmidt K, Wawer MJ, Sewankambo KN, Serwadda D, Kiwanuka N, Nalugoda F. Source: East Afr Med J. 2000 August; 77(8): 428-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862067&dopt=Abstract
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Sexual and demographic risk factors for herpes simplex virus type 2 according to schooling level among Mexican youths. Author(s): Abraham CD, Conde-Glez CJ, Cruz-Valdez A, Sanchez-Zamorano L, Hernandez-Marquez C, Lazcano-Ponce E. Source: Sexually Transmitted Diseases. 2003 July; 30(7): 549-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838082&dopt=Abstract
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Socio-demographic characteristics and sex practices related to herpes simplex virus type 2 infection in Mexican and Central American female sex workers. Author(s): Uribe-Salas F, Conde-Glez CJ, Juarez-Figueroa L, Hernandez-Castellanos A. Source: Epidemiology and Infection. 2003 October; 131(2): 859-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14596526&dopt=Abstract
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Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry. Author(s): Bender FC, Whitbeck JC, Ponce de Leon M, Lou H, Eisenberg RJ, Cohen GH. Source: Journal of Virology. 2003 September; 77(17): 9542-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915568&dopt=Abstract
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Structure-based mutagenesis of herpes simplex virus glycoprotein D defines three critical regions at the gD-HveA/HVEM binding interface. Author(s): Connolly SA, Landsburg DJ, Carfi A, Wiley DC, Cohen GH, Eisenberg RJ. Source: Journal of Virology. 2003 July; 77(14): 8127-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829851&dopt=Abstract
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Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection. Author(s): Fang L, Ward MG, Welsh PA, Budgeon LR, Neely EB, Howett MK. Source: Virology. 2003 September 15; 314(1): 147-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517068&dopt=Abstract
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Sweet's syndrome associated with Mycobacterium chelonae and herpes simplex virus infections: a case report. Author(s): Theng TS, Chan YC, Leow YH, Tan SH. Source: Ann Acad Med Singapore. 2003 May; 32(3): 411-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854387&dopt=Abstract
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Tetracycline-regulated gene expression in replication-incompetent herpes simplex virus vectors. Author(s): Schmeisser F, Donohue M, Weir JP. Source: Human Gene Therapy. 2002 December 10; 13(18): 2113-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542843&dopt=Abstract
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The degradation of promyelocytic leukemia and Sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme UbcH5a. Author(s): Gu H, Roizman B. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 22; 100(15): 8963-8. Epub 2003 Jul 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855769&dopt=Abstract
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The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis. Author(s): Anglen CS, Truckenmiller ME, Schell TD, Bonneau RH. Source: Journal of Neuroimmunology. 2003 July; 140(1-2): 13-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864968&dopt=Abstract
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The gene that encodes the herpes simplex virus type 1 latency-associated transcript influences the accumulation of transcripts (Bcl-x(L) and Bcl-x(S)) that encode apoptotic regulatory proteins. Author(s): Peng W, Henderson G, Perng GC, Nesburn AB, Wechsler SL, Jones C. Source: Journal of Virology. 2003 October; 77(19): 10714-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970460&dopt=Abstract
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The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and Ubiquitinates p53. Author(s): Boutell C, Everett RD. Source: The Journal of Biological Chemistry. 2003 September 19; 278(38): 36596-602. Epub 2003 July 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855695&dopt=Abstract
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The interaction between dendritic cells and herpes simplex virus-1. Author(s): Kobelt D, Lechmann M, Steinkasserer A. Source: Curr Top Microbiol Immunol. 2003; 276: 145-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797447&dopt=Abstract
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The prevalence of Herpes simplex virus type-2 infection in blood donors in Harare, Zimbabwe. Author(s): Gwanzura L, Chigonda TG, Mvere D, De Villiers DM, Siziya S, Mason PR. Source: Cent Afr J Med. 2002 March-April; 48(3-4): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971156&dopt=Abstract
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The R1 subunit of herpes simplex virus ribonucleotide reductase has chaperone-like activity similar to Hsp27. Author(s): Chabaud S, Lambert H, Sasseville AM, Lavoie H, Guilbault C, Massie B, Landry J, Langelier Y. Source: Febs Letters. 2003 June 19; 545(2-3): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804778&dopt=Abstract
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The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer. Author(s): Stiles BM, Bhargava A, Adusumilli PS, Stanziale SF, Kim TH, Rusch VW, Fong Y. Source: Surgery. 2003 August; 134(2): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947341&dopt=Abstract
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Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. Author(s): Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Source: The Journal of Experimental Medicine. 2003 August 4; 198(3): 513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900525&dopt=Abstract
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Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids. Author(s): Reynolds AE, Wills EG, Roller RJ, Ryckman BJ, Baines JD. Source: Journal of Virology. 2002 September; 76(17): 8939-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163613&dopt=Abstract
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Uncontrolled herpes simplex virus-2 as a cofactor in HIV transmission. Author(s): Gisselquist D, Potterat JJ. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 May 1; 33(1): 119-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792367&dopt=Abstract
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Unilateral acute retinal necrosis occurring 2 years after herpes simplex type 1 encephalitis. Author(s): Kim C, Yoon YH. Source: Ophthalmic Surgery and Lasers. 2002 May-June; 33(3): 250-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027110&dopt=Abstract
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Unusual herpes simplex virus infection mimicking foreign body reaction after cosmetic lip augmentation with expanded polytetrafluoroethylene threads. Author(s): Rudolph CM, Mullegger RR, Schuller-Petrovic S, Kerl H, Soyer HP. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 February; 29(2): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562355&dopt=Abstract
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Unusual, rapidly growing ulcerative genital mass due to herpes simplex virus in a human immunodeficiency virus-infected woman. Author(s): Lanzafame M, Mazzi R, Di Pace C, Trevenzoli M, Concia E, Vento S. Source: The British Journal of Dermatology. 2003 July; 149(1): 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890233&dopt=Abstract
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Use of a single monoclonal antibody to determine the susceptibilities of herpes simplex virus type 1 and type 2 clinical isolates to acyclovir. Author(s): Chutkowski C, Olson B, McDonough A, Mahoney J, McSharry JJ. Source: Clinical and Diagnostic Laboratory Immunology. 2002 November; 9(6): 1379-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414779&dopt=Abstract
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Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer. Author(s): Coukos G, Makrigiannakis A, Kang EH, Caparelli D, Benjamin I, Kaiser LR, Rubin SC, Albelda SM, Molnar-Kimber KL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 June; 5(6): 1523-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389942&dopt=Abstract
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Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. Author(s): Pyles RB, Higgins D, Chalk C, Zalar A, Eiden J, Brown C, Van Nest G, Stanberry LR. Source: Journal of Virology. 2002 November; 76(22): 11387-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388699&dopt=Abstract
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Use of the herpes simplex viral genome to construct gene therapy vectors. Author(s): Burton EA, Huang S, Goins WF, Glorioso JC. Source: Methods in Molecular Medicine. 2003; 76: 1-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526156&dopt=Abstract
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Use of the highly sensitive PCR method to detect the Herpes simplex virus type 1 genome and its expression in samples from Behcet disease patients. Author(s): Nomura Y, Kitteringham N, Shiba K, Goseki M, Kimura A, Mineshita S. Source: J Med Dent Sci. 1998 March; 45(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160245&dopt=Abstract
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Val193 and Phe195 of the gamma 1 34.5 protein of herpes simplex virus 1 are required for viral resistance to interferon-alpha/beta. Author(s): Cheng G, Brett ME, He B. Source: Virology. 2001 November 10; 290(1): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882996&dopt=Abstract
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Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials. Author(s): Conant MA, Schacker TW, Murphy RL, Gold J, Crutchfield LT, Crooks RJ; International Valaciclovir HSV Study Group. Source: International Journal of Std & Aids. 2002 January; 13(1): 12-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802924&dopt=Abstract
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Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir. Author(s): Tyring SK, Baker D, Snowden W. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S40-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353186&dopt=Abstract
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Valacyclovir in the treatment of facial herpes simplex virus infection. Author(s): Laiskonis A, Thune T, Neldam S, Hiltunen-Back E. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353189&dopt=Abstract
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Valacyclovir prophylaxis for herpes simplex virus infection or infection recurrence following laser skin resurfacing. Author(s): Beeson WH, Rachel JD. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 April; 28(4): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966791&dopt=Abstract
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Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation. Author(s): Dignani MC, Mykietiuk A, Michelet M, Intile D, Mammana L, Desmery P, Milone G, Pavlovsky S. Source: Bone Marrow Transplantation. 2002 February; 29(3): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859400&dopt=Abstract
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Viral infections of the CNS with special emphasis on herpes simplex infections. Author(s): Schmutzhard E. Source: Journal of Neurology. 2001 June; 248(6): 469-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499636&dopt=Abstract
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Viremia in neonatal herpes simplex virus infections. Author(s): Diamond C, Mohan K, Hobson A, Frenkel L, Corey L. Source: The Pediatric Infectious Disease Journal. 1999 June; 18(6): 487-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391175&dopt=Abstract
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Visual outcome in herpes simplex virus and varicella zoster virus uveitis: a clinical evaluation and comparison. Author(s): Miserocchi E, Waheed NK, Dios E, Christen W, Merayo J, Roque M, Foster CS. Source: Ophthalmology. 2002 August; 109(8): 1532-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153807&dopt=Abstract
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Voxel-based morphometry of herpes simplex encephalitis. Author(s): Gitelman DR, Ashburner J, Friston KJ, Tyler LK, Price CJ. Source: Neuroimage. 2001 April; 13(4): 623-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305891&dopt=Abstract
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What triggers recurrences of herpes simplex keratitis. Author(s): Raizman MB. Source: Archives of Ophthalmology. 2000 December; 118(12): 1682. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115264&dopt=Abstract
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What's your assessment? The diagnosis is herpes simplex. Author(s): Bielan B. Source: Dermatology Nursing / Dermatology Nurses' Association. 1999 April; 11(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10670331&dopt=Abstract
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Why do we lack an effective vaccine against herpes simplex virus infections? Author(s): Deshpande SP, Kumaraguru U, Rouse BT. Source: Microbes and Infection / Institut Pasteur. 2000 July; 2(8): 973-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962281&dopt=Abstract
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Wild-type herpes simplex virus 1 blocks programmed cell death and release of cytochrome c but not the translocation of mitochondrial apoptosis-inducing factor to the nuclei of human embryonic lung fibroblasts. Author(s): Zhou G, Roizman B. Source: Journal of Virology. 2000 October; 74(19): 9048-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982349&dopt=Abstract
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Will taking the amino acid supplement lysine prevent or treat the herpes simplex virus? Author(s): Marcason W. Source: Journal of the American Dietetic Association. 2003 March; 103(3): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616258&dopt=Abstract
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You're the flight surgeon. Herpes simplex virus type 2(HSV-2). Author(s): Fisher CR Jr. Source: Aviation, Space, and Environmental Medicine. 1999 April; 70(4): 351-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10223273&dopt=Abstract
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Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Author(s): Lu R, Misra V. Source: Nucleic Acids Research. 2000 June 15; 28(12): 2446-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871379&dopt=Abstract
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CHAPTER 2. NUTRITION AND HERPES SIMPLEX Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and herpes simplex.
Finding Nutrition Studies on Herpes Simplex The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “herpes simplex” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “herpes simplex” (or a synonym): •
A cell type-specific and gap junction-independent mechanism for the herpes simplex virus-1 thymidine kinase gene/ganciclovir-mediated bystander effect. Author(s): Laboratory of Medical Chemistry and Medical Oncology, University of Liege, Belgium. Source: Princen, F Robe, P Lechanteur, C Mesnil, M Rigo, J M Gielen, J Merville, M P Bours, V Clin-Cancer-Res. 1999 November; 5(11): 3639-44 1078-0432
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A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis. Author(s): Department of Neurology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
[email protected] Source: Ben Hur, T Cialic, R Itzik, A Barak, O Yirmiya, R Weidenfeld, J Neuroscience. 2001; 108(1): 119-27 0306-4522
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Aborted genital herpes simplex virus lesions: findings from a randomised controlled trial with valaciclovir. Author(s): Department of Dermatology and Venereology, University Hospital, Uppsala, Sweden.
[email protected] Source: Strand, A Patel, R Wulf, H C Coates, K M Sex-Transm-Infect. 2002 December; 78(6): 435-9 1368-4973
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Activities of Korean medicinal herbs and traditional prescriptions against Herpes simplex virus type-1. Source: Kang, B.J. Lee, H.H. Kim, N.J. Kong, W.S. Park, K.J. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. October 1998. volume 36 (4) page 287-294. 1388-0209
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AlaArg motif in the carboxyl terminus of the gamma(1)34.5 protein of herpes simplex virus type 1 is required for the formation of a high-molecular-weight complex that dephosphorylates eIF-2alpha. Author(s): Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, Chicago, Illinois 60612, USA. Source: Cheng, G Gross, M Brett, M E He, B J-Virol. 2001 April; 75(8): 3666-74 0022-538X
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Anti-herpes simplex virus effect of an aqueous extract of propolis. Author(s): Institute for Applied Biosciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
[email protected] Source: Huleihel, M Isanu, V Isr-Med-Assoc-J. 2002 November; 4(11 Suppl): 923-7 15651088
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Antiviral activity of characterized extracts from echinacea spp. (Heliantheae: Asteraceae) against herpes simplex virus (HSV-I). Author(s): Department of Biology, University of Ottawa, Ottawa, Canada. Source: Binns, S E Hudson, J Merali, S Arnason, J T Planta-Med. 2002 September; 68(9): 780-3 0032-0943
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Asymptomatic shedding of herpes simplex virus into the oral cavity of patients with atopic dermatitis. Author(s): Department of Dermatology, School of Medicine, Kinki University, Osaka, Japan. Source: Yoshida, M Amatsu, A J-Clin-Virol. 2000 February; 16(1): 65-9 1386-6532
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Characterization and transduction of a retroviral vector encoding human interleukin4 and herpes simplex virus-thymidine kinase for glioma tumor vaccine therapy. Author(s): Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
[email protected] Source: Okada, H Attanucci, J Tahara, H Pollack, I F Bozik, M E Chambers, W H Lotze, M T Cancer-Gene-Ther. 2000 March; 7(3): 486-94 0929-1903
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Characterization of RNA determinants recognized by the arginine- and proline-rich region of Us11, a herpes simplex virus type 1-encoded double-stranded RNA binding protein that prevents PKR activation. Author(s): Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA. Source: Khoo, D Perez, C Mohr, I J-Virol. 2002 December; 76(23): 11971-81 0022-538X
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Comparative bioavailability of acyclovir from oral valacyclovir and acyclovir in patients treated for recurrent genital herpes simplex virus infection. Author(s): Department of Pharmacology, University of Manitoba, Winnipeg, Canada. Source: Bras, A P Sitar, D S Aoki, F Y Can-J-Clin-Pharmacol. 2001 Winter; 8(4): 207-11 1198-581X
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Comparison of microbicides for efficacy in protecting mice against vaginal challenge with herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization. Author(s): Population Council, New York, New York 10021, USA. Source: Maguire, R A Bergman, N Phillips, D M Sex-Transm-Dis. 2001 May; 28(5): 25965 0148-5717
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Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system. Author(s): Department of Virology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
[email protected] Source: Hayashi, Kyoko Hayashi, Toshimitsu Sun, Han Dong Takeda, Yoshio HumGene-Ther. 2002 February 10; 13(3): 415-23 1043-0342
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Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated from Euphorbia species. Source: Mucsi, I. Molnar, J. Hohmann, J. Redei, D. Planta-med. Stuttgart : Georg Thieme Verlag,. October 2001. volume 67 (7) page 672-674. 0032-0943
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Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1. Author(s): Division of Molecular Psychiatry, Center for Genes and Behavior, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.
[email protected] Source: Carlezon, W A Haile, C N Coppersmith, R Hayashi, Y Malinow, R Neve, R L Nestler, E J J-Neurosci. 2000 March 1; 20(5): RC62 1529-2401
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Early therapy with valaciclovir or famciclovir reduces but does not abrogate herpes simplex virus neuronal latency. Author(s): Centre for Veterinary Science, Cambridge University Veterinary School. Source: Field, H J Thackray, A M Nucleosides-Nucleotides-Nucleic-Acids. 2000 JanFebruary; 19(1-2): 461-70 1525-7770
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Enhancement of the herpes simplex virus thymidine kinase/ganciclovir bystander effect and its antitumor efficacy in vivo by pharmacologic manipulation of gap junctions. Author(s): Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Source: Touraine, R L Vahanian, N Ramsey, W J Blaese, R M Hum-Gene-Ther. 1998 November 1; 9(16): 2385-91 1043-0342
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Environmental influence on immune inhibition of release of herpes simplex virus from cells. Author(s): Department of Infection, Medical School, University of Birmingham, Birmingham, UK.
[email protected] Source: Benitez, J Ahmad, A Davies, J Skinner, G R Intervirology. 1998; 41(2-3): 120-6 0300-5526
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Establishment of a quiescent herpes simplex virus type 1 infection in neurallydifferentiated PC12 cells. Author(s): Department of Oral Health Practice, University of Kentucky College of Dentistry, Lexington 40536-0084, USA. Source: Danaher, R J Jacob, R J Miller, C S J-Neurovirol. 1999 June; 5(3): 258-67 1355-0284
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Expression of herpes simplex virus glycoprotein B gene in yeast. Source: Nozaki, C. Makizumi, K. Kino, Y. Nakatake, H. Eto, T. Mizuno, K. Hamada, F. Ohtomo, N. Virus-Res. Amsterdam : Elsevier Science Publishers B.V. December 1985. volume 4 (1) page 107-113. 0168-1702
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Gene therapy of bladder pain with herpes simplex virus (HSV) vectors expressing preproenkephalin (PPE). Author(s): Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Source: Yoshimura, N Franks, M E Sasaki, K Goins, W F Goss, J Yokoyama, T Fraser, M O Seki, S Fink, J Glorioso, J de Groat, W C Chancellor, M B Urology. 2001 June; 57(6 Suppl 1): 116 1527-9995
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Genital herpes simplex virus infection in the adolescent: special considerations for management. Author(s): Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0351, USA.
[email protected] Source: Stanberry, L R Rosenthal, S L Paediatr-Drugs. 2002; 4(5): 291-7 1174-5878
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Heat stress activates production of herpes simplex virus type 1 from quiescently infected neurally differentiated PC12 cells. Author(s): Department of Oral Health Practice, University of Kentucky College of Dentistry, Lexington 40536-0297, USA. Source: Danaher, R J Jacob, R J Chorak, M D Freeman, C S Miller, C S J-Neurovirol. 1999 August; 5(4): 374-83 1355-0284
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Herpes simplex virus infection. Author(s): Department of Pediatrics, University of Alabama at Birmingham, USA.
[email protected] Source: Whitley, R J Semin-Pediatr-Infect-Dis. 2002 January; 13(1): 6-11 1045-1870
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Histologic and immunohistochemical analysis of tissue response to adenovirusmediated herpes simplex thymidine kinase gene therapy of ovarian cancer. Author(s): Department of Obstetrics and Gynecology, Freiburg University Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
[email protected] Source: Hasenburg, A Fischer, D C Tong, X W Rojas Martinez, A Nyberg Hoffman, C Orlowska Volk, M Kohlberger, P Kaufman, R H Ramzy, I Aguilar Cordova, E Kieback, D G Int-J-Gynecol-Cancer. 2002 Jan-February; 12(1): 66-73 1048-891X
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Hydroxyurea significantly enhances tumor growth delay in vivo with herpes simplex virus thymidine kinase/ganciclovir gene therapy. Author(s): Department of Pharmacology, University of Michigan Medical Center, Ann Arbor 48109-0504, USA. Source: Boucher, P D Ostruszka, L J Murphy, P J M Shewach, D S Gene-Ther. 2002 August; 9(15): 1023-30 0969-7128
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ICP27 interacts with the RNA export factor Aly/REF to direct herpes simplex virus type 1 intronless mRNAs to the TAP export pathway. Author(s): Department of Microbiology and Molecular Genetics, Medical Sciences I, College of Medicine, University of California, Irvine, CA 92697-4025, USA. Source: Chen, I H Sciabica, K S Sandri Goldin, R M J-Virol. 2002 December; 76(24): 12877-89 0022-538X
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In vitro antiviral effect of flavonoid-rich extracts of Vitex polygama (Verbenaceae) against acyclovir-resistant herpes simplex virus type 1. Author(s): Instituto de Microbiologia Professor Paulo de Goes, Departamento de Virologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Source: Goncalves, J L Leitao, S G Monache, F D Miranda, M M Santos, M G Romanos, M T Wigg, M D Phytomedicine. 2001 November; 8(6): 477-80 0944-7113
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Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1. Author(s): Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA. Source: Aubert, M O'Toole, J Blaho, J A J-Virol. 1999 December; 73(12): 10359-70 0022538X
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Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell transplantation. Author(s): Unite mixte de recherche 7565 UHP-CNRS, laboratoire de bacteriologievirologie, faculte de medecine, Vandoeuvre-les-Nancy, France.
[email protected] Source: Venard, V Dauendorffer, J N Carret, A S Corsaro, D Edert, D Bordigoni, P Le Faou, A Pathol-Biol-(Paris). 2001 September; 49(7): 553-8 0369-8114
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Infection of human NT2 cells and differentiated NT-neurons with herpes simplex virus and replication-incompetent herpes simplex virus vectors. Author(s): Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Source: Weir, J P J-Neurovirol. 2001 February; 7(1): 43-51 1355-0284
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Inhibitory effect of anti-pyretic and anti-inflammatory herbs on herpes simplex virus replication. Author(s): Department of Microbiology, China Medical College, Taichung, Taiwan. Source: Hsiang, C Y Hsieh, C L Wu, S L Lai, I L Ho, T Y Am-J-Chin-Med. 2001; 29(3-4): 459-67 0192-415X
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Interleukin-18 protects mice against acute herpes simplex virus type 1 infection. Author(s): Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan. Source: Fujioka, N Akazawa, R Ohashi, K Fujii, M Ikeda, M Kurimoto, M J-Virol. 1999 March; 73(3): 2401-9 0022-538X
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Interrelation of diet and herpes simplex virus pathogenesis in mice. Source: Fischer, K.J. Wright, S.M. Kelleher, J.J. Proc-N-D-Acad-Sci. Grand Forks, N.D. : The Academy. April 1988. volume 42 page 48. 0096-9214
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Local periocular vaccination protects against eye disease more effectively than systemic vaccination following primary ocular herpes simplex virus infection in rabbits. Author(s): Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, California, USA. Source: Nesburn, A B Slanina, S Burke, R L Ghiasi, H Bahri, S Wechsler, S L J-Virol. 1998 October; 72(10): 7715-21 0022-538X
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Mapping of functional regions in the amino-terminal portion of the herpes simplex virus ICP27 regulatory protein: importance of the leucine-rich nuclear export signal and RGG Box RNA-binding domain. Author(s): Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. Source: Lengyel, J Guy, C Leong, V Borge, S Rice, S A J-Virol. 2002 December; 76(23): 11866-79 0022-538X
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Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes simplex virus type 1 and 2. Author(s): Institute of Microbiology, University of Rome La Sapienza, Italy. Source: Marchetti, M Pisani, S Antonini, G Valenti, P Seganti, L Orsi, N Biometals. 1998 April; 11(2): 89-94 0966-0844
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Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein. Author(s): Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA. Source: Kotsakis, A Pomeranz, L E Blouin, A Blaho, J A J-Virol. 2001 September; 75(18): 8697-711 0022-538X
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Mitochondrial distribution and function in herpes simplex virus-infected cells. Author(s): Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 4668550, Japan. Source: Murata, T Goshima, F Daikoku, T Inagaki Ohara, K Takakuwa, H Kato, K Nishiyama, Y J-Gen-Virol. 2000 February; 81 Pt 2401-6 0022-1317
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Morphine reduces herpes simplex virus-1 pathogenesis in the murine flank. Author(s): Adelphi University, Division of Science and Mathematics, Department of Biology, Garden City, NY 11530, USA.
[email protected] Source: Weeks, B S Alston, N I Cadet, P Zhu, W Rialas, C Stefano, G B Int-J-Mol-Med. 2001 September; 8(3): 303-7 1107-3756
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Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice. Author(s): Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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Source: Luker, G D Bardill, J P Prior, J L Pica, C M Piwnica Worms, D Leib, D A J-Virol. 2002 December; 76(23): 12149-61 0022-538X •
Nuclear and nucleolar localization of an African swine fever virus protein, I14L, that is similar to the herpes simplex virus-encoded virulence factor ICP34.5. Source: Goatley, L.C. Marron, M.B. Jacobs, S.C. Hammond, J.M. Miskin, J.E. Abrams, C.C. Smith, G.L. Dixon, L.K. J-gen-virol. Reading : Society for General Microbiology. Mar 1999. volume 80 (pt.3) page 525-535. 0022-1317
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Ocular herpes simplex. Author(s): Specialist Eye Centre, Christ Church, Barbados. Source: Barker, N Clin-Evid. 2002 June; (7): 597-604 1462-3846
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Plant extracts antiviral activity against Herpes simplex virus type 1 and African swine fever virus. Source: Silva, O. Barbosa, S. Diniz, A. Valdeira, M.L. Gomes, E. Int-j-pharmacogn. Lisse, Netherlands : Swets & Zeitlinger B.V., 1991-. January 1997. volume 35 (1) page 12-16. 0925-1618
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Properties and evolutionary relationships of the Marek's disease virus homologues of protein kinase, glycoprotein D and glycoprotein I of herpes simplex virus. Source: Ross, L.J.N. Binns, M.M. J-Gen-Virol. Reading : Society for General Microbiology. April 1991. volume 72 (pt.4) page 939-947. 0022-1317
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Recurrent herpes simplex virus infection. Suppressive, reactive, and preventive antiviral regimens. Author(s): Forum Health, Northside Medical Center, Youngstown, Ohio, USA. Source: Guerriere Kovach, P M Brodell, R T Postgrad-Med. 2000 May 15; 107(6): 139-40, 143, 147 0032-5481
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Regions of the herpes simplex virus type 1 latency-associated transcript that protect cells from apoptosis in vitro and protect neuronal cells in vivo. Author(s): Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. Source: Ahmed, Maryam Lock, Martin Miller, Cathie G Fraser, Nigel W J-Virol. 2002 January; 76(2): 717-29 0022-538X
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Signals that dictate nuclear, nucleolar, and cytoplasmic shuttling of the gamma(1)34.5 protein of herpes simplex virus type 1. Author(s): Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, Chicago, Illinois 60612, USA. Source: Cheng, G Brett, M E He, B J-Virol. 2002 September; 76(18): 9434-45 0022-538X
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Studies on the constituents of seeds of Pachyrrhizus erosus and their anti herpes simplex virus (HSV) activities. Author(s): Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. Source: Phrutivorapongkul, A Lipipun, V Ruangrungsi, N Watanabe, T Ishikawa, T Chem-Pharm-Bull-(Tokyo). 2002 April; 50(4): 534-7 0009-2363
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Subcellular localization of herpes simplex virus type 1 UL51 protein and role of palmitoylation in Golgi apparatus targeting. Author(s): Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8550, Japan. Source: Nozawa, N Daikoku, T Koshizuka, T Yamauchi, Y Yoshikawa, T Nishiyama, Y JVirol. 2003 March; 77(5): 3204-16 0022-538X
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Synergy between the herpes simplex virus tk/ganciclovir prodrug suicide system and the topoisomerase I inhibitor topotecan. Author(s): Clinical Gene Therapy Branch/National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1851, USA.
[email protected] Source: Wildner, O Blaese, R M Morris, J C Hum-Gene-Ther. 1999 November 1; 10(16): 2679-87 1043-0342
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T lymphocyte transduction with herpes simplex virus-thymidine kinase (HSV-tk) gene: comparison of four different infection protocols. Author(s): Department of Clinical and Experimental Medicine, Perugia University, Italy. Source: Di Ianni, M Di Florio, S Venditti, G Falzetti, F Mannoni, P Martelli, M F Tabilio, A J-Hematother-Stem-Cell-Res. 1999 December; 8(6): 645-52 1525-8165
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The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway. Author(s): Departments of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. Source: Perkins, D Pereira, E F R Gober, M Yarowsky, P J Aurelian, L J-Virol. 2002 February; 76(3): 1435-49 0022-538X
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The regulation of burn-associated infections with herpes simplex virus type 1 or Candida albicans by a non-toxic aconitine-hydrolysate, benzoylmesaconine. Part 1: Antiviral and anti-fungal activities in thermally injured mice. Author(s): Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0835, USA. Source: Kobayashi, M Mori, K Kobayashi, H Pollard, R B Suzuki, F Immunol-Cell-Biol. 1998 June; 76(3): 202-8 0818-9641
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Two-drug combinations that increase apoptosis and modulate bak and bcl-X(L) expression in human colon tumor cell lines transduced with herpes simplex virus thymidine kinase. Author(s): Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. Source: McMasters, R A Wilbert, T N Jones, K E Pitlyk, K Saylors, R L Moyer, M P Chambers, T C Drake, R R Cancer-Gene-Ther. 2000 April; 7(4): 563-73 0929-1903
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Ultraviolet-B radiation induces modulation of antigen presentation of herpes simplex virus by human epidermal cells. Author(s): Center for Electron Microscopy, Leiden University Medical Center, Leiden, The Netherlands.
[email protected] Source: van der Molen, R G Out Luiting, C Claas, F H Norval, M Koerten, H K Mommaas, A M Hum-Immunol. 2001 June; 62(6): 589-97 0198-8859
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Use of oral valaciclovir in a 12-year-old boy with herpes simplex encephalitis. Author(s): Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. Source: Chan, P K Chow, P C Peiris, J S Mak, A W Huen, K F Hong-Kong-Med-J. 2000 March; 6(1): 119-21 1024-2708
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Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials. Author(s): University of California San Francisco Medical Center, San Francisco, CA 94143, USA. Source: Conant, M A Schacker, T W Murphy, R L Gold, J Crutchfield, L T Crooks, R J Int-J-STD-AIDS. 2002 January; 13(1): 12-21 0956-4624
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Valacyclovir inhibition of recovery of ocular herpes simplex virus type 1 after experimental reactivation by laser in situ keratomileusis. Author(s): Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15203, USA.
[email protected] Source: Dhaliwal, D K Romanowski, E G Yates, K A Hu, D Mah, F S Fish, D N Gordon, Y J J-Cataract-Refract-Surg. 2001 August; 27(8): 1288-93 0886-3350
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Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation. Author(s): Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. Source: Dignani, M C Mykietiuk, A Michelet, M Intile, D Mammana, L Desmery, P Milone, G Pavlovsky, S Bone-Marrow-Transplant. 2002 February; 29(3): 263-7 0268-3369
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to herpes simplex; 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
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Minerals Quercetin Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet Chocolate Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND HERPES SIMPLEX Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to herpes simplex. 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 herpes simplex 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 “herpes simplex” (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 herpes simplex: •
A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV). Author(s): Vynograd N, Vynograd I, Sosnowski Z. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2000 March; 7(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782483&dopt=Abstract
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A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Author(s): Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, Iyer M, Namavari M, Phelps ME, Herschman HR.
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Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 March 14; 97(6): 2785-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716999&dopt=Abstract •
An antiviral principle present in a purified fraction from Melia azedarach L. leaf aqueous extract restrains herpes simplex virus type 1 propagation. Author(s): Alche LE, Barquero AA, Sanjuan NA, Coto CE. Source: Phytotherapy Research : Ptr. 2002 June; 16(4): 348-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112291&dopt=Abstract
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Anti-Herpes simplex virus activity of Bidens pilosa and Houttuynia cordata. Author(s): Chiang LC, Chang JS, Chen CC, Ng LT, Lin CC. Source: The American Journal of Chinese Medicine. 2003; 31(3): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943167&dopt=Abstract
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Anti-herpes simplex virus effect of a seed extract from the tropical plant Licania tomentosa (Benth.) Fritsch (Chrysobalanaceae). Author(s): Miranda MM, Goncalves JL, Romanos MT, Silva FP, Pinto L, Silva MH, Ejzemberg R, Granja LF, Wigg MD. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 October; 9(7): 641-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487329&dopt=Abstract
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Anti-herpes simplex virus effect of an aqueous extract of propolis. Author(s): Huleihel M, Isanu V. Source: Isr Med Assoc J. 2002 November; 4(11 Suppl): 923-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455181&dopt=Abstract
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Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Author(s): Cheng HY, Lin CC, Lin TC. Source: Antiviral Research. 2002 September; 55(3): 447-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206882&dopt=Abstract
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Anti-herpes simplex virus type-1 flavonoids and a new flavanone from the root of Limonium sinense. Author(s): Lin LC, Kuo YC, Chou CJ. Source: Planta Medica. 2000 May; 66(4): 333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865449&dopt=Abstract
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Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes simplex virus in cell culture. Author(s): Schnitzler P, Schon K, Reichling J.
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Source: Pharmazie. 2001 April; 56(4): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338678&dopt=Abstract •
Antiviral activity of characterized extracts from echinacea spp. (Heliantheae: Asteraceae) against herpes simplex virus (HSV-I). Author(s): Binns SE, Hudson J, Merali S, Arnason JT. Source: Planta Medica. 2002 September; 68(9): 780-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357386&dopt=Abstract
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Combined herbal preparation for topical treatment of Herpes labialis. Author(s): Saller R, Buechi S, Meyrat R, Schmidhauser C. Source: Forschende Komplementarmedizin Und Klassische Naturheilkunde = Research in Complementary and Natural Classical Medicine. 2001 December; 8(6): 373-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799306&dopt=Abstract
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Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated from Euphorbia species. Author(s): Mucsi I, Molnar J, Hohmann J, Redei D. Source: Planta Medica. 2001 October; 67(7): 672-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11582549&dopt=Abstract
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Does the extract of the plant Echinacea purpurea influence the clinical course of recurrent genital herpes? Author(s): Vonau B, Chard S, Mandalia S, Wilkinson D, Barton SE. Source: International Journal of Std & Aids. 2001 March; 12(3): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231867&dopt=Abstract
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Evaluation of 2LHERP in preventing recurrences of genital herpes. Institut International 3IDI. Author(s): Jenaer M, Henry MF, Garcia A, Marichal B. Source: Br Homeopath J. 2000 October; 89(4): 174-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055774&dopt=Abstract
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Experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus. Author(s): Dhaliwal DK, Romanowski EG, Yates KA, Hu D, Goldstein M, Gordon YJ. Source: American Journal of Ophthalmology. 2001 April; 131(4): 506-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292417&dopt=Abstract
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Fatal herpes simplex virus hepatitis complicating chemotherapy with weekly docetaxel. Author(s): Hofer S, Hunziker S, Tornillo L, Ludwig CU.
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Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562665&dopt=Abstract •
Genital herpes simplex virus infection in the adolescent: special considerations for management. Author(s): Stanberry LR, Rosenthal SL. Source: Paediatric Drugs. 2002; 4(5): 291-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994034&dopt=Abstract
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Glycyrrhizin increases survival of mice with herpes simplex encephalitis. Author(s): Sekizawa T, Yanagi K, Itoyama Y. Source: Acta Virol. 2001 February; 45(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394578&dopt=Abstract
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Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis. Author(s): Thompson KA, Blessing WW, Wesselingh SL. Source: Journal of Neurovirology. 2000 February; 6(1): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10786994&dopt=Abstract
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Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. Author(s): Yaghoubi S, Barrio JR, Dahlbom M, Iyer M, Namavari M, Satyamurthy N, Goldman R, Herschman HR, Phelps ME, Gambhir SS. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 August; 42(8): 1225-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483684&dopt=Abstract
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Improved herpes simplex virus type 1 amplicon vectors for proportional coexpression of positron emission tomography marker and therapeutic genes. Author(s): Jacobs AH, Winkeler A, Hartung M, Slack M, Dittmar C, Kummer C, Knoess C, Galldiks N, Vollmar S, Wienhard K, Heiss WD. Source: Human Gene Therapy. 2003 February 10; 14(3): 277-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639307&dopt=Abstract
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Improving the outcome of facial resurfacing--prevention of herpes simplex virus type 1 reactivation. Author(s): Gilbert S. Source: The Journal of Antimicrobial Chemotherapy. 2001 February; 47 Suppl T1: 29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160033&dopt=Abstract
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In vitro antiviral activity of Phyllanthus orbicularis extracts against herpes simplex virus type 1. Author(s): Fernandez Romero JA, Del Barrio Alonso G, Romeu Alvarez B, Gutierrez Y, Valdes VS, Parra F. Source: Phytotherapy Research : Ptr. 2003 September; 17(8): 980-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13680841&dopt=Abstract
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In vitro antiviral effect of flavonoid-rich extracts of Vitex polygama (Verbenaceae) against acyclovir-resistant herpes simplex virus type 1. Author(s): Goncalves JL, Leitao SG, Monache FD, Miranda MM, Santos MG, Romanos MT, Wigg MD. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 November; 8(6): 477-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824525&dopt=Abstract
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In vivo antiviral activity of Stephania cepharantha against herpes simplex virus type1. Author(s): Nawawi A, Nakamura N, Meselhy MR, Hattori M, Kurokawa M, Shiraki K, Kashiwaba N, Ono M. Source: Phytotherapy Research : Ptr. 2001 September; 15(6): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11536378&dopt=Abstract
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Inhibitory effect of anti-pyretic and anti-inflammatory herbs on herpes simplex virus replication. Author(s): Hsiang CY, Hsieh CL, Wu SL, Lai IL, Ho TY. Source: The American Journal of Chinese Medicine. 2001; 29(3-4): 459-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789588&dopt=Abstract
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Inhibitory effect of sulfated galactans from the marine alga Bostrychia montagnei on herpes simplex virus replication in vitro. Author(s): Duarte ME, Noseda DG, Noseda MD, Tulio S, Pujol CA, Damonte EB. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 January; 8(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292240&dopt=Abstract
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LongoVital and herpes labialis: a randomised, double-blind, placebo-controlled study. Author(s): Pedersen A. Source: Oral Diseases. 2001 July; 7(4): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575872&dopt=Abstract
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Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein. Author(s): Kotsakis A, Pomeranz LE, Blouin A, Blaho JA.
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Source: Journal of Virology. 2001 September; 75(18): 8697-711. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507215&dopt=Abstract •
Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2. Author(s): Lavelle EC, Grant G, Pusztai A, Pfuller U, Leavy O, McNeela E, Mills KH, O'Hagan DT. Source: Immunology. 2002 October; 107(2): 268-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383207&dopt=Abstract
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Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter gene. Author(s): Liang Q, Nguyen K, Satyamurthy N, Barrio JR, Phelps ME, Gambhir SS, Herschman HR. Source: Gene Therapy. 2002 December; 9(24): 1659-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457279&dopt=Abstract
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Novel mechanism of antibody-independent complement neutralization of herpes simplex virus type 1. Author(s): Friedman HM, Wang L, Pangburn MK, Lambris JD, Lubinski J. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 October 15; 165(8): 4528-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11035093&dopt=Abstract
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NP-1, a rabbit alpha-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2. Author(s): Sinha S, Cheshenko N, Lehrer RI, Herold BC. Source: Antimicrobial Agents and Chemotherapy. 2003 February; 47(2): 494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543649&dopt=Abstract
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Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1. Author(s): Farassati F, Yang AD, Lee PW. Source: Nature Cell Biology. 2001 August; 3(8): 745-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483960&dopt=Abstract
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Oncolytic herpes simplex virus-1 lacking ICP34.5 induces p53-independent death and is efficacious against chemotherapy-resistant ovarian cancer. Author(s): Coukos G, Makrigiannakis A, Kang EH, Rubin SC, Albelda SM, MolnarKimber KL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 August; 6(8): 3342-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955822&dopt=Abstract
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Oncolytic viral therapy for human ovarian cancer using a novel replication-competent herpes simplex virus type I mutant in a mouse model. Author(s): Nawa A, Nozawa N, Goshima F, Nagasaka T, Kikkawa F, Niwa Y, Nakanishi T, Kuzuya K, Nishiyama Y. Source: Gynecologic Oncology. 2003 October; 91(1): 81-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529666&dopt=Abstract
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Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variants. Author(s): Pantuck AJ, Matherly J, Zisman A, Nguyen D, Berger F, Gambhir SS, Black ME, Belldegrun A, Wu L. Source: Human Gene Therapy. 2002 May 1; 13(7): 777-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975845&dopt=Abstract
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Patient and physician partnerships in managing genital herpes. Author(s): Alexander L, Naisbett B. Source: The Journal of Infectious Diseases. 2002 October 15; 186 Suppl 1: S57-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353188&dopt=Abstract
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Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo. Author(s): Jacobs A, Tjuvajev JG, Dubrovin M, Akhurst T, Balatoni J, Beattie B, Joshi R, Finn R, Larson SM, Herrlinger U, Pechan PA, Chiocca EA, Breakefield XO, Blasberg RG. Source: Cancer Research. 2001 April 1; 61(7): 2983-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306477&dopt=Abstract
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Possible mode of antiviral activity of acidic protein bound polysaccharide isolated from Ganoderma lucidum on herpes simplex viruses. Author(s): Eo SK, Kim YS, Lee CK, Han SS. Source: Journal of Ethnopharmacology. 2000 October; 72(3): 475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10996289&dopt=Abstract
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Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma. Author(s): Cinatl J Jr, Cinatl J, Michaelis M, Kabickova H, Kotchetkov R, Vogel JU, Doerr HW, Klingebiel T, Driever PH. Source: Cancer Research. 2003 April 1; 63(7): 1508-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670897&dopt=Abstract
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Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men. Author(s): Cruess S, Antoni M, Cruess D, Fletcher MA, Ironson G, Kumar M, Lutgendorf S, Hayes A, Klimas N, Schneiderman N.
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Source: Psychosomatic Medicine. 2000 November-December; 62(6): 828-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139003&dopt=Abstract •
Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. Author(s): Inman M, Perng GC, Henderson G, Ghiasi H, Nesburn AB, Wechsler SL, Jones C. Source: Journal of Virology. 2001 April; 75(8): 3636-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264353&dopt=Abstract
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Regions of the herpes simplex virus type 1 latency-associated transcript that protect cells from apoptosis in vitro and protect neuronal cells in vivo. Author(s): Ahmed M, Lock M, Miller CG, Fraser NW. Source: Journal of Virology. 2002 January; 76(2): 717-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752162&dopt=Abstract
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Regulation of herpes simplex virus type 1 replication in Vero cells by Psychotria serpens: relationship to gene expression, DNA replication, and protein synthesis. Author(s): Kuo YC, Chen CC, Tsai WJ, Ho YH. Source: Antiviral Research. 2001 August; 51(2): 95-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431035&dopt=Abstract
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Samarangenin B from Limonium sinense suppresses herpes simplex virus type 1 replication in Vero cells by regulation of viral macromolecular synthesis. Author(s): Kuo YC, Lin LC, Tsai WJ, Chou CJ, Kung SH, Ho YH. Source: Antimicrobial Agents and Chemotherapy. 2002 September; 46(9): 2854-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183238&dopt=Abstract
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Two-drug combinations that increase apoptosis and modulate bak and bcl-X(L) expression in human colon tumor cell lines transduced with herpes simplex virus thymidine kinase. Author(s): McMasters RA, Wilbert TN, Jones KE, Pitlyk K, Saylors RL, Moyer MP, Chambers TC, Drake RR. Source: Cancer Gene Therapy. 2000 April; 7(4): 563-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811474&dopt=Abstract
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Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Author(s): Schuhmacher A, Reichling J, Schnitzler P. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10(6-7): 504-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678235&dopt=Abstract
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Will taking the amino acid supplement lysine prevent or treat the herpes simplex virus? Author(s): Marcason W. Source: Journal of the American Dietetic Association. 2003 March; 103(3): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616258&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to herpes simplex; 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 Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Cold Sores Source: Healthnotes, Inc.; www.healthnotes.com
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Cold Sores Source: Integrative Medicine Communications; www.drkoop.com Genital Herpes Source: Healthnotes, Inc.; www.healthnotes.com Herpes Alternative names: Genital Herpes, Cold Sores Source: Prima Communications, Inc.www.personalhealthzone.com Herpes Simplex Virus Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Sexually Transmitted Diseases Source: Integrative Medicine Communications; www.drkoop.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc.; www.healthnotes.com STDs Source: Integrative Medicine Communications; www.drkoop.com •
Homeopathy Dulcamara Source: Healthnotes, Inc.; www.healthnotes.com Graphites Source: Healthnotes, Inc.; www.healthnotes.com Hepar Sulphuris Calcareum Source: Healthnotes, Inc.; www.healthnotes.com Mercurius Solubilis Source: Healthnotes, Inc.; www.healthnotes.com Natrum Muriaticum Source: Healthnotes, Inc.; www.healthnotes.com Rhus Toxicodendron Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Acyclovir Oral Source: Healthnotes, Inc.; www.healthnotes.com Acyclovir Topical Source: Healthnotes, Inc.; www.healthnotes.com Adenosine Monophosphate Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com Amino Acid K Source: Integrative Medicine Communications; www.drkoop.com Amino Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10003,00.html Antiviral Drugs Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10005,00.html Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Blue-Green Algae Source: Healthnotes, Inc.; www.healthnotes.com Blue-Green Algae Source: Integrative Medicine Communications; www.drkoop.com
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Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com Elderberry Alternative names: Sambucus nigra Source: Healthnotes, Inc.; www.healthnotes.com Eucalyptus Alternative names: Eucalyptus globulus Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Goldenseal Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,791,00.html Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc.; www.healthnotes.com Lemon Balm Alternative names: Melissa officinalis, Melissa Source: Integrative Medicine Communications; www.drkoop.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Liquorice Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
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L-lysine Source: Integrative Medicine Communications; www.drkoop.com Lysine Source: Healthnotes, Inc.; www.healthnotes.com Lysine Alternative names: Amino Acid K, L-Lysine Source: Integrative Medicine Communications; www.drkoop.com Lysine Source: Prima Communications, Inc.www.personalhealthzone.com Lysine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,862,00.html Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Melissa Source: Integrative Medicine Communications; www.drkoop.com Melissa Source: Prima Communications, Inc.www.personalhealthzone.com Melissa Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10043,00.html Melissa Officinalis Source: Integrative Medicine Communications; www.drkoop.com Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Potentilla Alternative names: Cinquefoil, Silverweed; Potentilla sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Prunella Alternative names: Self Heal; Prunella vulgaris L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com
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Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Spirulina Alternative names: Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Thuja Occid Alternative names: Arbor Vitae; Thuja occidentalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com Valacyclovir Source: Healthnotes, Inc.; www.healthnotes.com Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON HERPES SIMPLEX Overview In this chapter, we will give you a bibliography on recent dissertations relating to herpes simplex. 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 “herpes simplex” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on herpes simplex, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Herpes Simplex 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 herpes simplex. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Role for Nuclear Factor-kappab in Apoptosis Modulation during Herpes Simplex Virus Type 1 Infection by Goodkin, Margot L.; PhD from Mount Sinai School of Medicine of New York University, 2002, 208 pages http://wwwlib.umi.com/dissertations/fullcit/3058862
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Analysis of the Genes Encoding the Latency Associated Transcript of Bovine Herpesvirus Type 1 (bhv-1) and Herpes Simplex Type 1: Their Anti-apoptotic Activity and a Novel Function Identified for the Bhv-1 Latency Related Gene by Inman, Melissa Anne; PhD from University of Nebraska Medical Center, 2002, 234 pages http://wwwlib.umi.com/dissertations/fullcit/3068773
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Anti-apoptotic Activity of the Herpes Simplex Virus Type 2 Gene Icp10 Pk: Implications for Therapy of Neurological Disorders That Involve Apoptosis by Perkins, Dana Stela; PhD from University of Maryland, Baltimore, 2002, 321 pages http://wwwlib.umi.com/dissertations/fullcit/3048445
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Antigens of Herpes Simplex Virus by Rigby, Charlotte; PhD from University of Ottawa (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK10694
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Antiviral Activities of Selected Hong Kong Marine Algae against Herpes Simplex Viruses and Other Viruses and Their Possible Antiviral Mechanisms by Zhu, Wen; PhD from Chinese University of Hong Kong (People's Republic of China), 2002, 249 pages http://wwwlib.umi.com/dissertations/fullcit/3052129
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Biochemical and Genetic Characterization of Temperature-sensitive Mutants of Herpes Simplex Virus Type 1 Defective in the Shutoff of Cellular Macromolecular Synthesis by Daksis, Jasmine Ilga; PhD from University of Toronto (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39717
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Characterization of Presynaptic C-afferent Fiber Responses: a Recombinant Herpes Simplex Virus-1 Approach by Jones, Toni L.; PhD from University of Illinois at Chicago, Health Sciences Center, 2003, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3083945
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Characterization of the Herpes Simplex Virus Ribonucleotide Reductase by Huszar, Dennis; PhD from McMaster University (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NL17587
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Dissecting the Functions of Neurovirulent Factor Icp34.5 Protein of Herpes Simplex Virus 1 by Cheng, Guofeng; PhD from University of Illinois at Chicago, Health Sciences Center, 2003, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3083941
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Factors Affecting the Prevalence of Herpes Simplex Virus Type 2 Antibody a Seroepidemiologic Survey by Chiavetta, Jo Anne; PhD from The University of Western Ontario (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33044
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Functional Analysis of Ul9, the Origin-binding Protein of Herpes Simplex Virus-1 by Marintcheva, Boriana Davidova; PhD from the University of Connecticut, 2002, 239 pages http://wwwlib.umi.com/dissertations/fullcit/3076711
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Herpes Simplex Virus Type 1 (hsv-1) U(l)31, U(l)33, and U(l)34 Proteins Play Essential Roles in Herpesvirion Morphogenesis by Reynolds, Ashley Elizabeth; PhD from Cornell University, 2002, 195 pages http://wwwlib.umi.com/dissertations/fullcit/3059106
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Herpes Simplex Virus Type-1 Icp34.5 Modulates Neuroinvasiveness in Vivo, Viral Plaque Size, Efficiency of Glycoprotein Processing, and Viral Release in Tissue Culture by Mao, Hanwen; PhD from Kent State University, 2002, 239 pages http://wwwlib.umi.com/dissertations/fullcit/3068690
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Herpes Simplex Virus-based Vectors in Neurons and Glia: Transgene Expression and Immune Response by Harvey, Brandon Keith; PhD from The University of Rochester, 2003, 247 pages http://wwwlib.umi.com/dissertations/fullcit/3078411
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Hijacking of the Ubiquitin-proteasome System by Herpes Simplex Virus 1: Description and Characterization of Two Discrete E3 Ubiquitin Ligase Activities Encoded by Infected Cell Protein 0 by Hagglund, Ryan; PhD from The University of Chicago, 2003, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3088740
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Identification and Characterization of Protein Interaction Domains in the Herpes Simplex Virus Type I Transcription Factor Icp4 by Bruce, James William; PhD from The Medical College of Wisconsin, 2002, 241 pages http://wwwlib.umi.com/dissertations/fullcit/3041767
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Inhibition of the Herpes Simplex Virus Type I by Three Ndga Derivatives: Mal.4, M(4)n, and G(4)n by Park, Richard; PhD from The Johns Hopkins University, 2003, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3068194
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Intranuclear Localization of the Herpes Simplex Virus Icp8 Protein by Taylor, Travis J.; PhD from Harvard University, 2002, 253 pages http://wwwlib.umi.com/dissertations/fullcit/3051302
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Mechanism of Herpes Simplex Virus Type 1 Latency in Transgenic Mouse Models by Loiacono, Christina Marie; PhD from University of Missouri - Columbia, 2002, 104 pages http://wwwlib.umi.com/dissertations/fullcit/3052194
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Mechanisms of Herpes Simplex Virus Retinitis in a Mouse Model by Archin, Nancie Marie; PhD from The University of Texas Health Science Center at San Antonio, 2002, 186 pages http://wwwlib.umi.com/dissertations/fullcit/3070649
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Molecular Characterization of Glycoproteins of Herpes Simplex Virus by Zwaagstra, John Clarence; PhD from University of Alberta (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL41173
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Molecular Mechanism of Recombination in Herpes Simplex Virus Type-1 by Nimonkar, Amitabh Vijay; PhD from University of Miami, 2003, 136 pages http://wwwlib.umi.com/dissertations/fullcit/3096356
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Processivity of the Herpes Simplex Virus Dna Polymerase: Role of High-affinity Dna Binding by the Processivity Subunit by Randell, John Cranston Wall; PhD from Harvard University, 2003, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3076910
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Quantitating Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression in Living Animals Using Positron Emission Tomography and a Tracer Kinetic Model for Radiolabeled Acyclic Guanosine Analogues by Green, Leeta Alison; PhD from University of California, Los Angeles, 2003, 218 pages http://wwwlib.umi.com/dissertations/fullcit/3094197
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Radiohalogenated Pyrimidine Nucleosides As Potential Non-invasive Diagnostic Agents for Herpes Simplex Encephalitis by Samuel, John; PhD from University of Alberta (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL22934
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Recombinational and Packaging Signals in Herpes Simplex Virus Deoxyribonucleic Acid by Varmuza, Susannah Louise; PhD from Mcmaster University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24111
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Signaling Mechanisms Essential for Reactivation of Latent Herpes Simplex Virus Type 1 in Neuronal Cultures by Hunsperger, Elizabeth Anne; PhD from Colorado State University, 2002, 112 pages http://wwwlib.umi.com/dissertations/fullcit/3053429
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Stress and Stress-associated Neuroendocrine Hormones Modulate the Function of Herpes Simplex Virus-specific Memory Cytotoxic T Lymphocytes by Wonnacott, Keith Merrell; PhD from The Pennsylvania State University, 2002, 233 pages http://wwwlib.umi.com/dissertations/fullcit/3051762
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Stress-induced Reactivation of Latent Herpes Simplex Virus Infection in Lumbar Ganglia of Rats by Blondeau, Joseph Moses; PhD from The University of Manitoba (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL51624
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Structural Determinants of Nectin-1 and Nectin-2 Required for Entry of Herpes Simplex Virus and Other Alphaherpesviruses by Martinez, Wanda M.; PhD from Northwestern University, 2002, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3050560
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Structure-based Analysis of Herpes Simplex Virus Glycoprotein D and Its Hvea/hvem Receptor by Connolly, Sarah Ann; PhD from University of Pennsylvania, 2003, 188 pages http://wwwlib.umi.com/dissertations/fullcit/3087386
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Studies on Latent Herpes Simplex Virus in the Human Nervous System by Lewis, Marcia Ellen; PhD from University of Alberta (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK67540
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Studies on the Anti-herpes Simplex Virus (hsv) Constituents from a Chinese Herbal Medicine, Prunella Vulgaris by Zhang, Yongwen; PhD from Chinese University of Hong Kong (People's Republic of China), 2003, 190 pages http://wwwlib.umi.com/dissertations/fullcit/3095430
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Study about the Mechanism of Liver Toxicity Induced by the Treatment with Herpes Simplex Virus Thymidine Kinase Plus Ganciclovir by Herraiz Bayod, Maite; DR from Universidad De Navarra (Spain), 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/f403153
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The Association of Herpes Simplex Virus with Cervical Cancer a Mathematical Model, and Exploration of an Approach to Retrieve Viral Genetic Information from Transformed Cells by Campione-Piccardo, Jose; PhD from McMaster University (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK54139
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The Mechanisms of Ablation of Antiviral Effects of Interferon by Herpes Simplex Virus Type 1 by Chee, Ana Virginia; PhD from The University of Chicago, 2003, 131 pages http://wwwlib.umi.com/dissertations/fullcit/3077047
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The Role of Herpes Simplex Virus Type 2 (hsv-2) As a Cofactor in HIV Transmission by Mbopi-Keou, Francois-Xavier; PhD from Open University (United Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f803585
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The Role of Perforin and Chemokines in the Pathogenesis of Chronic Corneal Inflammation Induced by Herpes Simplex Virus Type-1 Infection by Chang, Eddie; PhD from University of Missouri - Columbia, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3091911
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Transcriptional Analysis of Herpes Simplex Virus Type 1 Expression and Host Cell Response to Infection Using a Dna Microarray by Stingley, Samuel Wayne; PhD from University of California, Irvine, 2002, 258 pages http://wwwlib.umi.com/dissertations/fullcit/3039229
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Use of Expresser Cell Lines to Functionally Characterize the Herpes Simplex Virus Transcription-activating Protein by Persson, Roy H; PhD from McMaster University (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL52142
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Vp16 Localization during Herpes Simplex-1 Infection by Greensides, Dawn Renee; MS from Michigan State University, 2002, 209 pages http://wwwlib.umi.com/dissertations/fullcit/1409511
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 HERPES SIMPLEX Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning herpes simplex.
Recent Trials on Herpes Simplex The following is a list of recent trials dedicated to herpes simplex.8 Further information on a trial is available at the Web site indicated. •
Assessment of oral acyclovir in neonates with HSV involving the CNS Condition(s): Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to test whether long-term treatment (6 months) with oral acyclovir improves the outcome for infants with HSV infection of the brain or spinal cord (central nervous system, or CNS disease). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031460
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HERPEVAC Trial for Women Condition(s): Herpes Simplex; Sexually Transmitted Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The primary purpose of this study is to see if the vaccine is safe and prevents genital herpes disease in women who are not infected.
8
These are listed at www.ClinicalTrials.gov.
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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057330 •
Oral acyclovir for neonatal HSV disease of the skin,eyes and mouth Condition(s): Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to test whether long-term treatment with oral acyclovir improves the outcome for infants with HSV disease of the skin, eyes, and mouth (SEM disease). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031447
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Phase III Randomized Study of Oral Acyclovir in Infants With Herpes Simplex Virus Infection Involving the Central Nervous System Condition(s): Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the efficacy of long term suppressive therapy with oral acyclovir in infants with herpes simplex virus infection involving the central nervous system. II. Determine whether neurologic outcome is improved in these patients when treated with this regimen. III. Determine whether continuous administration of this drug suppresses recurrent skin lesions in these patients. IV. Determine the safety of this regimen in these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006132
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Phase III Randomized Study of Oral Acyclovir in Infants With Herpes Simplex Virus Infection Limited to Skin, Eyes, and Mouth Condition(s): Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the efficacy of long term suppressive therapy with oral acyclovir in infants with herpes simplex virus infection limited to skin, eyes, and mouth. II. Determine the neurologic outcome in these patients when treated with
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this regimen. III. Evaluate the significance of a positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) result when all other CSF parameters remain normal in these patients. IV. Correlate the time to first positive CSF PCR result in the first 12 months of life with clinical neurological assessment in these patients when treated with this regimen. V. Determine whether the continuous administration of this drug suppresses recurrent skin lesions in these patients. VI. Determine the safety of this regimen in these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006135 •
Structure of the Herpes Simplex Virus Receptor Condition(s): Encephalitis; Herpes Simplex; Keratitis; Mouth Disease; Skin Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the structure of the receptor molecule for the herpes simplex virus (HSV) and determine if the receptor's structure is related to susceptibility to infection with the virus. There are two types of herpes virus-HSV-1 and HSV-2. HSV-1 commonly causes cold sores, and HSV-2 usually causes genital herpes. The herpes virus enters (infects) cells through protein molecules on the cell's surface. This study will explore possible differences between the structure of the HSV receptor molecule in different people to understand better how infection occurs. The study will also look at proteins on white blood cells (Fc receptors, cytokines and mannose binding protein) that may influence the risk of infection with HSV. Information from this study may lead to new treatments to prevent HSV infection. People 18 years of age and older who are infected with HSV and people who are not infected with the virus may be eligible for this study. Participants will have blood drawn to confirm whether or not they have been infected with the virus. The blood sample will also be used to study the genes for the HSV receptor, Fc receptors, cytokines, mannose binding protein and related proteins on the white blood cells. No more than 40 milliliters (8 teaspoons) of blood will be drawn. Participants who are found to have antibodies to HSV-2 will be offered counseling and advice on practicing safe sex techniques to help prevent sexually transmitted diseases, including HSV-2 infection. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001648
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Valacyclovir for longterm therapy of Herpes simplex encephalitis Condition(s): Encephalitis, Herpes Simplex Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if giving Valacyclovir (VACV) to patients with herpes simplex encephalitis (HSE) can increase the survival rates of these patients and reduce brain and nervous system damage. A sub-study will also be
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performed to look at the relationship between the level of herpes virus in the blood and "long-term" brain damage injury caused by the HSE infection. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031486 •
A Study of Valacyclovir as Treatment for Genital Herpes Simplex Virus in HIVInfected Patients Condition(s): Herpes Simplex; HIV Infections; Herpes Genitalis Study Status: This study is no longer recruiting patients. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: The purpose of this study is to see if valacyclovir (Valtrex) is a safe and effective treatment for ano-genital HSV infections (herpes simplex virus infections of the anus and external genitals) in HIV-infected patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005663
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Herpetic Eye Disease Study (HEDS) II Condition(s): Keratitis, Herpetic; Ocular Herpes Simplex; Herpes Simplex Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether early treatment (with oral acyclovir) of herpes simplex virus (HSV) ulcerations of the corneal epithelium prevents progression to the blinding complications of stromal keratitis and iridocyclitis. To determine the efficacy of low-dose oral acyclovir in preventing recurrent HSV eye infection in patients with previous episodes of herpetic eye disease. To determine the role of external factors (such as ultraviolet light or corneal trauma) and behavioral factors (such as life stress) on the induction of ocular recurrences of HSV eye infections and disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000139
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HIV and Genital Herpes Among High-Risk Men Who Have Sex With Men (MSM) in Lima, Peru Condition(s): HIV Infections; Herpes Genitalis; HIV Seronegativity; Syphilis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)
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Purpose - Excerpt: The purpose of this study is to provide biomedical and behavioral information that is necessary for planning and starting HIV prevention trials in Lima, Peru. The occurrence of HIV is high among men who have sex with men (MSM) in Lima, Peru, and bacterial sexually transmitted diseases (STDs) and HSV-2 (genital herpes) are very prevalent in HIV-positive and -negative MSM there. Methods to reduce both HIV and STDs are urgently needed among MSM in Peru. The information gained from this study is very important for future HIV prevention and vaccine trials that will take place in Peru. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023582 •
A Comparative Trial of Valacyclovir Hydrochloride ( 256U87 ) and Acyclovir for the Suppression of Anogenital Herpes Infections in HIV-Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: To determine the safety and efficacy of oral valacyclovir hydrochloride ( 256U87 ) compared to acyclovir in the treatment of recurrent anogenital herpes in HIV-infected patients with CD4 counts = or > 100 cells/mm3. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002084
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A Phase I/II Study of the Safety and Efficacy of Topical 1-(S)-(3-Hydroxy-2phosphonylmethoxypropyl)cytosine Dihydrate (Cidofovir; HPMPC) in the Treatment of Refractory Mucocutaneous Herpes Simplex Disease in Patients With AIDS Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Gilead Sciences Purpose - Excerpt: To evaluate the safety and tolerance of topical cidofovir (HPMPC) therapy for refractory mucocutaneous herpes simplex virus disease in AIDS patients. To determine whether topical HPMPC therapy can induce re-epithelialization and healing of refractory mucocutaneous herpes simplex virus disease in AIDS patients. To evaluate the virologic effects of topical HPMPC therapy on herpes simplex virus shedding from refractory lesions. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002116
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A Study to Compare the Efficacy and Safety of Valacyclovir Hydrochloride ( 256U87 ) Versus Acyclovir in the Treatment of Recurrent Anogenital Herpes Infections in HIV Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: To evaluate the safety and efficacy of oral valacyclovir hydrochloride (256U87) vs. acyclovir in the treatment of recurrent anogenital herpes in HIV-infected patients (CD4 greater than or equal to 100). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002000
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An Open Study of Foscarnet Treatment of Acyclovir-Resistant Herpes Simplex Virus in Patients With the Acquired Immunodeficiency Syndrome and Other Immunodeficiencies Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Astra USA Purpose - Excerpt: To evaluate the safety and efficacy of intermittent intravenous (IV) foscarnet in the treatment of acyclovir-resistant herpes simplex virus (HSV) infections in AIDS patients and other immunocompromised patients. To evaluate the necessity, efficacy, and safety of IV maintenance foscarnet therapy in preventing recurrent disease. To confirm the pharmacokinetics of intermittent induction and maintenance IV regimens. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002021
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An Open, Multicenter Study of Foscarnet Treatment of Acyclovir-Resistant Herpes Simplex Virus in Patients With the Acquired Immunodeficiency Syndrome and Other Immunodeficiencies Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Astra USA Purpose - Excerpt: To evaluate the safety and efficacy of intermittent intravenous (IV) foscarnet in the treatment of acyclovir-resistant herpes simplex virus (HSV) infections in AIDS patients and other immunocompromised patients. To evaluate the necessity, efficacy, and safety of IV maintenance foscarnet therapy in preventing recurrent disease. To confirm the pharmacokinetics of intermittent induction and maintenance IV regimens. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002272
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Cidofovir as a Treatment for Herpes Simplex in Patients with AIDS Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Gilead Sciences Purpose - Excerpt: The purpose of this study is to see if cidofovir gel (Forvade) is safe and effective in treating herpes simplex in patients with AIDS who do not respond to acyclovir. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002181
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Comparison of Foscarnet Versus Vidarabine in the Treatment of Herpes Infection in Patients with AIDS Who Have Not Had Success with Acyclovir Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: To compare the safety and effectiveness of foscarnet and vidarabine treatments for AIDS patients who have herpes simplex virus infections that are resistant to standard treatment with acyclovir. Foscarnet is a drug that inhibits viruses and has been shown to be effective against infection with Cytomegalovirus and also against infection with the Herpes simplex virus in several patients with AIDS. Vidarabine has been shown to have activity against the Herpes simplex virus in patients who do not have AIDS, but it has not been studied in patients who do have AIDS. This study compares foscarnet and vidarabine treatments for AIDS patients who have herpes simplex infection that has not responded to therapy with acyclovir in the hope that one of these two drugs will help to stop further progression of the herpes simplex infection and may have fewer side effects. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000985
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Double-Blind Placebo-Controlled Study Comparing the Combination of 15% SP-303 Gel with Acyclovir Versus Acyclovir Alone for the Treatment of Recurrent Herpes Simplex Virus (HSV) Infections in Subjects with Acquired Immunodeficiency Syndrome (AIDS) Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Shaman Pharmaceuticals Purpose - Excerpt: To evaluate the safety of topically applied SP-303 gel and to compare the efficacy of SP-303 gel in combination with acyclovir, relative to acyclovir alone, for the treatment of recurrent Herpes Simplex Virus (HSV) 1 and 2 infections, affecting the genital, perianal and neighboring areas, in patients with AIDS. Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002186 •
Herpetic Eye Disease Study (HEDS) I Condition(s): Keratitis, Herpetic; Ocular Herpes Simplex Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis in conjunction with topical trifluridine. To evaluate the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine. To evaluate the efficacy of oral acyclovir in treating herpes simplex iridocyclitis in conjunction with treatment with topical corticosteroids and trifluridine. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000138
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Phase I/II Study of High-Dose Acyclovir for Central Nervous System or Disseminated Neonatal Herpes Simplex Virus Infection Condition(s): Herpes Simplex Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Objectives: I. Evaluate whether high-dose acyclovir decreases acute and long-term morbidity and mortality in neonates with central nervous system or disseminated herpes simplex virus (HSV) infection. II. Evaluate whether high-dose acyclovir is safe and tolerated in the newborn. III. Assess resistance to antiviral medication. IV. Amplify disease classification for the purpose of predicting prognosis. V. Assess any changes in viral excretion patterns. VI. Evaluate whether antigens and antibodies specific for HSV glycoproteins within the cerebrospinal fluid (CSF) predict long-term neurologic outcome. VII. Evaluate whether specific antigens and antibodies in the CSF appear late after treatment and are indicative of insidious reactivation of virus in the brain. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004644
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Phase III Randomized, Placebo-Controlled Study of Acyclovir Oral Suspension for Neonatal Herpes Simplex Virus Infection Limited to the Skin, Eyes, and Mouth Condition(s): Herpes Simplex Study Status: This study is completed.
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Sponsor(s): National Center for Research Resources (NCRR); National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Objectives: I. Determine whether acyclovir (ACV) oral suspension suppresses recurrent skin lesions and improves neurologic outcome in neonates with localized herpes simplex virus type 2 infection when administered for 6 months in a placebo-controlled study. II. Determine whether the prevention of recurrent skin lesions reduces long-term neurologic morbidity. III. Determine whether resistant disease develops after oral ACV therapy. IV. Evaluate the natural history of recurrent skin lesions. V. Measure any adverse effects and laboratory abnormalities associated with long-term oral ACV therapy in infants and young children. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004757 •
SP-303T Applied to the Skin of Patients with Herpes Simplex Virus (HSV) Infection and AIDS Who Have Not Had Success with Acyclovir Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Shaman Pharmaceuticals Purpose - Excerpt: To evaluate the safety and tolerance of topically applied SP-303T in AIDS patients. To observe the effect of this drug on herpes simplex virus lesions in patients who have failed to heal in response to oral or intravenous acyclovir therapy. The lack of alternative treatments for herpes simplex virus infection in patients with AIDS and the development of resistance to acyclovir for patients requiring repeated treatment presents a therapeutic dilemma for physicians. SP-303T has good in vitro activity against resistant strains and offers a convenient and inexpensive means of drug administration in comparison to the use of intravenous medication. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002310
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The Effect of Acyclovir Treatment of the Herpes Simplex Virus (HSV) Infection on HIV Levels in the Blood Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Part A: To evaluate the impact of HSV suppression with acyclovir ( ACV ) on HIV burden in patients with asymptomatic HSV infection and at high risk for HSV reactivation. Part B: To characterize the change in plasma HIV RNA levels and other measures of HIV burden during and after a 10 day course of ACV treatment for acute HSV infection. Approximately 70% of patients infected with HIV are concurrently infected with HSV. There is new evidence to suggest that HSV may act as a co-factor in HIV disease progression. This study will attempt to determine if the upregulation of HIV RNA that occurs during symptomatic HSV reactivation also occurs during
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asymptomatic HSV reactivation and if suppression of HSV will result in decreased levels of HIV RNA. There is a need to determine the patterns of association between HSV and HIV. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001115 •
The Effect of Valacyclovir on the Detection of HIV from Genital Herpes Lesions in HIV-Infected Patients Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: The purpose of this study is to see if valacyclovir affects the detection of HIV in genital herpes lesions in HIV-infected patients. Valacyclovir is used to treat recurrent genital herpes. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002404
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The Pilot Study of Foscarnet Cream in the Treatment of Mucocutaneous Herpes Simplex Virus Infections in Immunocompromised Patients Unresponsive to Acyclovir Treatment Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): Astra USA Purpose - Excerpt: PRIMARY: To evaluate the clinical activity of foscarnet cream on the index lesion of mucocutaneous herpes simplex virus (HSV) infections in immunocompromised patients previously unresponsive to acyclovir treatment. SECONDARY: To evaluate the clinical activity and virologic activity of foscarnet cream on all treated lesions in this patient population. To evaluate the local tolerance and side effects of treatment with foscarnet cream in this patient population. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002144
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The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children Condition(s): Herpes Simplex; HIV Infections; Chickenpox Study Status: This study is terminated. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Glaxo Wellcome
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Purpose - Excerpt: To obtain tolerance, safety, and pharmacokinetic data for oral valacyclovir hydrochloride ( 256U87 ) in HIV-1 infected children with herpes simplex virus infections ( cold sores ) and/or varicella / zoster virus infections ( chicken pox / shingles ). Varicella and zoster are common problems in HIV-infected children. It is believed that chronic oral therapy with acyclovir may result in subtherapeutic concentrations of acyclovir, resulting in resistance to that drug. Valacyclovir hydrochloride, which converts to acyclovir in the body, increases acyclovir bioavailability by 3-5 fold. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001054 •
The Tolerance of HIV-Infected Patients with Herpes Group Virus Infections to Oral Doses of FIAU Condition(s): Herpes Simplex; HIV Infections; Hepatitis B Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Oclassen Pharmaceuticals Purpose - Excerpt: To determine the tolerance of HIV-infected patients to TID oral doses of FIAU syrup at 4 different dose levels. To determine the peak and trough blood levels of FIAU and its metabolites during two weeks of oral dosing with FIAU. The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000654
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Treating Genital Herpes to Decrease Risk of HIV Transmission Condition(s): HIV Infections; Herpes Genitalis Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test whether treating genital herpes decreases the chances of a person getting HIV. Phase(s): Phase III Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068965 •
Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex Disease in Patients With AIDS: Open Label Pilot Study of Topical Trifluridine Condition(s): Herpes Simplex; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Glaxo Wellcome Purpose - Excerpt: To determine the safety, effectiveness, and toxicity of topical (local) trifluridine in treating mucocutaneous (at the nasal, oral, vaginal, and anal openings) Herpes simplex virus ( HSV ) disease that has shown resistance to acyclovir in HIVinfected patients. HSV infection in patients with AIDS is often associated with skin sores and frequent recurrences. Treatment with the drug acyclovir results in healing for most patients, but repeated treatment sometimes results in resistance of the virus to acyclovir. Thus, when this happens, other treatments need to be used. Trifluridine is an antiviral drug that is used for the treatment of Herpes infections that occur in the eye. This study attempts to determine if trifluridine is useful for treating HSV sores that have not healed after treatment with acyclovir. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000635
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Valaciclovir to Prevent Transmission of Herpes Simplex Virus Condition(s): Herpes Simplex Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the effectiveness of the drug valaciclovir in preventing transmission of genital herpes from an infected to an uninfected sexual partner. Genital herpes is caused by the herpes simplex virus 2 (HSV-2), or, infrequently herpes simplex virus 1 (HSV-1). Valaciclovir prevents the herpes virus from multiplying and may also reduce its transmission between partners. Couples 18 years of age and older in which one partner is infected with HSV-2 (source partner) and the other is not (susceptible partner), may be eligible for this study. Candidates will be screened with blood tests for routine laboratory studies and to verify the presence or absence of HSV-2 or HSV-1 infection. Participants will give a medical history, undergo a physical examination, including genital examination, and receive counseling on safer sex practices and how to recognize signs and symptoms of a possible first episode of genital herpes. Source partners will also be counseled on transmission of genital herpes, and susceptible partners will be interviewed about their sexual history and practices. The source partner will be randomly assigned to take either a 500-mg tablet of valaciclovir or placebo (a pill with no active ingredient) daily for 8 months. All participants will be given diary cards to complete for a month-the source partner will record any drug side effects and the susceptible partner will record any signs or symptoms of possible HSV infection. Participants will be seen in the clinic once a month for 8 months. At these visits, source partners will 1) return unused study medication and the completed diary card; 2) discuss any adverse drug side effects experienced in the last month; 3) review
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medications other than the study drug taken in the last month; 4) undergo counseling on safer sex practices, transmission of genital herpes, and recognizing signs and symptoms of a first episode of genital herpes; and 5) review symptoms and recurrences of genital herpes experienced during the last month. During the final visit, they will also provide a blood sample for routine testing and possible use in future studies. Susceptible partners will 1) have a blood sample drawn for HSV testing; 2) undergo safer sex counseling; 3) review any symptoms experienced over the last month; 4) be interviewed about sexual exposure and practices; and 5) return the completed diary card. Source partners who have a recurrence of genital HSV while on the study will be asked to have their lesions cultured and will be offered open-label valaciclovir treatment. Susceptible partners who contract genital herpes from the source partner during the study will have a genital examination to verify a fist episode of genital herpes and will receive 10 days of open-label treatment with valaciclovir. Cultures will be taken from the mouth and genitals, current medical conditions will be reviewed, blood samples will be drawn on treatment days 1 and 10, and treatment side effects will be reviewed on days 5 and 10. At the end of the study, infected partners will be offered a 12-month course of valaciclovir, one 500-mg tablet daily. Participants will be followed in the clinic once every 3 months to provide blood samples, return unused study medication and the diary card, discuss any drug side effects, review medications taken besides the study drug, and review symptoms or recurrences of genital herpes. All participants will be asked to complete a questionnaire for gathering information about people with genital herpes and people at risk for the infection. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001649
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 “herpes simplex” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON HERPES SIMPLEX Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “herpes simplex” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on herpes simplex, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Herpes Simplex By performing a patent search focusing on herpes simplex, 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. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on herpes simplex: •
4-hydroxycinnoline-3-carboxyamides as antiviral agents Inventor(s): Larsen; Scott D. (Kalamazoo, MI), Nair; Sajiv K. (Kalamazoo, MI), Vaillancourt; Valerie A. (Kalamazoo, MI) Assignee(s): Pharmacia & Upjohn Company (Kalamazoo, MI) Patent Number: 6,458,788 Date filed: March 15, 2001 Abstract: Certain novel 4-hydroxycinnoline-3-carboxyamides. The compounds are particularly effective in the treatment or prevention of viral infections, particularly infections caused by herpes viruses including herpes simplex virus types 1 and 2, human herpes virus types 6, 7 and 8, varicello zoster virus, human cytomegalovirus or Epstein-Barr virus. Excerpt(s): The present invention provides novel cinnolines, which are useful as antiviral agents (e.g. as agents against viruses of the herpes family). The herpesviruses comprise a large family of double stranded DNA viruses. They are also a source of the most common viral illnesses in man. Eight of the herpes viruses, herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human cytomegalovirus (HCMV), epstein-Barr virus (EBV), and human herpes viruses 6, 7, and 8 (HHV-6, HHV7, and HHV-8), have been shown to infect humans. U.S. Pat. No. 4,826,837 discloses 4hydroxycinnoline-3-carboxamides and their use for the treatment of neoplastic diseases and acute and chronic infections of both bacterial and viral origin in mammals. Web site: http://www.delphion.com/details?pn=US06458788__
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Anti-apoptotic compositions comprising the R1 subunit of herpes simplex virus ribonucleotide reductase or its N-terminal portion; and uses thereof Inventor(s): Langelier; Yves (Montreal, CA), Massie; Bernard (Montreal, CA) Assignee(s): Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (Montreal, CA) Patent Number: 6,524,821 Date filed: April 6, 2001 Abstract: An anti-apoptotic agent and a composition derived therefrom, and methods to prevent apoptosis in vivo and in vitro are provided. The anti-apoptotic agent comprises R1 subunit of Herpes simplex virus (HSV) ribonucleotide reductase, or its N-terminal portion of about 350 amino acids. HSV-R1 inhibited TNF-.alpha. induced apoptosis, and blocked caspase 8 activation induced by TNF-.alpha. and Fas-L expression. Excerpt(s): This application claims priority to International Application No PCT/CA99/00673, filed Jul. 23, 1999 (Publ. No. WO 00/07618), and Canadian Application No 2,239,248, filed Jul. 31, 1998. The mechanisms for establishment of latent herpes simplex virus infection in neurons and the subsequent reactivation are very poorly understood. Recent studies have shown that the pattern of gene expression during reactivation is not similar to the one seen in the lytic cycle: the expression of early (E) genes, notably the gene for the subunit 1 (R1) of ribonucleotide reductase,
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begins several hours before detectable expression of the immediate early (IE) genes (1-3). HSV can be reactivated by numerous stress conditions including NGF deprivation, hyperthermia and cadmium (4) which are also known to induce neuronal cell apoptosis. Therefore, it might be advantageous for the virus to encode protein(s), which are able to block the apoptotic pathways activated by these stimuli. In addition, such proteins could be important to counteract the action of cytotoxic T lymphocytes (CTL) which prevent virus dissemination in cells of the mucosal epithelia where it replicates after being released from neurons (5). The HSV ribonucleotide reductase converts ribonucleoside diphosphates to the corresponding deoxyribonucleotides and plays a key role in the synthesis of viral DNA (reviewed in (6). The association of two subunits, R1 and R2, the former of which contains the active site, forms the holoenzyme. The R1 subunits of HSV-1 and HSV-2 possess an NH2 domain of about 350 amino acids. This is a unique feature which is not found in R1 of other species, including those of other herpes viruses (7, 8). The role of HSV ribonucleotide reductase has been extensively studied with ribonucleotide reductase null mutants. Studies first done with cultured cells showed that the enzyme is required for efficient replication in non dividing cells. Subsequently, works using animal models demonstrated that the enzyme is required for efficient pathogenicity, is essential for viral reactivation from the neurons, but is not essential for the establishment of latency (9-16). The observations that a mutant virus bearing a deletion of the reductase domain of the R1 gene (hrR3) exhibited the same phenotype in cell culture or in animal models as a virus with a deletion of both the NH2 and the reductase domains (ICP6.DELTA.) has suggested that the NH2 domain may play only a minor role in viral pathogenesis (9, 10, 13). However, as viral mutants which contain deletions only of the R1 NH2 domain have not yet been characterized for their capacity to reactivate, an important role of this domain in HSV reactivation could have been masked by the ribonucleotide reductase deficiency of the two mutants which by itself completely prevents viral replication in the latently infected neurons. Web site: http://www.delphion.com/details?pn=US06524821__ •
Combined hepatitis and herpesvirus antigen compositions Inventor(s): Stephenne; Jean (Rixensart, BE), Wettendorff; Martine Anne Cecile (RhodeSaint-Genese, BE) Assignee(s): SmithKline Beecham Biologicals S.A. (Rixensart, BE) Patent Number: 6,451,320 Date filed: October 27, 2000 Abstract: Novel combined vaccine compositions preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a VZV antigen, an HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3DMPL and QS21. Excerpt(s): This application is a 371 of International Application PCT/EP99/01406, filed Mar. 4, 1999, which claims priority from GB 9805105.5, filed Mar. 9, 1998 and GB 9813561.9, filed Jun. 23, 1998. This invention relates to novel vaccine formulations, methods for preparing them and their use in therapy. In particular the present invention relates to combination vaccines for administration to adolescents. Genital herpes is estimated to occur in about 5 million people in the U.S.A. alone with 500,000 clinical
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cases recorded every year (primary and recurrent infection). Primary infection typically occurs after puberty and is characterised by the localised appearance of painful skin lesions, which persist for a period of between 2 to 3 weeks. Within the following six months after primary infection 50% of patients will experience a recurrence of the disease. About 25% of patients may experience between 10-15 recurrent episodes of the disease each year. In immunocompromised patients the incidence of high frequency recurrence is statistically higher than in the normal patient population. Web site: http://www.delphion.com/details?pn=US06451320__ •
Combined therapy with a chemotherapeutic agent and an oncolytic virus for killing tumor cells in a subject Inventor(s): Kaiser; Larry (Wynnewood, PA), Molnar-Kimber; Katherine (Worcester, PA), Toyoizumi; Takane (Philadelphia, PA) Assignee(s): The Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 6,428,968 Date filed: November 8, 1999 Abstract: The invention includes methods, compositions, and kits for killing tumor cells in a subject such as a human patient. The methods comprise administering both a chemotherapeutic agent and an oncolytic virus other than an adenovirus to a subject which has tumor cells. The agent and virus exhibit oncolytic activities that are at least additive, and that may be synergetic. The oncolytic virus may, for example, be a herpes simplex virus (type 1 or 2), a vaccinia virus, a vesicular stomatitis virus, or a Newcastle disease virus. The compositions and kits comprise a chemotherapeutic agent and an oncolytic virus other than an adenovirus, either in admixture or separately. Excerpt(s): The field of the invention is killing tumor cells in a subject. Cancer remains one of the leading causes of morbidity and mortality of humans worldwide. Known cancer therapies include chemotherapy, radiation, surgery, and gene therapy. The combined use of chemotherapy, radiation, and surgery has augmented the benefits of these therapies in some types of cancer, but in only a few types of cancer has it resulted in eradication of the tumor. Despite the promise afforded by gene therapy anti-cancer strategies, various shortcomings in virus vectors and other gene vectors have limited the efficacy of gene therapy methods for eradicating tumor cells from subjects such as humans afflicted with cancer. Recent advances in virology and molecular biology have made possible the engineering of recombinant virus with specific properties, creating new interest in virus-based therapy of solid tumors. One promising approach is the use of genetically modified herpes simplex virus-1 (HSV-1) to treat central nervous system (CNS) malignancies (Mineta et al., 1995, Nature Med. 1:938-943; Martuzza et al., 1991, Science 252:854-856; Market et al., 1992, J. Neurosurg. 77:590-594; Randazzo et al., 1995, Virology 211:94-101; Kesari et al., 1995, Lab. Invest. 73:636-648). Mutant HSV-1 viruses, such as HSV-1716, HSV-3616, HSV-4009, HSV-3410 and HSV-G207 have a deletion or impaired function in the gene encoding ICP34.5 which is a major determinant of pathogenicity (MacLean et al., 1991, J. Gen. Virol. 72:630-639; Chambers et al., 1995, Proc. Natl. Acad. Sci. USA 92:1411-1415; Meignier et al., 1988, J. Infect. Dis. 158:602-614; Mineta et al., 1995, Nature Med. 1:938-943). Web site: http://www.delphion.com/details?pn=US06428968__
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Electrical stimulation apparatus and method Inventor(s): Mo; Y. Joseph (Princeton, NJ) Assignee(s): NexMed Holdings, Inc. (Robbinsville, NJ) Patent Number: 6,594,527 Date filed: April 2, 2001 Abstract: An electrical stimulation apparatus and method for providing electrical stimulation to tissue. The electrical stimulation apparatus includes a base unit and an electrode module. The base unit is configured to be hand portable and contains a first electrical circuit and a first battery for supplying electrical energy to the first electrical circuit. A second electrical circuit and a second battery provide a time/date function. The base unit supports an LCD to provide a visual indication of the various functions of the electrical stimulation apparatus. The electrode module is programmable to enable the prescribing physician to set the treatment protocol for the electrical stimulation apparatus. The present apparatus is particularly well suited for the treatment of herpes simplex and herpes zoster. Excerpt(s): This invention relates to the electrical stimulation of tissue for the treatment of selected physiological conditions and, more particularly, to a novel electrical stimulation apparatus and method having an interchangeable electrode module, the electrode module serving as an activation key and being preprogrammable to deliver a predetermined treatment protocol for the particular physiological condition. Various skin lesions such as those resulting from acne and herpes virus are known to be amenable to treatment through the use of electrical stimulation. Although various theories have been advanced to explain this phenomena, to date, no satisfactory explanation has been put forth as a rationale for why these types of skin conditions can be successfully treated using electrical stimulation. In spite of this lack of explanation, various devices have been developed for the delivery of electrical stimulation to tissue. For example, U.S. Pat. No. 5,117,826 teaches a device for the combined nerve fiber treatment and body stimulation while U.S. Pat. No. 5,133,352 teaches a method for treating herpes simplex. A small size, low frequency curing apparatus is shown in U.S. Pat. No. 4,922,906. An electrotherapeutic treatment apparatus is shown in U.S. Pat. No. 5,107,835. U.S. Pat. No. 4,913,148 discloses the treatment of herpes simplex I and II as well as herpes zoster. A low frequency electrotherapeutic device is disclosed in U.S. Pat. No. 5,133,351. Each of these devices apparently resulted from the search for a device that could be used for the various therapeutic purposes as disclosed in the description of the device and its intended use. It is clear from the foregoing that electrical stimulation can be beneficial if appropriately applied to the area requiring treatment. Appropriate application includes, for example, predetermining the correct voltage of the electrical stimulation, the pulse waveform, if any, the amperage, and the application duration, to name several. Clearly, each application requires that each of the foregoing elements of the electrical stimulation must be tailored to meet the specific requirements for each patient. Web site: http://www.delphion.com/details?pn=US06594527__
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Herpes simplex virus ORF P is a repressor of viral protein synthesis Inventor(s): Bruni; Renato (Chicago, IL), Roizman; Bernard (Chicago, IL) Assignee(s): Arch Development Corporation (Chicago, IL) Patent Number: 6,383,738 Date filed: December 7, 1998 Abstract: The present invention is directed to methods and compositions relating to the treatment of herpes simplex virus infections and the screening of compounds for activity that inhibit or promote viral latency. The previously identified ORF P gene product now has been shown to interact with certain eukaryotic splicing factors and, in a cell infected with a herpesvirus containing a derepressed ORF P gene, ORF P can limit the splicing of at least two viral products. Given this function, it now is possible to screen for inhibitors and inducers of ORF P and, further, provide methods for maintaining and preventing viral latency. Excerpt(s): The present invention relates to the fields of molecular and cell biology generally, and more specifically, it addresses mechanisms for growth control in eurkaryotic cells. In particular, there are provided viral genes that inhibit viral protein synthesis and methods for use thereof. Herpes simplex viruses, designated with subtypes 1 and 2, are enveloped viruses that are among the most common infectious agents encountered by humans, infecting millions of human subjects worldwide. These viruses cause a broad spectrum of disease which ranges from relatively insignificant to severe and life-threatening. Clinical outcome of herpes infections is dependent upon early diagnosis and prompt initiation of antiviral therapy. Despite some successful efforts in treating HSV infectious, dermal and epidermal lesion often recur, and HSV infections of neonates and infections of the brain are associated with high morbidity and mortality. Herpes simplex virus 1 (HSV-1) causes two kinds of infection. The first, exemplified most dramatically after first exposure to the virus, results in productive infection at the portal of entry of the virus into the body. In productive infection, approximately 80 different genes are expressed, viral protein and DNA are made, viral progeny is assembled and, ultimately, the cell is destroyed. The second type of infection, latent infection, takes place only in sensory neurons populated by viruses brought to that sites by retrograde transport along axons from the portal of entry. In latently infected cells, viral DNA is maintained as an episome, and the only products detected to date are transcripts arising from two copies of a 8.5 kB domain of the DNA. Recombinants lacking sequences encoding the promoters and 5' domains of these RNAs, however, are capable of establishing latent infections. These finding suggested that either as yet unknown viral gene products or cellular gene products are responsible for the establishment of the latent state (Roizman and Sears, 1995). Web site: http://www.delphion.com/details?pn=US06383738__
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Herpes simplex virus VP22 vaccines and methods of use Inventor(s): Burke; Rae Lyn (San Francisco, CA), Tigges; Michael A. (Oakland, CA) Assignee(s): Chiron Corporation (Emeryville, CA) Patent Number: 6,635,258 Date filed: May 26, 1998
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Abstract: Vaccines containing herpes simplex virus (HSV) VP22 polypeptides capable of eliciting a cellular immune response and methods for treating and preventing HSV infections using the vaccines are disclosed. The vaccines can include additional HSV polypeptides, such as HSV glycoproteins. Also disclosed are methods of DNA immunization. Excerpt(s): The present invention relates generally to herpesvirus vaccine compositions. In particular, the invention pertains to vaccines containing VP22 polypeptides and methods for treating and preventing herpes simplex virus infections using the vaccines. Herpes simplex virus (HSV) infections are extremely prevalent and have a range of manifestations from apparently asymptomatic acquisition to severe disease and lifethreatening infections in the immunocompromised individual and the neonate. These infections are caused by two viruses, herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). HSV-1 is the predominant cause of oral infections and is usually acquired in childhood, whereas HSV-2 infections are usually sexually transmitted genital infections. These distinctions are blurred, however, and up to 25% of genital herpes is caused by HSV-1. Following initial infection, the virus establishes a life-long latent state and periodically reactivates, causing clinically apparent lesional episodes or asymptomatic virus shedding. Despite the availability of the antiviral agent, acyclovir, the incidence of HSV-2 in the population ranges from 8-50% and is increasing. The apparent reason for this increase is that most individuals are unaware of their infection. Moreover, the majority of transmission occurs from virus shed asymptomatically. Web site: http://www.delphion.com/details?pn=US06635258__ •
Herpes simplex virus-1 deletion variants and vaccines thereof Inventor(s): Brown; Susanne M. (Glasgow, GB), MacLean; Alasdair R. (Glasgow, GB) Assignee(s): The University Court of the University of Glasgow (Glasgow, GB) Patent Number: 6,423,528 Date filed: June 16, 1999 Abstract: Novel Herpes simplex viruses and vaccines based on such novel HSV-1 strains are described. In particular, viruses having a deletion in the terminal portion of R.sub.L are provided. The virus can be further modified to express heterologous antigens and also engineered to overproduce HSV Light particles. This is achieved by incorporating a ts mutation into the UL26 gene. Excerpt(s): This invention relates to variants of herpes simplex virus type 1 (HSV-1) which lack neurovirulence. Such variants are of value in the preparation of live attenuated vaccines for the prevention of HSV infections in humans. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are important human pathogens which infect more than 80% of the general population and cause recurrent mucocutaneous lesions. Following replication HSV enters the peripheral nervous system where active replication is turned off by an unknown mechanism. Thereafter a latent infection in neurons is established which persists for the life of the host. HSV can reactivate from the latent state to produce infectious lesions. HSV is responsible for a broad spectrum of clinical diseases ranging from relatively benign cutaneous lesions to fatal viral encephalitis. A considerable amount of research has already been devoted to elucidation of the genetic organisation of both HSV-1 and HSV-2. The HSV-1 genome is a linear double stranded DNA molecule of approximately 152 kilobase pairs consisting of two
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components L and S. Each component consists of unique sequences U.sub.1 and U.sub.s, flanked by inverted repeats. The organisation of the HSV-2 genome is similar but not identical. For a detailed description of the genetic organisation of HSV-1 and HSV-2 (see McGeoch, 1987). Web site: http://www.delphion.com/details?pn=US06423528__ •
HIgR and related domain which binds glycoprotein D of herpes simplex virus Inventor(s): Cocchi; Francesca (Sasso Marconi, IT), Fiume; Gabriella Campadelli (Bologna, IT), Lopez; Marc (Marseilles, FR), Menotti; Laura (Bologna, IT) Assignee(s): Inserm Institut National de la Sante et de la Recherche Medicale (Paris, FR), Universita' Degli Studi di Bologna (Bologna, IT) Patent Number: 6,469,155 Date filed: November 9, 1999 Abstract: The present invention relates to an immunoglobulin-like protein useful in preventing or treating pathologies concerned with herpes simplex virus 1, herpes simplex virus 2 infections in humans. Excerpt(s): The present invention relates to HIgR (herpesviris immunoglobulin-like receptor) for the manufacture of medicaments for preventing or treating HSV-1, HSV-2 infections. The present invention also relates to a novel immunoglobulin-like protein and medicaments which incorporate said antibodies and are useful in preventing or treating pathologies concerned with herpes simplex virus 1, herpes simplex virus 2 infections in humans. The invention also relates to methods for obtaining cell lines resistant to HSV-1, HSV-2 and BHV-1 infections and to cell lines expressing specific receptors which mediate entry of said virus within cellular environment to test efficacy of antiherpes drugs and antibodies, antiherpesvirus vaccines and herpesvirus-based vectors. Alphaherpesviruses which includes HSV-1, HSV-2, PRV, and BHV-1, infect a variety of cells resulting in efficient virus production in a short replicative cycle. Infection in the mammals results in lesion of the mucocutaneous tissue, and specifically in humans produces lesion on the mucosal surfaces, with spread of virus to the nervous system and establishment of latent infections in neurons. Infections may lead in some cases, to encephalitis or meningitis, with an often fatal outcome. Web site: http://www.delphion.com/details?pn=US06469155__
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Identification of a transforming fragment of herpes simplex type 2 and detection thereof in clinical specimens Inventor(s): Coutlee; Fran.cedilla.ois (Montreal, CA), Dipaolo; Joseph A. (Bethesda, MD), Kessous; Allegria (Cote St-Luc, CA) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC), Universite de Montreal () Patent Number: 6,617,103 Date filed: August 13, 1999 Abstract: The present invention relates to oligonucleotide probes derived from HSV-2, capable of selectively hybridizing thereto and to a subsequence of HSV-2 BglII N from which the oligonucleotide probes were derived. Further, the invention relates to an
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optimized assay of nudeic acid amplification permitting the sensitive and specific detection in clinical specimens of HSV-2 as well as a specific typing of the HSV in the sample. The present invention further relates to kits for the detection and typing of the HSV in a sample. In addition, the invention provides the nucleic acid and amino acid sequence of a subsequence of HSV-2 BglII N having transforming activity. Further, the invention teaches diagnostic and therapeutic methods for genital cancer comprising the use of these sequences or ligands directed thereto. Excerpt(s): The present invention relates to the detection of Herpes Simplex type 2 (HSV-2), more particularly, the invention relates to a transforming fragment of HSV-2 and to the detection thereof in clinical specimens. Nearly one fifth of adults in the United States are infected with herpes simplex virus type 2 (HSV-2). Although HSV-2 is the most common cause of genital ulceration in developed countries, subclinical HSV-2 infections are suspected to affect a more important proportion of infected individuals. HSV-2 has also been proposed as a causative agent of genital cancer (Guibinga et al., 1995, Arch. STD/HIV Res. 9:163-179). However conflicting results from in vitro and in vivo studies have shed doubts on the role of this agent in cancer of the uterine cervix (Guibinga et al., 1995, Arch. STD/HIV Res. 9:163-179). A transforming region of the HSV-2 genome--the 7.6 kb BglII N (m.u. 0.58-0.63) segment--has been identified, using transfection experiments. This was further supported by studies showing that BglII N sequences can also cooperate with oncogenic papillomas viruses to transform cells (DiPaolo et al., 1990, Virol. 777-779). Initially, the transforming ability of HSV-2 was thought to be located on the left-end (Xho-3 subfragment) of the BglII N segment (Galloway et al., 1983, Nature 392:21-24; Ibid., 1984, Proc. Natl. Acad. Sci. USA 81:47364740). However, neither the presence of a viral protein (Galloway et al., 1982, J. Virol. 42:530-537; Vonka et al., 1987, Adv. Cancer Res. 48:149-191) nor the persistence or integration (Galloway et al., 1983; Vonka et al., 1987) of specific HSV sequences, seemed to be required for the maintenance of the transformed phenotype (Pilon et al., 1989, Biochem. Biophys. Res. Comm. 159:1249-1261). The transforming ability of HSV-2 was left unexplained. Transfection of NIH 3T3 cells with the right-end (Kessous-Elbaz et al., 1989, J. Gen. Virol. 70:2171-2177; Pilon et al., 1989; Saavedra et al., 1985, EMBO J. 4:34193426) of the BglII N fragment (the Xho-1 and Xho-2 subfragments) showed an increase in the number of transformed foci, and HSV-2 sequences were retained more efficiently in transformed cells (Kessous-Elbaz et al., 1989; Pilon et al., 1989; Saavedra et al., 1985). A number of clinical and epidemiologic studies have concluded that high risk papillomaviruses, such as HPV-16 and HPV-18 are necessary for the development of cervical cancer, but the long delay following infection indicates the importance of other factors (Kessler, 1986, In: Viral Etiology of Cervical Cancer, Peto et al., Eds. Cold Spring Harbor, N.Y., 55-64; and, zur Hauzen, 1989, Cancer Research 49:46774681), particularly other sexually transmitted infections (Kaufman et al., 1986, Clin. Obstet. Gynecol. 29:678-698; Macnab et al., 1989, Biomed. and Pharmacother. 43:167-172; zur Hausen, 1982, Lancet 2:1370-1372), for the development of malignancy. Although the etiologic link between herpes simplex virus-2 (HSV-2) and cervical cancer was proposed over two decades ago, the significance of the importance of HSV-2 to cervical cancer has been rather recent. The role for HSV-2 infection has been based primarily on seroepidemiological data (Nahmias et al., 1970, Am. J. Epidemiol. 91:547-552; Rawls et al., 1968, Am. J. Epidemiol. 87:647-656) and on observation of viral antigens in exfoliated cells from patients with cervical dysplasia and cancer (Royston et al., 1970, Proc. Nat. Acad. Sci. 67:204-212). The difficulty in establishing a strong association was compounded by the lack of persistence of HSV sequences in the neoplastic cervical lesions (Macnab et al., 1989, Biomed. and Pharmacother. 43:167-172). In fact, in a prospective case-control study (Vonka, 1984, Int. J. Cancer 33:61-65) the investigators
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failed to observe such an association, which was later suggested may have resulted from overmatching of the cohort of women for sexual activity that minimized the risk factor (Reeves et al., 1989, New Engl. J. Med. 320:1437-1441). In other studies the lack of correlation of HSV-2 with cervical cancer was attributed to the use of immunoglobulin G instead of immunoglobulin A as a marker for the presence of HSV-2 (Corbino et al., 1989, Eur. J. Gynaecol. Oncol. 10:103-108). Web site: http://www.delphion.com/details?pn=US06617103__ •
Immunogenic composition of interleukin-12 (IL-12), alum, herpes simplex viral (HSV) antigen, and method thereof Inventor(s): Eldridge; John H. (Fairport, NY), Mishkin; Eric M. (Monroe, NY) Assignee(s): Wyeth (Madison, NJ) Patent Number: 6,488,936 Date filed: February 10, 1999 Abstract: This invention pertains to vaccine compositions comprising a mixture of antigen, such as a herpes simplex virus antigen, and the interleukin IL-12, which may be adsorbed onto a mineral in suspension. These vaccine compositions modulate the protective immune response to the antigen. Excerpt(s): The immune system uses many mechanisms for attacking pathogens; however, not all of these mechanisms are necessarily activated after immunization. Protective immunity induced by vaccination is dependent on the capacity of the vaccine to elicit the appropriate immune response to resist or eliminate the pathogen. Depending on the pathogen, this may require a cell-mediated and/or humoral immune response. The current paradigm for the role of helper T cells in the immune response is that T cells can be separated into subsets on the basis of the cytokines they produce, and that the distinct cytokine profile observed in these cells determines their function. This T cell model Includes two major subsets: TH-1 cells that produce IL-2 and interferon.gamma. (IFN-.gamma.) which augment both cellular and humoral immune responses, and TH-2 cells that produce IL-4, IL-5 and IL-10 which augment humoral immune responses (Mosmann et al., J. Immunol. 126:2348 (1986)). It is often desirable to enhance the immunogenic potency of an antigen in order to obtain a stronger immune response in the organism being immunized and to strengthen host resistance to the antigen-bearing agent. A substance that enhances the immunogenicity of an antigen with which it is administered is known as an adjuvant. For example, certain lymphokines have been shown to have adjuvant activity, thereby enhancing the immune response to an antigen (Nencioni et al., J. Immunol. 139:800-804 (1987); EP285441 to Howard et al.). This invention pertains to vaccine compositions comprising a mixture of herpes simplex virus glycoprotein D, the interleukin IL-12 and a mineral in suspension. The IL-12 may be either adsorbed onto the mineral suspension or simply mixed therewith. In a particular embodiment of the invention, the IL-12 is adsorbed onto a mineral suspension such as alum (e.g., aluminum hydroxide or aluminum phosphate). In a particular embodiment, the IL-12 is human IL-12. The invention also pertains to vaccine compositions which further comprise a physiologically acceptable vehicle. The invention further relates to immunogenic compositions comprising a mixture of a herpes simplex virus glycoprotein D, an adjuvant amount of interleukin12, a mineral in suspension, and optionally comprising a physiologically acceptable vehicle.
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Web site: http://www.delphion.com/details?pn=US06488936__ •
Immunogenic conjugated polypeptide for treatment of herpes simplex virus Inventor(s): Rosenthal; Kenneth S. (Akron, OH), Zimmerman; Daniel H. (Bethesda, MD) Assignee(s): CEL-SCI Corporation (Vienna, VA) Patent Number: 6,572,860 Date filed: March 30, 2000 Abstract: Peptide constructs chemically synthesized to contain a Herpes Simplex Virus specific antigenic peptide, such as, the 322-332 peptide (H1) from the ICP27 protein of Herpes Simplex Virus (HSV-1) and a peptide from a T cell binding ligand (TCBL), such as.beta.-2M (aa 35-50), which elicits a TH1-like response in vitro tests in mice, were protective against challenge with HSV. Excerpt(s): This invention relates to peptide conjugates which can be used to form an immunogenic composition useful to activate the immune system of a patient exposed to or at risk of infection by Herpes Simplex Virus (HSV). More particularly, this invention relates to immunogenic conjugated peptides which contain both a herpes simplex virus specific peptide and an immunomodulatory peptide covalently linked directly or via a linking group and to compositions and diagnostic products containing and methods using such peptide conjugates in the treatment, prevention, or diagnosis of herpes simplex virus. Herpes simplex virus type 1 (HSV-1) and its close cousin, herpes simplex virus type 2 (HSV-2), cause various benign diseases, such as the common cold sore found near the lips and also genital herpes. Herpes simplex virus can also cause serious disease upon infection of the eye (e.g., keratoconjunctivitis, with the potential to lead to blindness), the brain (e.g., encephalitis). Individuals who are immunosuppressed, such as a newborn baby, AIDS patient or transplant patient, are especially vulnerable. HSV infections of immunocompromised individuals and neonates can lead to disseminated and life-threatening disease. Unlike many viruses, once an individual is infected with HSV, the virus remains latent in neurons and can be reactivated by stress or immunosuppression and cause recurrent disease. A herpes simplex virus vaccine has the potential for use as both a prophylactic to prevent initial infection as well as a treatment to prevent or ameliorate recurrent disease. No vaccine is currently available for prevention or treatment of HSV. Live vaccine development has been hampered because HSV has the capacity to establish latent infection and potentially, to promote neoplastic transformation of cells. The efficacy of live attenuated killed and subunit vaccines has been questioned due to difficulties in eliciting protective cell mediated immune responses. Web site: http://www.delphion.com/details?pn=US06572860__
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Immunological herpes simplex virus antigens and methods for use thereof Inventor(s): Corey; Lawrence (Seattle, WA), Koelle; David M. (Seattle, WA) Assignee(s): University of Washington (Seattle, WA) Patent Number: 6,375,952 Date filed: August 5, 1999
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Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection. Excerpt(s): Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention pertains. The invention relates to molecules, compositions and methods that can be used for the treatment and prevention of herpes simplex virus (HSV) infection. More particularly, the invention identifies epitopes of HSV proteins that can be used for the development of methods, molecules and compositions that stimulate or augment HSV-specific immunity. The complete, known DNA sequence of HSV types 1 and 2 are approximately 160 kb and encodes about 85 genes, each of which encodes at least one protein. Unknown are the immunological epitopes within these proteins, each epitope approximately 9-12 amino acids in length, that are capable of eliciting an effective T cell immune response to viral infection. Cellular immune responses are required to limit the severity of recurrent HSV infection in humans. HSV-specific CD4 T cells can be cytotoxic towards virally-infected cells (M. Yasukawa et a., 1991, J. Immunol., 146:1341-1347; M. Yasukawa et al., 1984, J. Immunol., 133:2736-42). HSV-specific T cells can also reduce the titer of HSV replication in HSV-infected, HLA-matched cells, produce lymphokines with antiviral or immunomodulatory activity, or provide specific B cell help to augment antiviral antibody responses. References relating to the antigenic specificity of HSVspecific T cells include: A. G. Langenberg et al., 1995, Ann. Int. Med. 122:889-898; A. Mikloska et al., 1998, J. Gen. Virol., 79:353-361; J. W. Torseth et al., 1987, J. Virol., 61:15321539; M. Yasukawa et al., 1985, J. Immunol., 134:2679-2687. Web site: http://www.delphion.com/details?pn=US06375952__ •
Method and reagent for inhibiting herpes simplex virus replication Inventor(s): Draper; Kenneth G. (Boulder, CO) Assignee(s): Ribozyme Pharmaceuticals, Inc. (Boulder, CO) Patent Number: 6,432,704 Date filed: June 28, 1999 Abstract: An enzymatic RNA molecule which specifically cleaves a herpes simplex virus mRNA molecule. Excerpt(s): This invention relates to reagents useful as inhibitors of herpes simplex virus (HSV) replication and gene expression. The following is a discussion of relevant art, none of which is admitted to be prior art to the pending claims. Human herpesviruses cause a wide variety of diseases which result in significant levels of morbidity and mortality worldwide. The HSV group accounts for about one million new cases of infection each year in the United States. These infections are maintained for the lifetime of the patient as latent viral infections, which can be stimulated to reactivate by a variety
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of factors. The manifestations of HSV infection range from mild infections of herpes labialis to more serious infections such as herpes encephalitis. Web site: http://www.delphion.com/details?pn=US06432704__ •
Method and topical treatment composition for herpesvirus hominis Inventor(s): Squires; Meryl (Elmhurst, IL) Assignee(s): Squires; Meryl J. (Barrington Hills, IL) Patent Number: 6,348,503 Date filed: February 12, 1996 Abstract: Improved topical treatment of active phase lesions resulting from recurrent viral infection by herpes simplex virus which includes the use of two primary agents, namely, an aqueous solution of benzalkonium halide, preferably benzalkonium chloride, and a dry form of the herb Echinacea purpurea, preferably in powder form. Active phase herpes lesions are wetted with the benzalkonium chloride solution and dusted with the powder form of Echinacea purpurea to create a coating on the wetted lesion surface. The coating is maintained on the lesion throughout treatment, and unexpected rapid resolution of the lesions results. Excerpt(s): The present invention generally relates to methods and compositions for the treatment of herpes simplex virus and, in particular, to a method and composition for topical treatment of active phase lesions resulting from recurrent viral infection caused by herpes simplex virus. Recurrent viral infection by herpes simplex virus, also known as Herpesvirus Hominis, is characterized by lesions which may appear anywhere on the skin or mucosa. Eventually, the lesion base inflames and develops clusters of small fluid-filled vesicles. Without treatment, the vesicles and lesions will resolve in several days to dry scabs. There are two known strains of herpes simplex virus (HSV), namely, HSV-1, commonly causing herpes labialis and keratitis, and HSV-2, which is usually genital herpes. Treatment of herpes lesions often includes application of topical agents such as idoxuridine, trifluorothymidine, or acyclovir. In addition, prior art patents also disclose various compositions and methods for topical treatment of symptoms of herpes simplex virus which may include use of anti-viral agents, such as benzalkonium chloride, e.g., U.S. Pat. Nos. 4,283,421, 4,585,656, 4,661,354, 4,760,079, 4,803,224 and 4,797,420. None of these compositions, however, employ the combination of treatment agents disclosed herein. Web site: http://www.delphion.com/details?pn=US06348503__
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Methods for electrokinetic delivery of medicaments Inventor(s): Henley; Julian L. (Guilford, CT) Assignee(s): Biophoretic Therapeutic Systems, LLC (Framingham, MA) Patent Number: 6,385,487 Date filed: December 4, 1998 Abstract: Drugs and a portable iontophoresis apparatus for facilitating delivery of the drugs across the cutaneous membrane into adjacent underlying tissues and blood vessels. The apparatus employs a modular, detachable non-reusable medicamentcontaining applicator electrode which is adapted to attach to a base assembly. The
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apparatus is designed to be hand-held and includes a circumferential tactile electrode band on the base assembly which provides electrical connection between the skin of the user's hand and one pole of a bipolar power source housed within the base assembly. The opposing pole of the power source is connected to the applicator electrode. When the applicator is placed against the skin of a user, the user's body completes the electrical circuit between the applicator and tactile electrodes. The apparatus employs a disposable applicator electrode which accepts a variety of antimicrobial and anesthetic agents for transdermal iontophoretic or ionosonic delivery. A method for using the device for the treatment of Herpes simplex infection and related viral infections which produce similar cutaneous lesions is presented. The apparatus, when used in accordance with the antiviral medicaments and method described herein, demonstrated >90% treatment efficacy in clinical trials. Excerpt(s): This invention relates generally to the transdermal electrokinetic mass transfer of medication into a diseased tissue and, more specifically, to iontophoretically transportable agents and a portable apparatus for the iontophoretic delivery of medication, including antimicrobial and anesthetic agents, across the skin. The apparatus provides a new method for treating and managing diseases presenting cutaneous lesions and administering anesthesia. Iontophoresis has been employed for several centuries as a means for applying medication locally through a patient's skin and for delivering medicaments to the eyes and ears. The application of an electric field to the skin is known to greatly enhance the skin's permeability to various ionic agents. The use of iontophoretic transdermal delivery techniques has obviated the need for hypodermic injection for many medicaments, thereby eliminating the concomitant problems of trauma, pain and risk of infection. Iontophoresis involves the application of an electromotive force to drive or repel oppositely charged ions through the dermal layers into a target tissue. Particularly suitable target tissue includes tissues adjacent to the delivery site for localized treatment or tissues remote therefrom in which case the medicament enters into the circulatory system and is transported to a tissue by the blood. Positively charged ions are driven into the skin at an anode while negatively charged ions are driven into the skin at a cathode. Studies have shown increased skin penetration of drugs at anodic or cathodic electrodes regardless of the predominant molecular ionic charge on the drug. This effect is mediated by polarization and osmotic effects. Web site: http://www.delphion.com/details?pn=US06385487__ •
Methods for identifying cell cycle regulators Inventor(s): Brown; Susanne M. (Glasgow, GB), Harland; June (Glasgow, GB), Maclean; Alasdair R. (Glasgow, GB) Assignee(s): The University Court of the University of Glasgow (Glasgow, GB) Patent Number: 6,641,995 Date filed: December 29, 2000 Abstract: A method is disclosed for identifying a substance capable of disrupting an interaction between (i) a herpes simplex virus (HSV) ICP34.5 polypeptide or a homologue thereof, or a derivative thereof, and (ii) proliferating cell nuclear antigen (PCNA) or a homologue thereof, or a derivative thereof, which method comprises: (a) providing an HSV ICP34.5 polypeptide or a homologue thereof, or a derivative thereof, as a first component; (b) providing PCNA, or a homologue thereof, or a derivative thereof, as a second component; (c) contacting the two components with a substance to
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be tested under conditions that would permit the two components to interact in the absence of the said substance; and (d) determining whether the said substance disrupts the interaction between the first and second components. Excerpt(s): This invention relates to methods for identifying substances capable of regulating the cell cycle. It further relates to the use of said substances in treating or preventing viral infection, cancer or cell death. Herpes simplex virus (HSV) has a virulence determining locus in the long repeat region of its genome (Ackermann et al., 1986; Chou and Roizman, 1990; McGeoch et al., 1991; Dolan et al., 1992). The virulence phenotype has been specifically assigned to the RL1 gene and its encoded protein ICP34.5 (McKie et al., 1994). Null mutants in ICP34.5 are totally avirulent in mice (Taha et al., 1989a, b; Chou et al., 1990; MacLean et al., 1991) and the function of the protein in vitro has been shown to be cell type and cell state specific, depending on the stage in the cell cycle and the differentiation state (Brown et al., 1994). One ICP34.5 function demonstrated in a human neuroblastoma cell line is the preclusion of host cell protein synthesis shut-off via the protein kinase PKR pathway following HSV infection (Chou and Roizman, 1992; Chou et al., 1995). This response to expression of ICP34.5 is however not ubiquitous and the precise molecular functions of ICP34.5 remain unknown. Web site: http://www.delphion.com/details?pn=US06641995__ •
Methods for treating subjects infected with a herpes virus Inventor(s): Docherty; John (Kent, OH), Tsai; Chun-che (Kent, OH) Assignee(s): Kent State University (Kent, OH), Northeastern Ohio Universities College of Medicine (Rootstown, OH) Patent Number: 6,599,945 Date filed: August 15, 2001 Abstract: The present invention provides a method of inhibiting the formation of infectious herpes virus particles, particularly infectious herpes simplex virus (HSV) particles, in a host cell. The method involves administering an effective amount of a hydroxylated tolan, particularly a polyhydroxylated tolan, to a herpes virus infected host cell. The present invention also provides a method of treating a herpes virus infection, particularly an HSV infection. The method comprises administering a topical composition comprising a therapeutically effective amount of a hydroxylated tolan to a herpes virus-infected site. The present invention also relates to a topical composition for treating a herpes virus infection selected from the group consisting of an HSV infection, a cytomegalovirus infection, and a varicella zoster virus infection. The present invention also provides a method of treating a subject infected with Neisseria gonorrhea. Excerpt(s): The present invention relates to compositions which inhibit replication of herpes virus and the bacterium Neisseria gonorrheae, and methods of using such compositions to treat subjects infected with these microorganisms. Human herpes viruses can infect host cells in virtually any organ of the human body. Replication of a herpes virus within an infected host cell leads to lysis of the infected cell and the release of large numbers of infectious virus. The infectious particles released from the lysed cell can infect and destroy other cells at or near the site of the initial infection. These infectious particles can also be transmitted to a non-infected individual. Human herpes viruses can also enter and remain latent, i.e., in the non-replicative state, in other cells of the afflicted individual for life. This life-long infection serves as a reservoir of infectious virus for recurrent infections in the afflicted individual and as a source of infection for
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an unwitting contact. At least four of the human herpes viruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and varicella zoster virus (VZV) are known to infect and cause lesions in the eye of certain infected individuals. Together, these four viruses are the leading cause of infectious blindness in the developed world. Web site: http://www.delphion.com/details?pn=US06599945__ •
Nucleoside analogs in combination therapy of herpes simplex infections Inventor(s): Boyd; Malcolm Richard (Epsom, GB) Assignee(s): Novartis International Pharmaceutical Ltd. (Hamilton, BM) Patent Number: 6,514,980 Date filed: July 26, 2000 Abstract: A pharmaceutical product comprising a nucleoside analogue active against herpes simplex virus, such as acyclovir/valaciclovir or penciclorivir/famciclovir, and an immunosuppressant, as a combined preparation for simultaneous, separate or sequential use in the treatment and/or prevention of herpes simplex virus infections. Excerpt(s): This invention relates to the use of a nucleoside analogue active against herpes simplex virus (HSV), in the treatment of herpes simplex virus infections, and to pharmaceutical compositions containing the two components. The disease indication for herpes simplex subtype 1 (HSV-1) is herpes labialis (cold sores), and the disease indication for herpes simplex subtype 2 (HSV-2) is genital herpes. Herpes Labialis is a common world-wide disease characterized by repeated attacks of versicular eruptions most commonly recognised on the lips and perioral skin. Many patients report pain, swelling and significant cosmetic concerns associated with subsequent ulceration of lesions. Although generally a minor disease, in some patients the consequences of frequent severe attacks can be debilitating. The disease is naturally self-limiting in immunecompetent individuals and recurrent episodes last 7-10 days. Web site: http://www.delphion.com/details?pn=US06514980__
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Pharmaceutical composition of escherichia coli heat-labile enterotoxin adjuvant and methods of use Inventor(s): Clements; John D (New Orleans, LA) Assignee(s): The United States of America as represented by the Secretary of the Navy (Washington, DC) Patent Number: 6,413,523 Date filed: February 23, 1995 Abstract: Novel immunoregulatory utilities of Escherichi coli heat-labile enterotoxin (LT) are disclosed. This enterotoxin can be used in combination with an unrelated antigen to achieve a higher immune response to said antigen when administered as part of an oral vaccine preparation. By way of example, the efficacy of oral adjuvant therapy of LT in the development of immunological protection against herpes simplex virus was examined. In addition, the ability of LT to influence the induction and maintenance of tolerance in animals primed orally with two unrelated protein antigens administered simultaneously, OVA and BSA was examined. Simultaneous administration of LT with
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OVA was shown to prevent the induction of tolerance to OVA and to increase the serum anti-OVA IgG response to 30-90 fold over PBS primed and OVA primed animals, respectively. Excerpt(s): Oral immunization can lead to loss of systemic reactivity in response to subsequent parenteral injection of the specific antigen (Challacombe and Tomasi, 1980, J. Exp. Med. 152:1459-1472). This phenomenon of immune tolerance after ingestion of antigen has been shown to occur in numerous animal models. A variety of effects may account for this phenomenon, including (a) antigen overload, (b) induction of antigenspecific suppressor T cells, and (c) clonal deletion of antigen-specific T and B cells [recently reviewed by Siskind] (Siskind, 1984, In: Fundamental Immunology (Ed. Paul) Raven Press, New York, pp. 537-558). The abrogation of tolerance (or prevention of its induction) has also been widely examined (Green and Ptak, 1986, Immunol. Today 7:8187; La Tont, et al., 1982, J. Exp. Med. 142:1573-1578; Suzuki, 1986, Nature 320:451-454). In general, it has been observed that the the ability to influence induction of tolerance depends upon the cellular basis of the state of tolerance. Tolerance can be either complete or partial, and is influenced by antigen dose and characteristics, route of administration, physiological state of the organism, and genetic characteristics of the organism. It has also been shown that tolerance can be terminated or prevented by various manipulations, depending upon the cellular basis of the state of tolerance. Recently it has been demonstrated that administration of cholera toxin (CT) can abrogate oral tolerance to an unrelated antigen (Elson and Ealding, 1984a, J. Immunol. 132:2736-2741). CT, an 84,000 dalton polymeric protein produced by Vibrio cholerae, consists of two subunits, designated A and B. The 56,000 dalton B subunit binds the toxin to its cell surface receptor, the monosialosylganglioside G.sub.M1, and facilitates the penetration of the toxic 28,000 dalton A subunit into the cell. The A subunit catalyzes the ADP-ribosylation of the stimulatory GTP-binding protein (G.sub.S) in the adenylate cyclase enzyme complex and this results in increasing intracellular levels of adenosine 3', 5'-cyclic monophosphate (cAMP) (Finkelstein, 1973, CRC Crit. Rev. Microbiol. 2:553623; In Mechanisms of Bacterial Toxinology (Ed. Bemheimer) John Wiley and Sons, Inc., New York, pp. 53-84). Some strains of Escherichia coli produce an immunologically and structurally related heat-labile enterotoxin (LT) that has the same subunit organization and arrangement as CT and that works by the same 20 mechanism of action (Clements and Finkelstein, 1979, Infect. Immun. 24:760-769; Clements et al. 1980, Infect. Immun. 29:91-97). Although there are many similarities between CT and LT, there are also immunologic and structural differences between the two toxins (Clements and Finkelstein, 1979; Clements et al., 1980). It should be noted that the relative immunoregulatory potential of LT has not been thoroughly investigated. Recently, a clone of E. coli that produces only the binding subunit of the LT toxin (LT-B) was developed (Clements et al., 1983, Infect. Immun. 40: 653-658; Clements and El-Morshidy, Infect. Immun. 46: 564-569). Escherichia coli heat-labile enterotoxin and heat-stable enterotoxin have previously been used in compositions that are effective in providing immunologic protection in mammals against acute diarrheal disease caused by enterotoxigenic strains of E. coli. See U.S. Patents 4,053,584; 4,314,993; and 4,411,888 which are incorporated herein by reference; and Frantz et al., 1987, Infect. Immun. 55: 1077-1084, Hussaini and Sawtell, 1986, Dev. Biol. Stand. 64: 261-269. Web site: http://www.delphion.com/details?pn=US06413523__
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Phototherapeutic inactivation of ocular viruses Inventor(s): Crean; David H. (Santa Barbara, CA), Kupperman; Baruch D. (Laguna Beach, CA) Assignee(s): PDT Systems, Inc. (Santa Barbara, CA), The Regents of the University of California (Oakland, CA) Patent Number: 6,586,419 Date filed: April 16, 1997 Abstract: A method for inactivating ocular viral pathogens and for treating associated lesions on tissue by means of selectively activating a tissue-associated photosensitizing agent with light. The photosensitizing agent, preferably tin ethyl etiopurpurin, is administered to a patient to concentrate within the lesionous target tissue of the eye. The photosensitizer-laden target tissue is irradiated with photoactivating light. In preclinical in vitro studies, the photoactivated photosensitizer drug within the lesionous target tissue inactivates both cell free Herpes simplex virus (HSV) and cell-associated HSV and cytomegalovirus (CMV). The use of PDT for treating ocular viral diseases reduces the toxicity to the biological system when compared with prior art therapeutic procedures. Excerpt(s): This invention describes a method for treating ocular viral diseases using photodynamic therapy. In order to give a clinical perspective to the significance of viral ocular infections, for example, cytomegalovirus (CMV) retinitis is the most common ocular apportunistic infection and the leading cause of blindness in patients having Acquired Inmune Deficiency Syndrome (AIDS) 30,000 new case being each year in the United States alone. CMV related retinitis has been fond in 30% of AIDS patents, typically late in their diseases processes. The drugs, ganciclovir, and foscarnet, are effective in the treatment of CMV retinitis. With 82%-100% of patents exhibit an initial response to therapy with either drug. All three drugs are virostatic and require daily systemic intravenous administration for the remainder of the patients lives. Such systemic intravenous administration requires the use of an indevelling catheter which has been associated with high rates of infection. In addition all three drugs exhibit various systemic toxicity; with ganciclovir suppressing the bone marrow and both anywhere and foscarnet causing renal toxicity. The use of these compounds for untying ocular retinitisis discussed by Kupparmann, et al. in Ann I Opthalmol, 1993; 115:575-582; and by Holland et al. in Ophthalmol 1987; 94:815-823, and by Caleri et al in Ann. Intern. Med. 1977 126;257-263, A further discussion of the use of theses drugs for treating a retinitis of viral etiology is presented by various AIDS research groups in the New England journal of medicine, 1992; 326; 213-220. Prior to the advent of antiviral therapy (both anti-CMV and anti-HIV) AIDS patients wit CMV retinitis typically survived only 6 weeks after developing the latter infection. In the current setting of anti-HIV therapy and anti-CMV therapy, median survival has recently been shown to be 8.5 months for patients receiving ganciclovir and 12.6 months for patients receiving foscarnet and more recent studies suggest that median survival is now approaching two years. Longer survival has been associated with greater difficulty related to the continuous suppression of the retinitis over this extended period. Recurrence of the retinitis while on therapy has been reported to occur in 50% of patients within 3 months. (Gross, et al. Ophthalmol. 1990; 97:681-686.) Because of the high incidence of reactivation following the initial favorable response to therapy, the current measure of anti-CMV drug efficacy is based on the length of time to recurrence in addition to the initial therapeutic response to the drug. The fact that the efficacy of anti-CMV agents is, in part, measured by the agents' ability to prolong the interval for viral reactivation rather than by its
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ability to effect permanent suppression of viral activity emphasizes the marginal clinical effectiveness of current regimens wherein ganciclovir, acyclovir and foscarnet are administered intravenously. While these three drugs are preventing blindness in most AIDS patients, many patients are still losing their sight. A therapeutic procedure for controlling viral retinitis which reduces systemic toxicity over the current therapies is needed. Web site: http://www.delphion.com/details?pn=US06586419__ •
Production of recombinant proteins using herpes virus promoters and VP16 transactivators Inventor(s): Highkin; Maureen Katherine (St. Louis, MO), Hippenmeyer; Paul Jerome (St. Louis, MO) Assignee(s): G. D. Searle & Co. (Chicago, IL) Patent Number: 6,635,478 Date filed: April 30, 1996 Abstract: Stable cell lines are produced to express high levels of a gene product of interest using VP16, a herpes simplex virus transactivator, and a promoter from herpes simplex virus which is a target for VP16. The transactivator and promoter are introduced to a cell line separately using antibiotic resistance genes as selectable markers on separate vectors. Excerpt(s): This invention pertains to production of recombinant proteins and more particularly to a means of heterologous gene transactivation. The ability to efficiently produce recombinant proteins in mammalian cell culture is critical for the production of both research agents and commercial products. Several approaches and host vector systems for the production of recombinant proteins have been reviewed (Kaufman, Genetic Engineering, Principles and Methods, vol. 9, J. K, Setlow, ed., Plenum Press, New, York, 1987; Warren et al., Recombinant DNA Technology and Applications, A. Prokop, R. Bajpai and C. Ho, eds., McGraw Hill, New York, 1990). These systems include use of high copy episomal vectors such as bovine papillomavirus (Howley et al., Methods in Enzymology, vol. 101, Academic Press, New York, 1983), amplifiable vectors such as those containing the dihydrofolate reductase gene (Kaufman,supra), the asparagine synthetase gene (Andrulis, Molecular Cell Genetics, vol. 17, 1985) or the ornithine decarboxylase gene (McConlogue, Gene Transfer Vectors for Mammalian Cells. 1987) or strong constitutive promoters such as the simian virus 40 promoter (Mulligan et al., Science. vol. 209, pp. 1422-1427, 1980) or the human cytomegalovirus major early promoter (Boshart et al., Cell, vol. 41, pp. 521-530, 1985). All of these systems rely upon the levels of endogenous transactivators in the particular cell type to stimulate transcription of the promoters used to construct the expression vectors. An alternative approach to high level production would be to engineer cells with a specific transcriptional activator or transactivator. If the transactivator has a specific target promoter, then the target promoter can be linked to a gene of interest and inserted into the engineered cell. The amount of target protein produced from that cell would depend on several parameters. First, the inherent specific activity of the transactivator will be a factor in the amount of transcription from the target promoter. In addition, the amount of transactivator produced by the target cell will affect the amount of transactivation. For instance, in Chinese hamster ovary cells (CHO) there is a low level of endogenous glucocorticoid receptor/transactivator present. Transfection of a plasmid that requires the glucocorticoid receptor/transactivator results in very little expression from that
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plasmid. However, if the cells are first engineered to express high levels of the glucocorticoid receptor/transactivator, then high level expression from the same plasmid is obtained (Israel et al., Nuc. Acids Res., vol. 17, pp. 4589-4606, 1989). Therefore, the amount of transactivation depends on the amount of transactivator in the cell. The amount of transactivator will depend on the promoter used to drive expression of the transactivator and the site of the integration of the cassette in the host cell. Thirdly, the amount of target vector in a particular cell will influence how many copies will be transactivated. The site of integration of the target promoter may also play a role in the expression of the activated promoter. Web site: http://www.delphion.com/details?pn=US06635478__ •
Replication-competent herpes simplex virus Inventor(s): Parysek; Linda Marie (Cincinnati, OH), Pyles; Richard Brent (Cincinnati, OH), Warnick; Ronald E. (Loveland, OH) Assignee(s): The University of Cincinnati (Cincinnati, OH) Patent Number: 6,509,020 Date filed: September 22, 1999 Abstract: A promising approach for the therapeutic treatment of brain tumors utilizes replication-competent, neuroattenuated herpes simplex virus-1 (HSV-1) mutants. This approach requires mutation of HSV-1 to eliminate killing of normal, non-dividing cells of the brain (e.g., neurons). The present invention discloses methods for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the gamma 34.5 gene and the uracil DNA glycosylase (UNG) gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and is not neurovirulent. Excerpt(s): The present invention relates to recombinant virus strains capable of killing tumor cells. More specifically, the present invention relates to a mutated replicationcompetent viruses which contains mutations in two genes, is hypersensitive to antiviral agents such as ganciclovir, is not neurovirulent and does not replicate in non-dividing cells, yet can kill nervous system tumor cells. The present invention also relates to recombinant herpesvirus strains, vital vaccines incorporating such strains, methods for making such strains and vaccines, and methods for immunizing a human host against herpes simplex virus using the vaccines. Malignant tumors of the nervous system are generally fatal, despite many recent advances in neurosurgical techniques, chemotherapy and radiotherapy. In particular, there is no standard therapeutic modality that has substantially changed the prognosis for patients diagnosed with malignant brain tumors. For example, high mortality rates persist in malignant medulloblastomas, malignant meningiomas and neurofibrosarcomas, as well as in malignant gliomas. Gliomas are the most common primary tumors arising in the human brain. The most malignant glioma, the glioblastoma, represents 29% of all primary brain tumors, some 5,000 new cases per year in the United States alone. Glioblastomas are almost always fatal, with a median survival of less than a year and a 5-year survival of 5.5% or less. Mahaley et al., J. Neurosurg. 71: 826 (1989); Shapiro, et al., J. Neurosurg. 71: 1 (1989): Kim et al., J. Neurosurg. 74: 27 (1991). After glioblastomas are treated with radiotherapy, recurrent disease usually occurs locally; systemic metastases are rare. Hochberg et al., Neurology 30: 907 (1980). Neurologic dysfunction and death in an individual with glioblastoma is due to the local growth of the tumor.
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Sun-protection formulations active against herpes simplex viruses Inventor(s): Driller; Hansjurgen (Otzberg, DE), Hitzel; Sabine (Messel, DE) Assignee(s): Merck Patent Gesellschaft (Darmstadt, DE) Patent Number: 6,500,869 Date filed: September 12, 2000 Abstract: The invention relates to sun-protection formulations in solid or liquid form, containing organic and/or inorganic sunscreen filters having a prophylactic action against herpetic diseases of the skin, and to the use of said sun-screen formulations. Excerpt(s): The present invention relates to sunscreen formulations in solid or liquid form comprising organic and/or inorganic light protection filters having prophylactic action against herpetic diseases of the skin, and to the use of these sunscreen formulations. As is known, the skin is sensitive to solar rays, which can cause simple sunburn or an erythema, but also burns of varying severity. However, solar rays also have other negative effects: they cause the skin to lose its elasticity and form wrinkles, thus leading to premature ageing. Dermatoses may also sometimes be observed. In extreme cases, some people can develop skin cancer. Web site: http://www.delphion.com/details?pn=US06500869__
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Therapeutically effective substance mixture Inventor(s): Treusch; Gernot (Empuria Erava, Falconera 59, Castello d'Empories, ES) Assignee(s): none reported Patent Number: 6,448,227 Date filed: August 20, 2001 Abstract: A substance mixture, containing S-acetyl glutathione and Aciclovir, is effective as a medication against the Herpes Simplex virus and the Varicella Zoster virus. Excerpt(s): This invention relates to a mixture containing S-acetyl glutathione and Aciclovir (ACV) as medication against the Herpes Simplex virus or the Varicella Zoster virus. A process for the manufacture of S-acetyl glutathione is disclosed in U.S. Pat No. 2,760,956. Aciclovir (ACV) is a known medication for use against the Herpes Simplex virus (HSV). Aciclovir is an abbreviated nomenclature (INN) for 9-[(2hydroxyethoxy)methyl)guanine. Web site: http://www.delphion.com/details?pn=US06448227__
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Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections Inventor(s): Kristmundsdottir; Thordis (Seltjarnarnes, IS), Thormar; Halldor (Reykjavik, IS) Assignee(s): Lipomedica ehf. (Reykjavik, IS) Patent Number: 6,596,763 Date filed: December 16, 1999 Abstract: The present invention relates to a method for counteracting infections caused by bacteria, fungi or virus such as Herpes Simplex Virus in skin or mucosal membranes, in particular genital membranes, of a mammal. The method comprises topically administering to the skin or mucosal membrane an effective amount of a formulation comprising a) at least one microbicidal lipid, b) at least one solubilizing agent which keeps the lipid dissolved in the formulation, and optionally 3) a gel-forming agent. The formulation used in the method may suitable be in the form of a hydrogel. The microbicidal lipid is preferably a C.sub.6-18 fatty acid, such as, e.g., lauric acid, or a derivative thereof, e.g., a monoglyceride such as capric acid 1-monoglyceride. The solubilizing agent may suitably be a glycofurol such as the commercially-available glycofurol 75. The invention also relates to novel pharmaceutical formulations for use in the method. Excerpt(s): This application is a 371 of PCT/PK97/00524 filed Nov. 14, 1997. This invention relates to novel valuable uses of microbicidal lipids, in particular to a method for counteracting infection of the genital mucosa of a mammal by virus, pathogenic bacteria or fungi. The invention also relates to novel pharmaceutical formulations which may be used in the method as well as for other valuable uses such as for application to skin or non-genital mucosa. The World Health Organization (WHO) has estimated that as of late 1993 15 million adults and children world-wide were infected with HIV and that, in that year, heterosexual transmission accounted for up to 90% of new infections. It is projected that by the year 2000 the cumulative number of HIV infected individuals will reach 30 to 40 million people (Report of a meeting on the development of vaginal microbicides for the prevention of heterosexual transmission of HIV, WHO/GPA/RID/CRD/94.1, Geneva, Switzerland, 1993). Infections are on the rise in the developing countries, particularly in South and Southeast Asia, where the epidemic is to an increasing extent affecting young women of childbearing age. Also in the U.S. and other western societies, heterosexual transmission is causing an increasing proportion of AIDS cases (A. R. Lifson, Preventing HIV: have we lost our way? The Lancet 343, 1306-1307, 1994). These facts emphasise the need for effective means of protection against heterosexual transmission of HIV. Web site: http://www.delphion.com/details?pn=US06596763__
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Transfer and expression of gene sequences into nervous system cells using herpes simplex virus mutants with deletions in genes for viral replication Inventor(s): Breakefield; Xandra O. (Newton, MA), Martuza; Robert L. (Lexington, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,610,287 Date filed: December 27, 1994
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Abstract: This invention relates to methods of gene delivery to cells in the nervous system by introducing and expressing gene sequences mediated by herpes simplex virus 1 (HSV-1) vectors with a mutation in a gene for viral replication. The present invention further relates to methods for modulating neuronal physiology and for treating nervous system disorders. The present invention also relates to an animal model for nervous system disorders and to methods for producing such an animal model. Excerpt(s): This invention relates to methods of gene delivery into cells of the nervous system, for example, cells of the central and peripheral nervous system, by introducing and expressing gene sequences using herpes simplex virus 1 (HSV-1) mutants with deletions in gene(s) for viral replication. The delivery and expression of heterologous or native genes into cells of the nervous system to alter normal cellular biochemical and physiologic processes in a stable and controllable manner is of substantial value in the fields of medical and biological research. This genetic perturbation of the nervous system provides a means for studying the molecular aspects of neuronal function and offering therapeutic approaches to pathologic processes. Herpes simplex or other neurotropic viral vectors (Loewy et al., Proc. Soc. Neurosci. 17:603-15 (1991)) offer one potential means of delivering functional genes to alter the physiology of sensory or other neurons. Herpes simplex virus is known to be retrogradely transported from sensory terminals to sensory ganglia by a mechanism of fast axonal transport (Cook et al., Infec. and Immun. 7:272-288 (1973). HSV that reaches the nucleus of a sensory neuron, is capable of either lytic replication or latent infection. Lytic replication is characterized by the production of mature virus particles and destruction of the cell. Latent infection is characterized by the long-term stable presence of viral DNA in the nuclei of infected cells, most likely in the form of an episomal unit (Rock et al., Nature 302:523-525 (1983); Efstathiou et al., J. Virol 57(2):446-455 (1986); Mellerick et al., Virol 158:265-275 (1987)), and transcription that is limited to a specific region of the HSV genome (Croen et al., New Engl. J. Med. 317:1427-1432 (1987); Rock et al., J. Virol. 61:3820-3826 (1987); Spivak et al., J. Virol. 61:3841-3847 (1987); Stevens et al., Science 235:105-1059 (1987); Javier et al., Virol. 166:254-257 (1988); Wagner et al., J. Virol. 62(4):1194-1202 (1988); Kosz-Vnenchak et al., J. Virol. 64:5396-5402 (1990)). Web site: http://www.delphion.com/details?pn=US06610287__ •
Vaccine containing whole killed herpes viruses to prevent development of atherosclerotic plaque Inventor(s): Chaihorsky; Alexander (Garfield, NJ), Golubev; Daniel (New York, NY) Assignee(s): Bio-Virus Research Incorporated (San Matteo, CA) Patent Number: 6,471,965 Date filed: July 27, 1994 Abstract: A vaccine is disclosed for the prophylaxis against pathogenic development of atherosclerotic plaque in a mammalian subject susceptible thereto which consists essentially of a multiplicity of killed whole-virus strains, selected from the group consisting of:Herpes Simplex Virus 1;Herpes Simplex Virus 2;Herpes Simplex Virus 6;Human Cytomegalovirus; andEpstein-Barr Virus;in combination with a pharmaceutically acceptable inert vaccine carrier or diluent. Excerpt(s): This invention relates to a vaccine containing herpes virus for the prevention of atherosclerosis. More particularly the invention relates to a herpes vaccine containing
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several types of whole killed herpes viruses that affect humans and that acts as a prophylaxis against pathogenic development of atherosclerotic plaque in a mammalian subjected susceptible thereto. It is generally accepted that atherogenesis is triggered by primary injury to the endothelial lining of the arterial walls. This injury is believed to be the result of exposure of the underlying smooth muscle tells to several factors of noninfectious origin (hormones, low density lipoproteins, growth factors, among others). The prevailing view is that human atherosclerosis (AS) is a pleiotropic process with various causes. See Ross, R., The Pathogenesis of Atherosclerosis: An Update, New England J. Med.,314, 488 to 500 (1986). A fundamentally new etiological factor: herpes virus infection-was reported by Fabricant et al, who demonstrated that chickens infected with Marek Disease Virus (MDV), have an unusually high incidence of atherosclerotic plaque-(ASP) in the arteries. See Fabricant, C. G. et al, Virus-Induced Cholesterol Crystals, Science, 181, 566 to 567 (1973); and Fabricant, C. G. et al, Virus-Induced Atherosclerosis, J. Exp. Med., 148, 335 to 340 (1978). Since that time data have been accumulated suggesting the role of herpes virus in AS in humans. It was shown that different herpes viruses can alter smooth muscle cells lipid metabolism and induce cholesterol and cholesterol ester accumulation in these cells. See Fabricant, C. G. et al, Herpes Virus Infection Enhances Cholesterol and Cholesterol Ester Accumulation in Cultured Arterial Smooth Muscle Cells, Am. J. Pathol, 105, 176 to 184 (1981); Fabricant, C. G. et al, Herpes Virus-Induced Atherosclerosis in Chickens, Fed. Proc., 42, 2476 to 2479 (1983); Melnick, J. L. et al, Cytomegalovirus Antigen within Human Arterial Smooth Muscle Cells, Lancet, ii, 644 to 647 (1983); Gyorkey, F. et al, Herpesviridae in the Endothelial and Smooth Muscle Cells of Proximal Aorta in Atherosclerotic Patients, Exp. Mol. Pathol, 40, 328 to 339 (1984); Hajjar et al, Virus-Induced Atherosclerosis: Herpes Virus Infection Alters Aortic Cholesterol Metabolism and Accumulation, Am. J. Pathol., 122, 62 to 70 (1986); Adam et al, High Levels of Cytomegalovirus Antibody in Patients Requiring Vascular Surgery for Atherosclerosis, Lancet, 2, 291 to 293 (1987); Petrie, Association of Herpesvirus/Cytomegalovirus Infections with Human Atherosclerosis, Prog. Med. Virol., 35, 21 to 42 (1988); Grattan, M. T. et al, Cytomegalovirus Infection is Associated with Cardiac Allograft Rejection and Atherosclerosis, J. A. Med. Assoc., 261, 3561 to 3566 (1989); Mc Donald, K. et al, Association of Coronary Artery Disease in Cardiac Transplant Recipients with Cytomegalovirus Infection, Am. J. Cardiol., 64, 359 to 362 (1989); Visser et al, Granulocyte-Mediated Injury in Herpes Simplex VirusInfected Human Endothelium, Lab. Invest., 60, 296 to 304 (1989); Melnick, J. L. et al, Possible Role of Cytomegalovirus in Atherogenesis, J. Am. Assoc., 263, 2204 to 2207 (1990); Bruggeman, C. A. et al, The Possible Role of Cytomegalovirus in Atherogenesis, Prog. Med. Virol., 38, 1 to 26 (1991); Melnick, J. L. et al, Accelerated Graft Atherosclerosis Following Cardiac Transplantation; Do Viruses Play a Role?, Clin. Cardiol., 14 (Supp. II), 21 to 26 (1991); and Hajjar , D. P., Viral Pathogenesis of Atherosclerosis, Am. J. Pathol., 133, 1195 to 1211 (1991). Web site: http://www.delphion.com/details?pn=US06471965__
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Viral nucleotide sequences Inventor(s): Binns; Matthew McKinley (Huntingdon, GB), Griffin; Annette Mary (Huntingdon, GB), Ross; Louis Joseph Norman (Huntingdon, GB), Scott; Simon David (Huntingdon, GB) Assignee(s): Merial (Lyons, FR) Patent Number: 6,413,762 Date filed: December 26, 2000 Abstract: Various genes of herpes virus of turkeys (HVT) Marek's disease virus (MDV) and infectious laryngotracheitis virus (ILTV) have been identified as non-essential regions (and candidates for insertion sites for foreign genes) and/or as antigen-encoding regions. The former include the HVT homologue of the HSV (herpes simplex virus) gC gene, the TK (thymidine kinase) region of MDV or ILTV, ORF3 of ILTV (as defined herein), the ribonucleotide reductase (large subunit) gene of ILTV, MDV or HVT and the ribonucleotide reductase (small subunit) gene of MDV. The antigen-encoding regions include the HVT homologues of the HSV gB, gC and gH genes, the ILTV homologue of HSV gB, ORF2 of ILTV, and the HVT homologue of the HSV-1 immediate early genes IE-175 and IE-68. Manipulation of these genes allows vaccines to be prepared comprising attenuated virus or virus carrying heterologous antigen-encoding sequences. Excerpt(s): The present invention relates to viral nucleotide sequences which may be manipulated to provide vaccines against disease. Herpesviruses are large double stranded DNA viruses consisting of an icosahedral capsid surrounded by an envelope. The group has been classified as alpha, beta and gammaherpesviruses on the basis of genome structure and biological properties [Roizman, B et al (1981) Intervirology 16, 201-217]. Avian herpes viruses include Marek's Disease Virus (MDV) (a gammaherpesvirus) which causes a lymphomatous disease of considerable economic importance in chickens [reviewed in Payne, L. N. (ed) Marek's Disease (1985), Martinus Nijhoff Publishing, Boston] and Infectious Laryngotracheitis-Virus (ILTV) (an alphaherpesvirus) which causes an acute upper respiratory tract infection in chickens resulting in mortality and loss of egg production. A recent unexpected finding in out laboratory is that there is sufficient amino acid homology between MDV, ILTV and mammalian herpesviruses, particularly varicella zoster (VZV) and Herpes Simplex Virus (HSV) to allow identification of numerous conserved genes. These include the MDV and Herpesvirus of Turkeys (HVT) homologues of glycoproteins gB, gC and gH of HSV; the ILTV, MDV and HVT homologues of TK and ribonucleotide reductase genes and the ILTV homologue of gB and genes 34 and 35 of VZV (Buckmaster, A et al, (1988) J. gen. Viral, 69, 2033-2042. Web site: http://www.delphion.com/details?pn=US06413762__
Patent Applications on Herpes Simplex As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to herpes simplex: 10
This has been a common practice outside the United States prior to December 2000.
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Antimicrobial treatment for herpes simplex virus and other infectious diseases Inventor(s): Squires, Meryl J.; (Barrington Hills, IL) Correspondence: Thomas W. Tolpin; Welsh & Katz, LTD.; 22nd Floor; 120 South Riverside Plaza; Chicago; IL; 60606; US Patent Application Number: 20030099726 Date filed: March 7, 2002 Abstract: An improved medical treatment and medicine is provided to quickly and safely resolve herpes and other microbial infections. The inexpensive user-friendly medicine can be applied and maintained on the infected region until the physical symptoms of the disease disappears and the patient is comfortable and has a normal appearance. The attractive medicine comprises an antimicrobial concentrate comprising microbe inhibitors, phytochemicals or isolates. Desirably, the effective medicine comprises a surfactant and an aqueous carrier or solvent. In the preferred form, the medicine comprises Echinacea phytochemicals and benzalkonium chloride in a sterile water solution. Excerpt(s): The present invention relates to herpes virus, and more particularly, to medical treatments for herpes virus and other microbial infections. Herpes simplex virus (HSV) commonly referred to as "herpes virus" or "herpes," is an infectious disease which has reached crisis proportions nationally with estimated numbers of infected people at 70%-80% of our population as reported by the American Social Health Association (ASHA) and growing annually by 500,000 people or more. There are two common types of herpes: herpes simplex virus 1 (HSV 1) and herpes simplex virus 2 (HSV 2). Herpes enters the human body through minuscule breaks in the epidermal tissue usually by contact with an infected host and is marked by eruption of one or more vesicles, usually in groups, following an incubation period of approximately four to ten days. Typically the course of the infectious outbreak initiates with the prodromal stage; advancing to vesicular eruption; followed by: ulceration; coalescing; resolution; and the latency period. The outbreak can last for several weeks and on average lasts two-three weeks. In some immune compromised individuals the outbreak can last for months. The vesicles can appear anywhere on the skin or mucosa, typically appearing on the lips as cold sores, glands, oral mucosa, conjunctiva and cornea, genitalia, anal mucosa and perianal tissue. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combined vaccine compositions Inventor(s): Stephenne, Jean; (Rixensart, BE), Wettendorff, Martine Anne Cecile; (RhodeSaint-Genese, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030129199 Date filed: August 23, 2002 Abstract: Novel combined vaccine composition preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a V2V antigen, a
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HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3DMPL and QS21. Excerpt(s): This invention relates to novel vaccine formulations, methods for preparing them and their use in therapy. In particular the present invention relates to combination vaccines for administration to adolescents. HSV-2 is the primary etiological agent of herpes genitalis. HSV-2 and HSV-1 (the causative agent of herpes labialis) are characterised by their ability to induce both acute diseases and to establish a latent infection, primarily in neuronal ganglia cells. Genital herpes is estimated to occur in about 5 million people in the U.S.A. alone with 500,000 clinical cases recorded every year (primary and recurrent infection). Primary infection typically occurs after puberty and is characterised by the localised appearance of painful skin lesions, which persist for a period of between 2 to 3 weeks. Within the following six months after primary infection 50% of patients will experience a recurrence of the disease. About 25% of patients may experience between 10-15 recurrent episodes of the disease each year. In immunocompromised patients the incidence of high frequency recurrence is statistically higher than in the normal patient population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Complementing cell lines Inventor(s): Havenga, Menzo; (Alphen San Den Rijn, NL), Mehtali, Majid; (Plobsheim, FR), Vogels, Ronald; (Linschoten, NL) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030119192 Date filed: October 15, 2002 Abstract: A packaging cell line capable of complementing recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line is preferably derived from primary diploid human cells transformed by adenovirus E1 sequences either operatively linked on one or two DNA molecules, the sequences operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also, a cell line derived from PER.C6 that expresses functional Ad35E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter and terminated by a heterologous poly-adenylation signal. The new cell lines are useful for producing recombinant adenoviruses. The cell lines can be used to produce human recombinant therapeutic proteins such as human antibodies. In addition, the cell lines are useful for producing human viruses other than adenovirus such as influenza, herpes simplex, rotavirus, and measles. Excerpt(s): This application is a continuation of application Ser. No. 09/713,678, filed Nov. 15, 2000, pending (the contents of the entirety of which are incorporated by this reference), now U.S. Pat. No. ______, which is a continuation-in-part of application Ser. No. 09/573,740, filed May 18, 2000, pending, which claims benefit, under 35 U.S.C.sctn. 119(e), of the filing date of U.S. Provisional Application Serial No. 60/134,764, filed May 18, 1999. The invention relates to the field of biotechnology generally and, more specifically, to adenoviral-based complementing cell lines. Typically, vector and packaging cells are adapted to one another so that they have all the necessary elements, but they do not have overlapping elements which lead to replication-competent virus by recombination. Therefore, the sequences necessary for proper transcription of the
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packaging construct may be heterologous regulatory sequences derived from, for example, other human adenovirus ("Ad") serotypes, nonhuman adenoviruses, other viruses including, but not limited to, SV40, hepatitis B virus ("HBV"), Rous Sarcoma Virus ("RSV"), cytomegalovirus ("CMV"), etc. or from higher eukaryotes such as mammals. In general, these sequences include a promoter, enhancer and polyadenylation sequences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition and pharmaceutical preparation containing same for the treatment of herpes and related viral infections Inventor(s): Blay, Jonathan; (Bedford, CA), But, Paul P.H.; (N.T., HK), Foong, WaiChong; (Bedford, CA), Lee, Song F.; (Halifax, CA), Lee, Spencer H.S.; (Halifax, CA), Ooi, Vincent E.C.; (N.T., HK), Xu, Hong-Xi; (Halifax, CA), Zhang, Yongwen; (Shatin, CN) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030215529 Date filed: October 4, 2002 Abstract: In accordance with the present invention, novel compositions useful for the treatment of the cytopathogenic effects of an enveloped virus in mammals have been discovered by extraction and purification from the spikes of Prunella vulgaris. In particular, invention compositions comprise a lignin-carbohydrate complex as an active ingredient for inhibition of viral infection in a mammal. In accordance with an embodiment of the present invention, it has been discovered that invention compositions are effective agents for the prophylaxis and therapy in mammals of diseases caused by enveloped viruses, e.g., herpes simplex virus. Methods for producing invention compositions and uses therefor are also provided. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/160,210, filed Sep. 23, 1998, now pending, which claims priority from U.S. Provisional Application No. 60/059,775, filed Sep. 23, 1997, both incorporated by reference herein in their entirety. The present invention relates to a novel composition which can be extracted and purified from the spikes of Prunella vulgaris. Invention composition is an effective agent for treatment of the cytopathogenic effects of an enveloped virus in mammals. In another aspect, the present invention relates to methods for the treatment of the cytopathogenic effects of an enveloped virus and related indications in mammals, employing the invention composition as the active agent. In yet another aspect, the present invention relates to methods for the treatment of the cytopathogenic effects of an enveloped virus in mammals exposed to immunosuppressive regimens. In still another aspect, the present invention relates to methods for protecting mammals from reactivated viral infection during or following treatment with chemotherapeutic agents. In a further aspect, the present invention relates to methods for obtaining invention compositions having antiviral action from Prunella vulgaris, and formulations containing said compositions. In a still further aspect, the present invention relates to methods of purification of invention compositions from Prunella vulgaris and characterization thereof. In a particular aspect, the invention relates to compositions comprising lignin-carbohydrate complexes having anti-HSV activities. Viral infections caused by enveloped viruses are a heterogenous group of disorders characterized by viral infection of host cells. An example of such infections includes acquired herpes virus infections caused by broad categories of herpes-related viruses, including the alpha-, beta- and gamma-herpes viruses, and
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where the onset of infection is characterized by herpes simplex virus (HSV) infection of host cells. Primary herpes virus infections are normally acquired in childhood, but later enter a dormant phase (e.g., in the nerves). Reactivation of herpes virus infections result from a variety of factors, such as ultraviolet light, stress, and adult onset. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for the diagnosis and treatment of herpes simplex virus infection Inventor(s): Day, Craig H.; (Seattle, WA), Dillon, Davin C.; (Issaquah, WA), Hosken, Nancy A.; (Seattle, WA), McGowan, Patrick; (Seattle, WA), Sleath, Paul R.; (Seattle, WA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20020090610 Date filed: June 28, 2001 Abstract: Compounds and methods for the diagnosis and treatment of HSV infection are provided. The compounds comprise polypeptides that contain at least one antigenic portion of an HSV polypeptide and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits are also provided comprising such polypeptides and/or DNA sequences and a suitable detection reagent for the detection of HSV infection in patients and in biological samples. Excerpt(s): This application is related to U.S. Provisional Application No. 60/277,438 filed Mar. 20, 2001 and U.S. Provisional Application No. 60/215,458 filed Jun. 29, 2000 and are incorporated in their entirety by reference herein. The present invention relates generally to the detection and treatment of HSV infection. In particular, the invention relates to polypeptides comprising HSV antigens, DNA encoding HSV antigens, and the use of such compositions for the diagnosis and treatment of HSV infection. The herpes viruses include the herpes simplex viruses (HSV), comprising two closely related variants designated types 1 (HSV-1) and 2 (HSV-2). HSV is a prevalent cause of genital infection in humans, with an estimated annual incidence of 600,000 new cases and with 10 to 20 million individuals experiencing symptomatic chronic recurrent disease. The asymptomatic subclinical infection rate may be even higher. For example, using a typespecific serological assay, 35% of an unselected population of women attending a health maintenance organization clinic in Atlanta had antibodies to HSV type 2 (HSV-2). Although continuous administration of antiviral drugs such as acyclovir ameliorates the severity of acute HSV disease and reduces the frequency and duration of recurrent episodes, such chemotherapeutic intervention does not abort the establishment of latency nor does it alter the status of the latent virus. As a consequence, the recurrent disease pattern is rapidly reestablished upon cessation of drug treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Detection of herpes simplex virus Inventor(s): Espy, Mark J.; (Rochester, MN), Smith, Thomas F.; (Rochester, MN), Uhl, Jim; (Rochester, MN), Wold, Arlo; (Charles, MN) Correspondence: Mark S. Ellinger, PH.D.; Fish & Richardson P.C., P.A.; Suite 3300; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20020164586 Date filed: January 31, 2002 Abstract: The invention provides methods to detect herpes simplex virus (HSV) in biological samples and further to distinguish between HSV-1 and HSV-2. Primers and probes for the differential detection of HSV-1 and HSV-2 are provided by the invention. Articles of manufacture containing such primers and probes for detecting HSV are further provided by the invention. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) of U.S. provisional application serial No. 60/265,376, filed Jan. 31, 2001. This invention relates to viral diagnostics, and more particularly to detection of herpes simplex virus (HSV). Herpes simplex virus (HSV) is the virus most commonly detected in diagnostic laboratories, accounting for over 40% of the viruses that were detected in cell cultures over a 25-year period. HSV causes a variety of clinical syndromes, and anatomical sites infected include the skin, lips, oral cavity, eyes, genital tract, and central nervous system. Generalized or disseminated HSV infection may occur in patients immunologically compromised by neoplasia, organ transplantation, inherited immunodeficiency disease, or AIDS, or through neonatal infection acquired by transmission of the virus through an infected birth canal. Most disseminated disease is fatal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Eukaryotic gene expression cassette and uses thereof Inventor(s): Coffin, Robert S.; (London, GB), Latchman, David S.; (London, GB) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030219409 Date filed: January 31, 2003 Abstract: An expression cassette comprising a herpes simplex virus latency-associated transcript P2 region, a promoter and a heterologous gene operably linked in that order. The expression cassette is incorporated into herpes simplex virus vectors to allow for delivery of heterologous genes to mammalian cells for long-term expression. Excerpt(s): The present invention relates to a gene expression cassette. The expression cassette can be used for directing long-term expression of heterologous genes in eukaryotic cells. It also relates to the use of said expression cassette in gene therapy, vaccine production, and in methods of assaying for gene function. It further relates to vectors, including viral strains, comprising said expression cassette. Herpes simplex virus (HSV) has often been suggested as a suitable gene-delivery vector for the nervous system due to its neurotrophic lifestyle and its ability to remain latent in neurons for the lifetime of the cell. This unique ability has suggested that with suitable development a once-only application of such a vector system might give a lifelong therapeutic benefit for certain conditions, such as Parkinson's disease where expression of tyrosine
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hydroxylase or GDNF in the brain has been shown to be beneficial. However, while disabled herpes viruses have been shown efficiently to deliver genes to the nervous system and to other tissues in vivo, transcription of heterologous genes expressed from the herpes genome invariably only continues in the short term (<1 week). Transcription is shutoff as the herpes genome takes up the transcriptionally inactive state maintained during virus latency. Thus while herpes vector DNA probably remains in the treated cell for the lifetime of that cell, a therapeutic benefit would only be shown in the short term as the heterologous gene, while present, is usually not transcribed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Halovir, an antiviral marine natural product, and derivatives thereof Inventor(s): Fenical, William; (Del Mar, CA), Jensen, Paul R.; (San Diego, CA), Rowley, David C.; (Wakefield, RI) Correspondence: Brown, Martin, Haller & Mcclain Llp; 1660 Union Street; San Diego; CA; 92101-2926; US Patent Application Number: 20030013659 Date filed: August 9, 2002 Abstract: The invention is a group of compounds named halovirs with antiviral activity that are structurally related to compounds isolated from a marine fungus CNL240. Halovirs are comprised of a short, amphipathic helical peptide with an extended lipid moiety on the N-terminal end of the peptide. The halovirs have demonstrated activity against herpes simplex virus, types I and II. Excerpt(s): This application is a continuation in part of application Ser. No. 09/211,877 filed Dec. 15, 1998, of like title, which is incorporated herein by reference in its entirety. This invention relates generally to the field of pharmacologically active products derived from marine natural products. More specifically, it relates to peptides derived from a marine fungus that have antiviral activity. Viral infections have long been and continue to be a major cause of human suffering. The large variety of viruses combined with the diverse types of afflictions continue to challenge endeavors to find and make available agents capable of treating or mitigating the effects of viral infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Herpes simplex virus for treating unwanted hyperproliferative cell growth Inventor(s): Hermiston, Terry; (Corte Madera, CA), Laquerre, Sylvie; (Walnut Creek, CA) Correspondence: Gregory Giotta, PH.D.; Vice President And Chief Legal Counsel; Onyx Pharmaceuticals, INC.; 3031 Research Drive; Richmond; CA; 94806; US Patent Application Number: 20020072119 Date filed: December 8, 2000 Abstract: The present invention relates to pharmaceutical compositions, kits, and methods of use thereof, comprising, a mutant human herpes simplex-type 1 virus, which is cytopathic to susceptible hyperproliferative cells, such as neoplastic cells. Preferably, the virus does not produce a fully functionally active wild-type ICP0 polypeptide coded for the IE gene 1.
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Excerpt(s): From the early part of this century, viruses have been used to treat cancer. The approach has been two-fold; first, to isolate or generate oncolytic viruses that selectively replicate in and kill neoplastic cells, while sparing normal cells. Here investigators initially used wild type viruses, and this approach met with some, albeit, limited success. While oncolysis and slowing of tumor growth occurred with little or no damage to normal tissue, there was no significant alteration in the course of the disease. See, Smith et al., Cancer 9: 1211-1218 (1956), Cassel, W. A. et al., Cancer 18: 863-868 (1965), Webb, H. E. et al., Lancet 1: 1206-1209 (1966). See, also, Kenney, S and Pagano, J. J. Natl. Cancer Inst., vol. 86, no. 16, p.1185 (1994). More recently, and because of the reoccurrence of disease associated with the limited efficacy of the use of wild type viruses, investigators have resorted to using recombinant viruses that can be delivered at high doses, and that are replication competent in neoplastic but not normal cells. Such viruses are effective oncolytic agents in their own right, and further, can be engineered to carry and express a transgene that enhances the anti neoplastic activity of the virus. An example of this class of viruses is an adenovirus that is mutant in the E1B region of the viral genome. See, U.S. Pat. No. 5,677,178, and Bischoff, J. R., D. H. Kim, A. Williams, C. Heise, S. Horn, M. Muna, L. Ng, J. A. Nye, A. Sampson-Johannes, A. Fattaey, and F. McCormick. 1996, Science. 274:373-6. It is important to distinguish the use of replication competent viruses, with or without a transgene for treating cancer, from the second approach that investigators have used to treat cancer, which is a non-replicating virus that expresses a transgene. Here the virus is used merely as a vehicle that delivers a transgene which, directly or indirectly, is responsible for killing neoplastic cells. This approach has been, and continues to be the dominant approach of using viruses to treat cancer. It has, however, met with limited success, and it appears to be less efficacious than replicating viruses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Herpes simplex virus ICP4 is an inhibitor of apoptosis Inventor(s): Leopardi, Rosario; (Chicago, IL), Roizman, Bernard; (Chicago, IL) Correspondence: David L. Parker; Fulbright And Jaworski L.L.P.; 600 Congress Avenue, Suite 2400; Austin; TX; 78701; US Patent Application Number: 20020192822 Date filed: April 2, 2001 Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an a4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections. Excerpt(s): The present invention relates to the fields of molecular and cell biology generally, and more specifically, it addresses mechanisms for growth control in eurkaryotic cells. In particular, there are provided viral genes that inhibit normal cell death and methods for use thereof. The control of host cell gene expression, and often the control of genes involved in DNA replication, are integral parts of the life cycle of a virus. However, recent evidence suggests that most eukaryotic cells respond to viral disruption of normal cellular physiology by undergoing programmed cell death
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(apoptosis) (White, 1993). To counteract this, many viruses have evolved mechanisms to block host cell death (Clem and Miller, 1994; White and Gooding, 1994). In several cases, viral genomes have been found to contain genes whose products interact with proteins that play a central role in regulating cell survival. Programmed cell death is triggered by several factors and may take various forms. For example, the synthesis of doublestanded RNA activates kinases which phosphorylate the a subunit of eIF-2 and completely turn off protein synthesis (Sarrel, 1989). Ultimately, activation of metabolic pathways causes a pattern of morphological, biochemical, and molecular changes which result in cell death without spillage of cellular constituents which would result in an inflammatory response detrimental to the host (Wyllie, et al.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Herpes simplex virus strains Inventor(s): DeLuca, Neal A.; (Cheswick, PA) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030206888 Date filed: May 1, 2003 Abstract: The present invention provides an HSV having a genome with a mutation of a TAATGARAT sequence such that, in the presence of a ICP4 gene product, a native immediate early gene is expressed from the genome with delayed kinetics, the genome having a further inactivating mutation of each of the genes encoding ICP4. Excerpt(s): This patent application is a continuation of copending U.S. patent application Ser. No. 09/829,839, filed Apr. 10, 2001, which is a continuation of application Ser. No. 09/194,274, filed on Nov. 20, 1998, as a national phase of International Patent Application PCT/US97/08681, filed May 22, 1997, which is a continuation-in-part of application Ser. No. 08/651,419, filed on May 22, 1996, now U.S. Pat. No. 5,804,413. The present invention relates to herpes simplex virus strains, cell lines, methods for their production, and methods for their use. Herpes simplex virus (HSV) contains a doublestranded, linear DNA genome comprised of approximately 152 kb of nucleotide sequence, which encodes about 80 genes. The viral genes are transcribed by cellular RNA polymerase II and are temporally regulated, resulting in the transcription and subsequent synthesis of gene products in roughly discernible phases: Immediate Early (IE, or.alpha.), Early (E, or.beta.) and Late (L, or.gamma.). Immediately following the arrival of an HSV genome into the nucleus of an infected cell, the IE genes are transcribed. The IE genes are all activated by a complex including the HSV virion particle VP16 and the cellular factor, Oct-1, which binds to a consensus sequence (TAATGARAT) regulating IE gene expression (Preston et al., Cell, 52, 425-35 (1988)). The presence of this sequence, thus, confers the IE quality to HSV regulatory sequences. The efficient expression of IE genes, thus, does not require prior viral protein synthesis, while later expression depends upon the presence of IE gene products. The products of IE genes are required to activate transcription and regulate the remainder of the viral genome. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Herpes simplex virus type 1 ( HSV-1)-derived vector for selectively inhibiting maligant cells and methods for its use to treat cancer and to express desired traits in maligant and non-miligant mammalian cells Inventor(s): Black, Keith L.; (Los Angeles, CA), Nesburn, Anthony B.; (Malibu, CA), Perng, Guey-Chuen; (Alhambra, CA), Wechsler, Steven L.; (Westlake Village, CA), Yu, John S.; (Los Angeles, CA) Correspondence: Sidley Austin Brown & Wood; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20020098170 Date filed: November 29, 2001 Abstract: Disclosed is a method of selectively inhibiting the growth of malignant cells in mammals, including humans. The method selectively inhibits the growth of malignant cells of all varieties, and is particularly useful in treating brain tumors and other malignancies of the central nervous system. The method employs HSV-1-derived vectors containing a DNA having a deletion in both copies of the LAT gene and both copies of the ICP34.5 gene of HSV-1. The vectors are delivered to malignant cells either in vivo or in vitro, in accordance with the method. The HSV-1-derived expression vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid having a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-.gamma. A method of expressing in a mammalian cell a gene encoding a preselected protein, a method of treating a genetic defect, and a method of detecting an HSV-1 expressing cell also employ vectors of the present invention that contain at least one transcriptional unit of a constitutive LAT promoter operatively linked to and controlling the transcription of a gene encoding a preselected protein. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, useful for practicing the methods, and mammalian cells containing the HSV-derived vectors. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. The present invention is related to the medical arts, particularly to the field of gene therapy. Several animal models and animal types of malignant tumor have been used to study oncolysis with wild-type viruses. (Moore, Ann. Rev. Microbiol. 8: 393 [1954]; Moore, Progr. Exp. Tumor Res. 1: 411 [1960]). At least nine viruses have been shown to be capable of inducing some degree of tumor regression of a variety of tumors in animals. A major drawback found in these early studies, however, was systemic infection of the patient by the virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Herpes virus complementing cell line Inventor(s): Metcalfe, Karen; (Wilmington, MA) Correspondence: Leon R Yankwich; Yankwich & Associates; 201 Broadway; Cambridge; MA; 02139; US Patent Application Number: 20030049830 Date filed: October 10, 2002 Abstract: The present invention is directed to a cell line capable of supporting replication of a growth-defective Herpes Simplex Virus strain; specifically a replicationdefective HSV-2 double mutant. Particularly disclosed is a cell line that expresses the ICP8 protein and the UL5 protein of Herpes Simplex Virus. This cell line is useful to propagate a replication-defective HSV-2 vaccine strain that contains mutations and/or deletions in the ICP8 and UL5 genes. Excerpt(s): This application claims priority to U.S. provisional application No. 60/196,801, filed Apr. 13, 2000. The present invention is in the fields of cellular and molecular biology. Specifically, The present invention is directed to a cell line useful for the growth of a mutant strain of Herpesvirus. Herpesviridae is a large family of enveloped linear dsDNA-containing animal viruses. Herpesviruses are morphologically similar. The virion (.about.120-200 nm diam.) contains a core (DNA wound around a central protein structure) within an icosahedral capsid (.about.100-110 nm diam.) comprising 12 pentameric and 150 hexameric capsomers. The viron is enclosed by a lipoprotein envelope bearing surface projections. The linear dsDNA genome characteristically contains repeated terminal and/or internal sequences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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HSV viral vector Inventor(s): Ecob-Prince, Marion Suzanne; (Newcastle-Upon-Tyne, GB), Preston, Christopher Maurice; (Glasgow, GB) Correspondence: Alston & Bird Llp; Bank OF America Plaza; 101 South Tryon Street, Suite 4000; Charlotte; NC; 28280-4000; US Patent Application Number: 20030185855 Date filed: April 24, 2003 Abstract: The present invention relates to a recombinant herpes simplex virus (HSV) viral vector genome which has substantially lost its transducing properties as a result of a DNA sequence change in the gene coding for Vmw65 protein and also comprises an expressable heterologous gene inserted into a region of the HSV genome which is nonessential for the culture of the virus, the gene being under the control of the immediate early (IE1) gene enhancer of cytomegalovirus (CMV) and to the use of the recombinant HSV genome in therapy and vaccination. Excerpt(s): This application is a continuation of U.S. application Ser. No. 08/776,774, filed Jan. 28, 1997, which is a continuation of PCT/GB95/01787, international filing date Jul. 27, 1995, which are hereby incorporated in their entirety by reference. The present invention relates to a recombinant herpes simplex virus (HSV), especially type 1 (HSV1) or type 2 (HSV-2) having a good ability to continuously express an inserted heterologous gene whilst the virus is at the same time maintained in its latent nonreplicative state. A distinguishing feature of herpes virus infections is the ability to
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persist in the host for long periods in a non-replicative or latent state. Herpes simplex virus type 1 (HSV-1) establishes latent infection in human peripheral sensory ganglia and can reactivate to produce recurrent mucocutaneous lesions. Operationally, the pathogenesis of herpes virus infections can be divided into several distinct stages which can be studied individually in experimental animal models: acute viral replication, establishment of latency, maintenance, and reactivation. Following inoculation, HSV-1 replicates at the site of inoculation and is transported to sensory ganglia. Replication at the periphery or in sensory ganglia may increase the amount of virus that can establish latent infection. During latent infection, HSV-1 DNA can be detected in infected tissues but infectious virus cannot be detected. This latent state is often maintained for the life of the host. A variety of stimulae (such as fibrile illness and exposure to ultraviolet irradiation) can interrupt the latent state and cause the reappearance of infectious virus or reactivation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunologically significant herpes simplex virus antigens and methods for identifying and using same Inventor(s): Chen, Hongbo; (Shoreline, WA), Corey, Lawrence; (Mercer Island, WA), Fling, Steven P.; (Bainbridge Island, WA), Hosken, Nancy Ann; (Seattle, WA), Koelle, David M.; (Seattle, WA), McGowan, Patrick; (Seattle, WA), Posavad, Christine M.; (Seattle, WA) Correspondence: Attention OF Karen S. Canady; Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20020155122 Date filed: April 5, 2002 Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virallyencoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection. Excerpt(s): This application claims benefit of U.S. provisional patent applications No. 60/157,181, filed Sep. 30, 1999, No. 60/203,660, filed May 12, 2000, and No. 60/218,104, filed Jul. 13, 2000, the entire contents of each of which are incorporated herein by reference. Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention pertains. The invention relates to molecules, compositions and methods that can be used for the treatment and prevention of HSV infection. More particularly, the invention identifies epitopes of HSV proteins that can be used for the development of methods, molecules and compositions having the antigenic specificity of HSV-specific T cells, and in particular, of CD8+ T cells. Cellular immune responses are required to limit the severity of recurrent HSV infection in humans. Initial genital HSV-2 infections are prolonged and severe, while recurrences are less severe and more frequently asymptomatic. Resolution of primary HSV-2 infection is associated with infiltration of
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antigen-specific T cells, including CD8+ cytotoxic T lymphocytes (CTLs). Serial lesion biopsy studies of recurrent HSV-2 infection in humans has shown a shift to CD8+ predominance as lesions mature and correlation of local CTL activity with virus clearance (Koelle, D M et al., J. Clin. Invest. 1998, 101:1500-1508; Cunningham, A L et al., J. Clin. Invest. 1985, 75:226-233). Thus, HSV antigens recognized by CD8+ CTL can be used for novel therapies and vaccines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors Inventor(s): Brady, Roscoe O.; (Rockville, MD), Lai, Zhennan; (N. Potomac, MD), Reiser, Jakob; (New Orleans, LA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030119770 Date filed: August 2, 2002 Abstract: The present invention is related to use of recombinant lentiviral vectors containing a therapeutic gene of interest fused in-frame with an intercellular trafficking gene for the global delivery of therapeutic proteins in nondividing cells. Excerpt(s): This application claims the benefit of priority of U.S. provisional patent application No. 60/310,012, filed Aug. 2, 2001, which is hereby expressly incorporated by reference in its entirety. A number of obstacles currently limit the effectiveness of gene therapy. One of the most formidable is the delivery of desired genes or proteins to a sufficient number of target cells to elicit a therapeutic response. Recently, a series of virus-encoded and other regulatory proteins were found to possess the ability to cross biological membranes. For example, peptides derived from the Drosophila Antennapedia homeodomain are internalized by cells in culture (Derossi, D. et al. 1994 J Biol Chem 269:10444-10450; Derossi, D. et al. 1996 J Biol Chem 271:18188-18193) and conveyed to cell nuclei where they can directly and specifically interfere with transcription (Derossi, D. et al. 1996 J Biol Chem 271:18188-18193; Le Roux, I. et al 1995 FEBS Lett 368:311-314). The HIV-1 Tat protein was reported to enhance intercellular trafficking in vitro (Frankel, A. D. & Pabo, C. O. 1988 Cell 55:1189-1193; Green, M. & Loewenstein, P. M. 1988 Cell 55:1179-1188). The Tat protein is composed of 86 amino acids and contains a highly basic region and a cysteine-rich region (Frankel, A. D. & Pabo, C. O. 1988 Cell 55:1189-1193). It was found that Tat-derived peptides as short as 11 amino acids are sufficient for transduction of proteins (Fawell, S. et al. 1994 PNAS USA 91:664-668; Nagahara, H. et al. 1998 Nat Med 4: 1449-1452). However, the exact mechanism by which the 11-amino acid transduction domain crosses lipid bilayers is poorly understood. Schwarze et al. (Schwarze, R. S. et al. 1999 Science 385:1569-1572) have recently generated a Tat-galactosidase fusion protein that was delivered efficiently into brain tissue and skeletal muscle in vivo. These findings suggest that protein therapies may be successfully developed provided that problems caused by immune response and toxicity that might be associated with long-term expression of novel proteins in vivo can be solved. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Ligand capture-directed selection of antibody Inventor(s): Burioni, Roberto; (Del Mar, CA), Burton, Dennis R.; (La Jolla, CA), Sanna, Pietro P.; (San Diego, CA), Williamson, R. Anthony; (Del Mar, CA) Correspondence: Fish & Richardson P.C.; Suite 500; 4350 LA Jolla Village Drive; San Diego; CA; 92122; US Patent Application Number: 20020168629 Date filed: February 19, 2002 Abstract: The present invention provides a novel method for the identification and clonal isolation of antibodies that bind to unique epitopes. The method is based on the use of antibodies as solid phase capture reagents to bind a known capture antibody epitope, thereby precluding the capture antibody epitope from being presented to a population of antibodies to be screened. The method is particularly suited for screening libraries of cloned antibodies, such as phage display combinatorial antibodies. An antibody specific for herpes simplex virus (HSV), was employed as a model for the assay. Excerpt(s): The present invention relates generally to immunological assay techniques and specifically to a method for identifying an antibody that binds to a novel epitope through the use of solid-phase capture reagents that bind antigen at a preselected epitope and panning of a combinatorial library. Generally, any preparation of polyclonal or monoclonal antibodies can be used as a source of antibody molecules for cloning purposes. The use of filamentous phage display vectors, referred to as phagemids, has been repeatedly shown to allow the efficient preparation of large libraries of monoclonal antibodies having diverse and novel immuno-specificities. The technology uses a filamentous phage coat protein membrane anchor domain as a means for linking geneproduct and gene during the assembly of filamentous phage replication, and has been used for the cloning and expression of antibodies from combinatorial libraries (Kang, et al, Proc. Natl. Acad. Sci., U.S.A., 88:4363, 1991). Combinatorial libraries of antibodies have been produced using both the cpVIII membrane anchor and the cpIII membrane anchor (Barbas, et al., Proc. Natl. Acad. Sci., U.S.A., 88:7978, 1991). The diversity of a phagemid library can be manipulated to increase and/or alter the immunospecificities of the monoclonal antibodies of the library to produce and subsequently identify additional, desirable, human monoclonal antibodies. For example, the heavy (H) chain and light (L) chain immunoglobulin molecule encoding genes can be randomly mixed (shuffled) to create new HL pairs in an assembled immunoglobulin molecule. Additionally, either or both the H and L chain encoding genes can be mutagenized in a complementarity determining region (CDR) of the variable region of the immunoglobulin polypeptide, and subsequently screened for desirable immunoreaction and neutralization capabilities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Ligand for herpes simplex virus entry mediator and methods of use Inventor(s): Ware, Carl; (Solana Beach, CA) Correspondence: Robert M. Bedgood; Pillsbury Winthrop Llp; 50 Fremont Street; San Francisco; CA; 94120; US Patent Application Number: 20030060605 Date filed: September 28, 2001
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Abstract: A novel polypeptide ligand, p30, or LIGHT, for herpes virus entry mediator, HVEM, is provided. LIGHT is useful for modulating immune responses and in inhibiting infection and/or subsequent proliferation by herpesvirus. HVEM fusion proteins are also provided. Methods for treating subjects with lymphoid cell disorders, tumors, autoimmune diseases, inflammatory disorders or those having or suspected of having a herpesvirus infection, utilizing p30 and the fusion proteins of the invention, are also provided. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/549,096, filed Apr. 12, 2000, which is a continuation-in-part of U.S. Ser. No. 08/898,234, filed Jul. 30, 1997 (now U.S. pat. No. 6,140,467), which claims priority to U.S. Ser. No. 60/051,964, filed Jul. 7, 1997, and which are incorporated herein by reference in their entirety for all purposes. The invention relates generally to compounds and methods useful in regulating immune responses and viral infection. Herpes simplex virus (HSV), types 1 and 2, causes recurrent infections that range in severity from benign to serious. HSV emerges from latency in neurons to infect the skin and other tissues in the presence of a competent cellular immune system. The D glycoprotein (gD) of HSV, a transmembrane protein located in the virion envelope, initiates infection by binding to cellular receptors (Spear et al. (1993) Viral Fusion Mechanisms. Ed. Bentz. CRC press, Boca Raton). Recently, a cellular protein used by HSV for infection was identified and given the term HSV entry mediator (HVEM) (Montgomery (1996) Cell 87:427). HVEM is a transmembrane type 1 protein with a cysteine-rich extracellular domain that exhibits significant homology with receptors for tumor necrosis factor (TNF)-related cytokines (Smith et al. (1994) Cell 76:959; Ware et al. (1995) in, Pathways of Cytolysis. Eds. Griffiths and Tschopp. Springer-Verlag, Basel). Many of the TNF superfamily members initiate a variety of cellular responses necessary to mount effective inflammatory and immune responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Means of inducing durable immune responses Inventor(s): Brockman, Mark; (Boston, MA), Knipe, David; (Auburndale, MA) Correspondence: Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030215463 Date filed: March 24, 2003 Abstract: A replication defective herpes virus vector is described. The replication defective herpes virus vector has a deletion of at least a fragment of a U.sub.L29 gene that is replaced with a heterologous sequence encoding an antigen from a specific infectious disease agent. The vector can express said antigen. Prior HSV infection did not diminish the magnitude or the durability of the IgG antibody response generated by preferred replication-defective HSV-1 vectors. A method of inducing in a mammal an immune response against a specific infectious disease agent also is described. A recombinant replication defective mutant Herpes Simplex Virus as a vaccine is administered to a mammal to elicit in the mammal an immune response against the infectious disease causing agent. Excerpt(s): The present application claims the benefit of U.S. provisional application No. 60/366,977 filed Mar. 22, 2002, and which is incorporated herein by reference in its entirety. This invention relates to the construction of vectors that produce a durable protective immune response and may be used repeatedly and still obtain a strong
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immune response, regardless of prior host immunity. Herpes Simplex Virus (HSV) infection often results in a localized lesion within epithelial cells of the skin or a mucosal membrane. The innate immune response, consisting of macrophages, natural killer (NK) cells, cytokines, and complement proteins, may act to contain initial viral infection. NK cell-mediated lysis and numerous cytokines, including interleukin (IL)-12, IL-18, and gamma interferon and tumor necrosis factor-alpha, have been reported to affect HSV pathogenesis in mouse models of disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and composition for treating viral outbreaks Inventor(s): Dolak, Terence M.; (Andover, NJ) Correspondence: Gibbons, Del Deo, Dolan, Griffinger & Vecchione; 1 Riverfront Plaza; Newark; NJ; 07102-5497; US Patent Application Number: 20030152640 Date filed: March 10, 2003 Abstract: The invention provides a method and composition for treatment of lesions associated with viral infections, such as human Herpes simplex, by applying to the lesions an effective amount of a topical composition comprising: propolis extract in from about 0.5 to 10%, preferably about 1 to 8%, by weight; a skin protectant in from about 0.5% to 50% by weight; a penetration enhancing agent in from about 5 to 30%, preferably 5 to 25%, by weight; and an emulsifier in from about 1 to 20% by weight. The subject compositions possess enhanced activity in the treatment of such lesions in that they stop the outbreak at the stage of progression when they are applied and promote full healing, generally within 36 to 48 hours. Excerpt(s): This application is a continuation-in-part of copending U.S. patent application Ser. No. 10/151,347, filed May 20, 2002, which in turn is a continuation-inpart of U.S. patent application Ser. No. 09/952,119, filed Sep. 14, 2001, now abandoned. This invention relates to a method and composition for the treatment of lesions associated with viral infections, such as Herpes simplex or Herpes zoster. Herpes viral infections are chronic. Once the virus enters the body, it lies dormant in the nerve cells and periodically reactivates. When the virus reactivates, it characteristically causes a sore at the site where it first entered the body. To date, there is neither a vaccine to prevent the Herpes infection, nor any way to eliminate the virus from the body. Once infected, the patient has the virus for life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for the diagnosis and treatment of viral disease using 55092 Inventor(s): Cook, W. James; (Hanover, NH), Meyers, Rachel; (Newton, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20020146686 Date filed: December 6, 2001 Abstract: The present invention relates to methods and compositions for the diagnosis and treatment of viral disease, including, but not limited to, herpes simplex virus,
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hepatitis B and hepatitis C viral infection. Specifically, the present invention identifies PLD 55092 genes which are differentially expressed in virus infected cells, relative to their expression in normal, uninfected cells. The present invention describes methods for the diagnostic evaluation and prognosis of various viral diseases, and for the identification of subjects exhibiting a predisposition to such conditions. The present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of viral disease, and for monitoring the efficacy of compounds in clinical trials. The present invention also provides methods for the identification and therapeutic use of compounds as treatments of viral disease. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/254,037, filed Dec. 7, 2000, the entire contents of which are incorporated herein by this reference. Phospholipases are involved in the signal transduction pathway in which a cell response such as proliferation or secretion is produced in response to an extracellular stimulus. The interaction of extracellular signals (e.g., hormones, growth factors, cytokines, neurotransmitters, and physical stimuli) with cell surface receptors (e.g., G protein-coupled receptors and receptor tyrosine kinases) often activates a phospholipase D (PLD)-mediated signal transduction pathway that is important in the regulation of cell function and cell fate. Phospholipase D catalyzes the hydrolysis of phosphatidylcholine and other phospholipids yielding phosphatidic acid and is, thus, able to modify various lipid constituents of the plasma membrane and generate intracellular messengers that act to recruit and/or modulate specific target proteins. For example, addition of short chain analogues of phosphatidic acid to intact cells has been shown to regulate membrane transport, e.g., secretion of viral glycoproteins and matrix metalloproteinase proteins (Bi, K et al. (1997) Curr. Biol. 7:301-7; Williger, B T et al. (1999) J. Biol. Chem. 74:735-8). Moreover, phosphatidic acid is further metabolized to form diacylglycerol, a potent activator of protein kinase C, and lysophosphatidic acid (Exton, J H (2000) Ann. N Y Acad. Sci.905:61-8; Ktistakis N T et al. (1999) Biochem. Soc. Trans. 27:634-637). PLD is also able to catalyze a transesterification reaction (transphosphatidylation) utilizing short-chain primary alcohols as phosphatidyl group acceptors and producing phosphatidylalcohols. PLD activity is regulated by factors such as small GTP binding proteins of the ADP-ribosylation factor (ARF) and Rho families, and protein kinase C. PLD activities have been identified in multiple cellular membranes including the nuclear envelope, endoplasmic reticulum, Golgi apparatus, transport/secretory vesicles, and the plasma membrane (Ktistakis N T et al. (1999) Biochem. Soc. Trans. 27:634-637). Different PLD isoforms are localized in distinct cellular organelles, and serve diverse functions in signal transduction, membrane homeostasis, membrane vesicle trafficking and cytoskeletal dynamics (Singer W D et al. (1997) Ann. Rev. Biochem. 66:475-509; Exton, J H (2000) Ann. N Y Acad. Sci.905:61-8). The phospholipase D gene superfamily, as defined by structural domains and sequence motifs, includes PLDs, phosphatidyltransferases, phospholipid synthases, phosphodiesterases, endonucleases, and viral envelope proteins (Cao, J -X et al. (1997) Virus Research 48:11-18; Pedersen K M et al. (1998) J. Biol. Chem. 273:31494-31504; Barcena J (2000) J. Gen. Virol. 81:1073-1085; Liscovitch, M et al. (2000) Biochem. J. 345:401-415). PLD superfamily members share conserved motifs, including the HKD motif (HXKX.sub.4D) (SEQ ID NO:4) which has been implicated in catalytic activity (Ponting C P et al. (1996) Protein Science 5:914-922; Koonin, E V (1996) TIBS 21:242-243; Sung T -C et al. (1997) EMBO J. 16:4519-4530). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for preventing lesions caused by viruses of the herpesviridae or poxviridae family Inventor(s): Konowalchuk, Jack; (Newport, OR), Konowalchuk, Thomas W.; (Newport, OR) Correspondence: Steven C. Petersen; Hogan & Hartson, Llp; Suite 1500; 1200 17th Street; Denver; CO; 80202; US Patent Application Number: 20020165279 Date filed: December 6, 2001 Abstract: A method for preventing lesions caused by a virus of the Herpesviridae or Poxviridae family, comprising topically applying a composition consisting essentially of a C1 to C3 monohydroxy alcohol or a C2 to C4 diol and a sufficient amount of an acid to adjust the pH of the composition to below 4.6. Topical administration of the composition is preferred and is effective in treating lesions associated infections by viruses such as herpes simplex. Pharmaceutical compositions for use in the present method are provided. Excerpt(s): The present invention relates to virucidal compositions for the treatment and/or prevention of superficial lesions or sores, including canker sores and lesions caused by viruses of the Herpesviridae and Poxviridae families. Pathogenic viruses can be classified into two general types with respect to the viral structure, i.e., those that contain lipids and those that do not. Some well known lipid-containing pathogenic viruses, known as "enveloped" viruses, include herpes virus, e.g., herpes simplex 1 and 2; myxovirus, e.g., influenza virus; paramyxovirus, e.g., virus responsible for measles and mumps, and respiratory syncitial virus responsible for croup; corona virus, which is also implicated in the common cold; and toga virus, e.g., rubella virus and virus responsible for encephalitis and hemorrhagic fever. Many other pathogenic viruses lack an outer envelope, and therefore are characterized as "naked" viruses. Included in this category are the rhinovirus (the principle causative agent of the "common cold"), influenza viruses, polioviruses, and adenoviruses. Viral infections cause considerable discomfort, disease and can be fatal. Viruses such as cytomegalovirus (CMV), human lymphotrophic viruses (e.g., HTLV-1) and human immunodeficiency viruses (e.g., HIV1) result in significant morbidity and mortality. Herpes simplex viruses (HSV-1 and HSV-2) are associated with inflammation and lesions of the skin and mucosal membranes, including cold sores, fever blisters and genital herpes lesions. Varicellazoster virus (VZV) causes chicken pox and shingles, and Epstein-Barr virus (EBV) is associated with mononucleosis. Influenza viruses cause flu symptoms and can be fatal. HIV causes acquired immunodeficiency, which debilitates and kills infected individuals. Although these viruses may remain latent in some cells and for varying periods of time, generally viral replication results in irreversible destruction of the infected cell producing different clinical manifestations of the diseases they cause. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treating subjects infected with a herpes virus or neisseria gonorrheae Inventor(s): Docherty, John; (Kent, OH), Tsai, Chun-che; (Kent, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20020103262 Date filed: August 15, 2001 Abstract: The present invention provides a method of inhibiting the formation of infectious herpes virus particles, particularly infectious herpes simplex virus (HSV) particles, in a host cell. The method involves administering an effective amount of a hydroxylated tolan, particularly a polyhydroxylated tolan, to a herpes virus infected host cell. The present invention also provides a method of treating a herpes virus infection, particularly an HSV infection. The method comprises administering a topical composition comprising a therapeutically effective amount of a hydroxylated tolan to a herpes virus-infected site. The present invention also relates to a topical composition for treating a herpes virus infection selected from the group consisting of an HSV infection, a cytomegalovirus infection, and a varicella zoster virus infection. The present invention also provides a method of treating a subject infected with Neisseria gonorrhea. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/225,609, filed Aug. 15, 2000. The present invention relates to compositions which inhibit replication of herpes virus and the bacterium Neisseria gonorrheae, and methods of using such compositions to treat subjects infected with these microorganisms. Human herpes viruses can infect host cells in virtually any organ of the human body. Replication of a herpes virus within an infected host cell leads to lysis of the infected cell and the release of large numbers of infectious virus. The infectious particles released from the lysed cell can infect and destroy other cells at or near the site of the initial infection. These infectious particles can also be transmitted to a non-infected individual. Human herpes viruses can also enter and remain latent, i.e., in the non-replicative state, in other cells of the afflicted individual for life. This life-long infection serves as a reservoir of infectious virus for recurrent infections in the afflicted individual and as a source of infection for an unwitting contact. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mutated herpes simplex virus type 1 thymidine kinases and uses thereof Inventor(s): Compadre, Cesar; (Little Rock, AR), Drake, Richard; (Little Rock, AR), Hinds, Trenton; (US), Hurlburt, Barry; (Little Rock, AR), Rechtin, Tammy; (Birmingham, AL) Correspondence: DR. Benjamin Adler; Adler & Associates; 8011 Candle Lane; Houston; TX; 77071; US Patent Application Number: 20020146796 Date filed: June 8, 2001 Abstract: The present invention provides new site-specific HSV-thymidine kinase mutants with improved nucleoside analog metabolizing activity due to low or no thymidine phosphorylation ability. Also provided is a method of killing target cells using such mutants combined with a prodrug.
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Excerpt(s): This patent application claims benefit of provisional patent application U.S. Serial No. 60/090,271, filed Jun. 22, 1998, now abandoned. The present invention relates generally to the field of molecular biology of herpes simplex viruses and vaccine technology. More specifically, the present invention relates to a means of improving gene therapy for diseases such as cancer by mutating herpes simplex virus type 1 thymidine kinases and uses thereof. The herpes simplex virus thymidine kinases (HSVTKs).sup.1 are the pharmacological targets of most herpesvirus treatments (1, 2), and more recently, HSV-1 TK has been utilized as a suicide gene therapeutic for cancer in combination with ganciclovir (3, 4). The basis for these uses is their ability to specifically phosphorylate anti-herpesvirus nucleoside drugs such as acyclovir (ACV), ganciclovir (GCV) and 5-bromovinyldeoxyuridine (BVDU) (1, 2, 5). This targeting is based primarily on the differences in substrate specificity compared to the cellular TKs. The HSV-1 TK has a much broader range of substrates which include most pyrimidine nucleosides, many guanosine derivatives (e.g., ACV or GCV), and most purine and pyrimidine nucleoside triphosphates (6-9). HSV-TK also possesses a thymidylate kinase (TMPK) activity, but this activity is restricted to only deoxypyrimidine monophosphate substrates (7-9). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Neuronal cell model and methods of use thereof Inventor(s): Danaher, Robert J.; (Lexington, KY), Jacob, Robert J.; (Lexington, KY), Miller, Craig S.; (Nichlasville, KY) Correspondence: Mcdermott, Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20030032006 Date filed: October 29, 2001 Abstract: We previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally-differentiated (ND)-PC12 cells that allows for inducible virus replication upon forskolin and heat stress (HS) treatment. In this research, we further characterized the model with respect to HSV-2 strain 333. We found that: (i) ND-PC12 cells are non-permissive to HSV-2 replication; (ii) HSV-2 can establish a quiescent infection, like HSV-1, in ND-PC 12 cells with the transient use of acycloguanosine (ACV); however unlike HSV-1, anti-viral conditions are not obligatory to establish and maintain a quiescent state; (iii) the quiescent state is maintained in the presence of Vero cell cocultivation indicating that such cultures are free of infectious virus; and (iv) a high percentage of quiescently infected (QIF)-PC 12 cell cultures (80100%) produce HSV-2 in response to forskolin and HS (43.degree. C., 3 h) treatment for as long as 4 weeks post infection. These findings indicate that ND-PC12 cells can harbor HSV-2 in a cryptic and non-productive state that is reversible. This model has appealing features for studying gene expression during the establishment, maintenance and reactivation phases of the HSV-2 quiescent state in cell culture. Journal of Neuro Virology (2000) 6, 296-302. Excerpt(s): The present application claims the benefit of priority to U.S. Provisional Application No. 60/243,701, filed Oct. 27, 2000. The contents of this provisional application are incorporated herein by reference in its entirety. The present invention relates, in general, to neurally-differentiated cells infected with viruses in a manner that supports a long-term non-productive infection for experimentation concerning the reactivation, induction, suppressing of virus latency. Herpes simplex virus types 1 and 2
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(HSV-1 and -2) are alphaherpesviruses with similar, but unique molecular (Kieff et. al., 1971, 1972), biological and clinical features (reviewed in Whitley, 1996). The genomes are approximately 150 kb in size and each contains corresponding sets of 74 genes (Dolan et al, 1998). Both viruses infect epithelium, with HSV-1 having a predilection for orofacial sites and HSV-2 preferentially infecting genital surfaces. During the primary infection, HSV invades local nerve endings and travels to sensory ganglia where it can colonize neuronal nuclei and establish a latent state (Hill et al, 1972, Stevens and Cook, 1971). Reactivation of HSV from latency occurs intermittently as a result of stressful stimuli (e.g., trauma and heat). Reactivated viruses are responsible for causing recurrent epithelial infections that can occur in up to 89% of infected individuals (Benedetti, et. al. 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Peptide epitope-based vaccine for treating herpes simplex virus infections and related diseases Inventor(s): BenMohamed, Lbachir; (Arcadia, CA), Nesburn, Anthony B.; (Malibu, CA) Correspondence: Richard H. Zaitlen; Pillsbury Winthrop Llp; Suite 2800; 725 South Figueroa Street; Los Angeles; CA; 90017-5406; US Patent Application Number: 20030219448 Date filed: August 6, 2002 Abstract: Described herein are peptide epitopes effective in the treatment of herpes simplex virus (HSV), as well as vaccines and other therapeutic compositions including the same. In various embodiments, the compositions of the present invention may include a pharmaceutically acceptable adjuvant to enhance the delivery and/or pharmacological efficacy of the epitope. Also described are methods for treating and preventing HSV with the aforementioned epitopes, such as by administering a vaccine including the same. Other methods describe the use of the TEPITOPE algorithm to identify epitopes that may be useful in the treatment of HSV and related or unrelated disease conditions. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn. 119(e) of U.S. provisional application serial No. 60/383,170, filed May 24, 2002, the contents of which are hereby incorporated by reference in their entirety. Embodiments of the present invention are directed to a composition and methods for treating and preventing Herpes Simplex Virus infection, based upon peptide epitopes. The incidence of Herpes Simplex Virus (HSV) has risen 30 percent since the 1970's. One in four adults has HSV, and there are an estimated one million new cases of this disease every year. HSV infections have been associated with a spectrum of clinical syndromes including cold sores, genital lesions, corneal blindness and encephalitis. The percentage of infected persons who are not cognizant of their own infection with HSV is over 50% largely because these individuals either do not express the classic symptoms (e.g., they remain asymptomatic) or because they dismiss HSV as merely an annoying itch or rash in those cases in which the disease has external manifestations. Additionally, HSV may be treated, but clinical research has yet to identify a cure. Therefore, one cannot rid himself of HSV once infected; one can merely attempt to control infection when it reactivates. However, despite the increase of HSV prevalence during the last three decades, an effective vaccine that could help to control this epidemic is still not available. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides for inhibition of herpes simplex virus entry Inventor(s): Cohen, Gary H.; (Havertown, PA), Eisenberg, Roselyn J.; (Haddonfield, NJ), Lambris, John D.; (Bryn Mawr, PA), Montgomery, Rebecca I.; (Lodi, WI), Sarrias, Maria Rosa; (Barcelona, ES), Spear, Patricia G.; (Chicago, IL) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20020119165 Date filed: February 16, 2001 Abstract: The invention includes antiherpesviral peptides and method of generating the same. Excerpt(s): The field of the invention is inhibition of virus entry into cells. Herpes Simplex Virus (HSV) entry into mammalian cells is a complex process requiring interaction of multiple viral envelope proteins with several host cell membrane receptors. Virion glycoproteins, including gB and gC, appear to mediate initial virus binding to cell surface heparan sulfate glycosaminoglycans. However, this attachment is not sufficient to mediate entry, since some cell types such as swine testis (ST) or Chinese hamster ovary (CHO) cells bind HSV but are not susceptible to infection. Entry of virus into cells requires binding of yet other glycoprotein(s) to one or more cell surface receptors. Glycoproteins gD, gB, and the complex formed by gH and gL are believed to act separately or in concert to promote pH-independent fusion of the viral envelope with the cellular membrane. Herpesvirus entry mediator protein, a cellular protein designated as HveA (also designated HVEM in some literature sources), is a member of the tumor necrosis factor receptor (TNFR) superfamily. This protein has been described as a target cellular receptor capable of mediating post-attachment entry of HSV into host cells. HveA was identified by expression cloning of several HeLa cell products which, when expressed in otherwise nonpermissive CHO cells rendered the CHO cells susceptible to entry by many HSV strains. A recombinant form of HveA (HveA:Fc) blocked HSV-1 entry into CHO cells which were stably transformed to express HveA. Additionally, antibodies to HveA inhibited HSV-1 entry into some susceptible cell types. Furthermore, a recent study suggests that HveA participates not only in entry of free virus into cells but also in cell-to-cell spread of infection. These studies suggest that HveA mediates virus entry into mammalian cells (Terry-Allison et al., 1998, J. Virol. 72:5802-5810; Montgomery et al., 1996, Cell 87:427-436). The HSV protein which mediates HSV binding with HveA has been shown to be glycoprotein D (gD), which binds with a soluble form of HveA, designated HveA(200t) (Whitbeck et al., 1997, J. Virol. 71:6083-6093) in a specific and saturable manner and inhibits binding of HSV to HveA-expressing cells (Nicola et al., 1997. J. Virol. 71:2940-2946; Nicola et al., 1996, J. Virol. 70:3815-3822; Sodora et al., 1991, J. Virol. 63:5184-5193; Sodora et al., 1991, J. Virol. 65:4424-4431; Tal-Singer et al., 1994, Virology 202:1050-1053; Whitbeck et al., 1997, J. Virol. 71:6083-6093). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 237
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Polynucleotide herpes virus vaccine Inventor(s): Armstrong, Marcy E.; (Schwenksville, PA), Keys, Robert D.; (Norristown, PA), Lewis, John A.; (Norristown, PA), Liu, Margaret A.; (Rosemont, PA), McClements, William L.; (Doylestown, PA) Correspondence: Merck & CO., INC.; Patent Department; P.O. Box 2000 - Ry60-30; Rahway; NJ; 07065-0907; US Patent Application Number: 20020147167 Date filed: April 16, 2001 Abstract: Genes encoding herpes simplex virus type 2 (HSV-2) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. In a DNA titration, it was found that a single immunization of.gtoreq.0.5.mu.g of (one) PNV, gave >90% seroconversion by ten weeks post immunization. Immune antisera neutralized both HSV-2 and HSV-1 in cell culture. When animals were challenged with HSV-2, significant (p<0.001) protection from lethal infection was achieved following PNV vaccination. DNA constructs may be full-length, truncated and/or mutated forms and may be delivered along or in combination in order to optimize immunization and protection from HSV infection. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. (not yet known), filed Sep. 18, 1996, which is a continuation application of U.S. application Ser. No. 08/279,459, filed Jul. 22, 1994. A major obstacle to the development of vaccines against viruses, particularly those with multiple serotypes or a high rate of mutation, against which elicitation of neutralizing and protective immune responses is desirable, is the diversity of the viral external proteins among different viral isolates or strains. Since cytotoxic T-lymphocytes (CTLs) in both mice and humans are capable of recognizing epitopes derived from conserved internal viral proteins [J. W. Yewdell et al., Proc. Natl. Acad. Sci. (USA) 82, 1785 (1985); A. R. M. Townsend, et al., Cell 44, 959 (1986); A. J. McMichael et al., J. Gen. Virol. 67, 719 (1986); J. Bastin et al., J. Exp. Med. 165, 1508 (1987); A. R. M. Townsend and H. Bodmer, Annu. Rev. Immunol. 7, 601 (1989)], and are thought to be important in the immune response against viruses [Y.-L. Lin and B. A. Askonas, J. Exp. Med. 154, 225 (1981); I. Gardner et al., Eur. J. Immunol. 4, 68 (1974); K. L. Yap and G. L. Ada, Nature 273, 238 (1978); A. J. McMichael et al., New Engl. J. Med. 309, 13 (1983); P. M. Taylor and B. A. Askonas, Immunol. 58, 417 (1986)], efforts have been directed towards the development of CTL vaccines capable of providing heterologous protection against different viral strains. It is known that CTLs kill virallyinfected cells when their T cell receptors recognize viral peptides associated with MHC class I and or class II molecules. These peptides can be derived from endogenously synthesized viral proteins, regardless of the protein's location or function within the virus. By recognition of epitopes from conserved viral proteins, CTLs may provide heterologous protection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Production of therapeutic proteins in transgenic cereal crops Inventor(s): Altosaar, Illimar; (Ottawa, CA), Dudani, Anil; (Ottawa, CA), Ganz, Peter; (Orleans, CA), Sardana, Ravinder; (Ottawa, CA), Tackaberry, Eilleen; (Ottawa, CA) Correspondence: MR. W. Charles Kent; Ridout & Maybee Llp; 19th Floor; 150 Metcalfe ST.; Ottawa; ON; K2p 1p1; CA Patent Application Number: 20030159182 Date filed: August 29, 2002 Abstract: There is provided a herpes virus vaccine produced in in the seeds of a cereal crop and a method of producing the vaccine. The method comprises: a) obtaining a nucleic acid sequence encoding a herpes virus antigen; b) introducing the nucleic acid sequence into cereal plant tissue competent to form seeds; c) permitting said cereal plant tissue to develop; and, d) directing preferential expression of the antigen encoded by the nucleic acid sequence in seeds formed by the cereal plant tissue. Herpes viruses antigens of particular interest include all or antigenic portions of gB (from human cytomegalovirus ("HCMV")), gH (from HCMV), and gD (from herpes simplex virus 1 or 2), as well as antigens from Epstein Barr virus and varicello-zoster virus-8. Envelope glycoproteins from herpes viruses are antigens of interest. Cereal crops of particular interest include rice, wheat, oats, barley, and corn. Vaccines produced according to the invention are very stable and may be administered by a variety of routes, including injection and contact with mucosal membranes, such as by oral administration in purified or unpurified form. Excerpt(s): Human cytomegalovirus ("HCMV") is a widely distributed member of the herpes virus family that is transmitted by blood and other body secretions. In immunocompromised individuals such as AIDS patients, organ transplant recipients and low weight pre-term infants, the virus can cause severe and/or lethal disease, while congenital infection may result in damage to the central nervous system. The HCMV encoded glycoprotein B complex ("gB") is a transmembrane protein of 907 amino acids (for the prototype Towne strain) which is initially synthesized in infected cells as a 105 kDa non-glycosylated polypeptide. In normal infected mammalian host cells, the gB polypeptide undergoes post-translational glycosylation, cleavage of the N-terminal 24 amino acid signal peptide, oligomerization and folding which take place in the endoplasmic reticulum of the cell, where it is transiently associated with a membranebound chaperonin. This results in transport of a 150 kDa gB precursor to the Golgi complex where further carbohydrate modifications occur and the polypeptide is proteolytically cleaved to yield products of 116 kDa and 58 kDa which are disulfide linked. Both species are targets for neutralizing and non-neutralizing antibodies, each representing both continuous and discontinuous epitopes. A phosphorylation site is located in the cytoplasmic tail and may be important for correct intracellular trafficking. The sequence of gB (Towne) is reported in Spaete et al., Virology 167(1), 207 (1988), Pub. Med. Acc. No. M22343. Mammalian immune responses are highly specific and sensitive to even minor differences between potential antigenic sites. Thus, changes to the posttranslational modification of an antigen such as gB will have the potential to render it unsuitable for use as a vaccine against infection by the native organism. Plant seeds are an ideal organ for the targeted synthesis of heterologous proteins. However, where the proteins of interest are of non-plant origin, numerous technical challenges arise in the production and recovery of useful transgenic proteins. In particular, differences in posttranslational modification and transport may render plant-produced proteins unsuitable for some uses in mammals.
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Soluble herpesvirus glycoprotein complex vaccine Inventor(s): Cohen, Gary H.; (Havertown, PA), Dubin, Gary; (La Hulpe, BE), Eisenberg, Roselyn J.; (Haddonfield, NJ), Peng, Tao; (San Diego, CA) Correspondence: Morgan, Lewis & Bockius Llp; 1701 Market Street; Philadelphia; PA; 19103-2921; US Patent Application Number: 20030152583 Date filed: February 20, 2003 Abstract: The invention is directed to a herpes simplex virus vaccine comprising a herpes simplex virus glycoprotein H-glycoprotein L complex. The invention is also directed to a vaccine comprising a DNA encoding a herpes simplex virus glycoprotein H-glycoprotein L complex. Also included is an antibody which specifically binds to a herpes simplex virus glycoprotein H-glycoprotein L complex and DNA encoding the same. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/280,442, filed on Jul. 25, 1994. This invention is directed to herpesvirus vaccines. Herpesviruses are ubiquitous viruses which are the causative agents of numerous diseases in both humans and animals. These viruses are enveloped double stranded icosahedral DNA containing viruses, which envelope is acquired by budding of the nucleocapsid through the inner nuclear membrane. Members of the herpesvirus family which are important human pathogens include herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), and human herpesviruses type 6, type 7 and type 8 (HHV-6, HHV-7 and HHV-8). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Transgenic organisms having transcriptional activators with graded transactivation potential Inventor(s): Baron, Udo; (St. Ilgen, DE), Bujard, Hermann; (Heidelberg, DE), Gossen, Manfred; (El Cerrito, CA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030049842 Date filed: August 3, 2001 Abstract: Transcriptional activators which differ in their activation potential by more than 3 orders of magnitude are provided. The transactivators are fusions between a DNA binding protein (e.g., a Tet repressor) and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). Substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability. Moreover, chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. Various aspects of the invention pertain to nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription.
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Excerpt(s): The ability to regulate gene expression is desirable in a variety of situations, including in the production of recombinant proteins, in gene therapy, and in analyses of cell development and differentiation. A wide variety of gene regulation systems have been described, some of which stimulate gene expression in a constitutive manner and some of which stimulate gene expression in an inducible manner. A popular approach to regulating gene expression is to create a transcriptional activator fusion protein (also referred to herein as a "transactivator") which is composed of a DNA binding domain, which has specificity for a particular target DNA binding site, and a transcriptional activation domain. To regulate expression of a gene of interest, the gene is operatively linked to the target DNA binding site and then both the gene and an expression vector encoding the transactivator fusion protein are coexpressed in a host cell. Upon binding of the transactivator fusion protein to the target DNA binding site, expression of the gene of interest is stimulated. A constitutive transcriptional activator is created in cases where the DNA binding domain binds to its target site constitutively (i e., without the need for an inducing agent to regulate DNA binding). One example of such a constitutive transactivator is GAL4-VP16 (Sadowski, I. et al.(1988) Nature 335:563-564), composed of the yeast GAL4 DNA binding domain linked to the C-terminal region of herpes simplex virus virion protein 16 (Triezenberg, S. J. et al. (1988) Genes Dev. 2:718729). In contrast, when the DNA binding domain only binds to its target site in the presence or absence of an inducing agent, an inducible transcriptional activator is created. Examples of such inducible transcriptional activators are TetR-VP16, composed of a bacterial Tet repressor linked to VP16 (which binds to tetO sequences in the absence, but not the presence of tetracycline) (Gossen, M., and Bujard, H. (1992) Proc. Natl. Acad. Sci. U.S.A 89, 5547-5551) and rTetR-VP16, composed of a mutated Tet repressor linked to VP16 (which binds to tetO sequences in the presence but not the absence of tetracycline) (Gossen, M., et al. (1995) Science 268, 1766-1769). The C-terminal transcriptional activation domain of HSV VP16 has been used frequently as the activator component of transactivator fusion proteins because of its strong capacity to stimulate transcription in eukaryotic cells. It has been shown, however, that overexpression of transcription factors can result in "squelching" (Gill, G., and Ptashne, M. (1988) Nature 334, 721-724), which is seen as a consequence of titrating components of the transcriptional machinery from their respective intracellular pools. For VP16, which is one of the most potent transactivators known, it has been demonstrated that its overexpression, e.g. as a fusion protein with GAL4, is not tolerated by cells (Berger, S. L., et al. (1992) Cell 70, 251-265, Kelleher, R. J., et al. (1990) Cell 61, 1209-1215). Considering that VP16 interacts with a variety of essential components of the transcriptional machinery, including the adaptor/coactivator protein ADA2 in S. cerevisiae (Silverman, N., et al. (1994) Proc. Natl. Acad. Sci. U.S.A 91, 11665-11668) and its human homologue (Candau, R., et al. (1996) Mol. Cell Biol. 16, 593-602), with TFIIB (Lin, Y. S., et al. (1991) Nature 353, 569-571), TFIID (Stringer, K. F., et al. (1990) Nature 345, 783-786), TFIIH (Xiao, H., et al. (1994) Mol. Cell Biol. 14, 7013-7024) and dTAFII40 (Goodrich, J. A., et al. (1993) Cell 75, 519-530), this is not surprising. Gilbert and coworkers (Gilbert, D. M., et al. (1993) Mol. Cell. Biol 13, 462-472) have found a correlation between squelching and growth arrest which indicates that toxicity through squelching is a quantitative problem where the intracellular concentration and the strength of activation domains are crucial parameters. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment and prevention of herpes simplex infections Inventor(s): Ford, Diane; (Irvine, CA), Ford, Larry; (Irvine, CA) Correspondence: Mcguirewoods Llp; Suite 1800; 1750 Tysons Boulevard; Mclean; VA; 22102; US Patent Application Number: 20030153618 Date filed: October 9, 2002 Abstract: We have discovered that the topical application of the amino acid lysine and the 6-methyl derivative of lysine to Herpes simplex virus Type II is therapeutically beneficial and relieves the discomfort and symptoms of HSV infections and prevents or reduces the number of severity of HSV infections. We have also discovered that derivatives of lysine, in addition to 6-methyl lysine and derivatives of arginine have an inhibitory effect upon HSV replication. These compounds are useful in the prevention and treatment of HSV lesions. Excerpt(s): This application claims priority from provisional application serial No. 60/160,875, filed Oct. 22, 1999. This invention relates to the treatment of infections of Herpes simplex viruses (HSV) and more particularly, to the treatment of genital infections of Herpes simplex viruses, i.e., Herpes simplex virus, Type II. For a number of decades, it was believed that Herpes viruses were of only marginal clinical significance. It was generally agreed, for a long period of time, that the Herpes simplex virus (HSV) infections affected mainly children. It was also supposed that these infections produced only mild and self-limited diseases. Over the past two decades, however, this view has been radically changed and it has now been recognized that HSV are known to cause several severe, and sometime life-threatening, diseases in both children and adults. This recognition is the result of and has brought about increased study as to the ways in which HSV infections are spread and has resulted in a very intensive study of means for controlling the spread and treating these infections. It is now known, for example, that HSV infections in newborn infants are frequently devastating and may result in death or permanent injury to the central nervous system. Most HSV infections are Type II and are transmitted venereally or during delivery through a contaminated birth canal. Transmission of HSV from adults with non-genital lesions is less clearly understood but is important in instituting infection control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of tumors with genetically engineered herpes virus Inventor(s): Roizman, Bernard; (Chicago, IL), Weichselbaum, Ralph; (Chicago, IL), Whitley, Richard J.; (Birmingham, AL) Correspondence: Marshall, Gerstein & Borun Llp; 6300 Sears Tower; 233 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030207829 Date filed: September 26, 2001 Abstract: Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus. Excerpt(s): The present invention relates generally to use of modified Herpes simplex viruses as therapeutic treatment for tumors. The development of viruses as anticancer agents has been an intriguing yet elusive strategy. The goal of anticancer viral therapy is
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to inoculate a small percentage of tumor cells with replication competent viruses resulting in viral replication in the targeted tumor cells followed by cellular lysis (oncolysis) and infection of surrounding tumor cells. A key to viral oncolysis is genetic modification of the virus such that replication occurs principally in tumor cells and not in the surrounding normal tissue. Many strategies have focused on the use of genetically engineered viruses for oncolysis. For example, in one approach, attenuated retroviruses, modified to encode herpes simplex virus (HSV) thymidine kinase, were created to target dividing tumor cells [Culver, et al., Science 256:1550-1552 (1992); Ram, et al. Nat. Med. 3:1354-1361 (1997)]. In this technique, however, viral infection of tumor cells was limited since only 10 to 15% of tumor cells were actively progressing through the cell cycle. In another approach, conditional replication-competent adenoviruses (E1b deleted) were designed to replicate only in tumor cells lacking p53, however only 50% of tumors are estimated to contain nonfunctional p53 [Bischoff, et al., Science 274:373-376 (1996); Heise, et al. Nat. Med. 3:639-645 (1997); Hollstein, et al., Science 253:49-53 (1991)]. The success of these strategies, therefore has been limited experimentally only to small tumor xenografts. Recently, genetically engineered replication-competent HSV has been proposed to treat malignant gliomas [Martuza, et al., Science 252:854-856 (1991)]. In antiglioma therapy, HSV-1 mutants were constructed to preferentially replicate in proliferating tumor cells thereby eliminating the risk of widespread dissemination of the virus in the central nervous system, which is observed in rare cases of HSV encephalitis in human. Initial strategies focused on deletion of viral genes encoding enzymes required for viral DNA synthesis (e.g., thymidine kinase, ribonucleotide reductase [Martuza, et al, Science 252:854-856 (1991); Mineta, et al., Cancer Res. 54:3963-3966 (1994)]. More recent studies centered on the use of HSV mutants that lack a newly identified.gamma.sub.134.5 gene involved in neurovirulence [Chou, et al., Science 250:1262-1266 (1990); Chou, et al., Proc. Natl. Acad. Sci. (USA) 89:3266-3270 (1992); Chou, et al., Proc. Natl. Acad. Sci. (USA) 92:10516-10520 (1995); Andreansky, et al. Cancer Res. 57:1502-1509 (1997)]. The combination of previous results suggested that a decrease in viral proliferative potential required for safe intracranial HSV inoculation, however, correlates with a decrease in the oncolytic potential of the virus [Advani, et al. Gene Ther. 5:160-165 (1998)]. The potential therapeutic effects of a genetically engineered HSV, having more potent antitumor efficacy than is possible for intracranial inoculation, has not been studied in models of common human tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Unit dosage forms for the treatment of herpes simplex Inventor(s): Pearson, Don C.; (Lakewood, WA), Richardson, Kenneth T.; (Anchorage, AK) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020197313 Date filed: July 30, 2002 Abstract: The components of this invention are chosen because of their complementarity for the prevention or treatment of diseases caused by the herpes simplex virus. L-Lysine favorably increases the physiologic immunomodulation necessary for defense against this virus. Zinc improves and maintains a normal immune response. 2-Deoxy-2-Dglucose and heparin sodium alter the surface interaction between the herpes virus and the cell, preventing fusion and infectivity. N-Acetyl-L-cysteine increases glutathione
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levels thereby creating a thiol redox barrier to the virus at the cell membrane. Quercetin reduces intracellular replication of the herpes virus and viral infectivity. Ascorbate, in concert with copper and D-.alpha.-tocopherol, provides an antioxidant defense against the herpes virus, which tends to lose latency during period of oxidative, free radical excess. Selenium and quercetin also participate in reducing various oxidative stresses. Together the components of this invention provide the potential for improved resistance to, improved recovery from, and a decreased frequency of recurrence of herpes simplex virus infection. Excerpt(s): This application is related to U.S. Provisional Patent Application No. 60/101,308, filed Sep. 21, 1998, and claims all benefits legally available therefrom. Provisional Patent Application No. 60/101,308 is hereby incorporated by reference for all purposes capable of being served thereby. This invention is in the field of pharmacology, and relates specifically to the pharmacological treatment of conditions associated with herpes simplex virus infections. No human virus is considered normal flora; although some viruses may be more or less symptomatic, unlike bacteria none can be considered non-pathogenic. And because the viral life cycle is played out within a host cell, the membrane and molecular function of the target eukaryocyte and the biological life cycle of the invasive virion are inextricably entwined. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of Cox-2 inhibitors to prevent recurrences of herpesvirus infections Inventor(s): Gebhardt, Bryan M.; (New Orleans, LA), Kaufman, Herbert E.; (New Orleans, LA), Varnell, Emily D.; (New Orleans, LA) Correspondence: Patent Department; Taylor, Porter, Brooks & Phillips, L.L.P; P.O. Box 2471; Baton Rouge; LA; 70821-2471; US Patent Application Number: 20030195242 Date filed: April 15, 2002 Abstract: Selective inhibitors for COX-2 were discovered to prevent the reactivation of viruses that cause latent infections such as herpes simplex virus (HSV-1 and HSV-2). Using mice with a latent infection of HSV, which is subject to reactivation when heatstressed, a selective COX-2 inhibitor (celecoxib) was shown to significantly suppress viral reactivation in the eye when the inhibitor was administered either by intraperitoneal injection or orally. Acetylsalicylic acid, a nonspecific cyclooxygenase inhibitor, was also found to suppress viral reactivation in this heat-stress mouse model. The COX-2 specific inhibitor, celecoxib, was more effective in preventing viral recurrence than was the nonspecific cyclooxygenase inhibitor aspirin. The use of selective inhibitors of COX-2 to inhibit the recurrence of latent viral infections will be more effective and have fewer side effects than the nonspecific inhibitors. In addition, selective inhibitors of COX-2 can be combined with other known antiviral compounds. Excerpt(s): This invention pertains to a method to prevent recurrent infections by herpesviruses, e.g., herpes simplex viruses types 1 and 2, by administering an effective amount of a inhibitor known to be specific for inhibiting the enzyme cyclooxygenase-2 (COX-2). Recurrences due to a latent infection by a herpesvirus are common. The herpesviruses that can cause latent infections include herpes simplex viruses types 1 and 2 (HSV-1 and 2), cytomegalovirus, Epstein Barr virus, and varicella zoster virus. Recurrences due to HSV-1 and 2 are debilitating diseases. Recurrent genital herpes virus infection is painful, transmissible to sexual partners, and emotionally debilitating.
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Recurrent ocular herpetic infection is also painful, potentially transmissible, and may lead to blindness. HSV infections are common throughout the world both in industrialized and underdeveloped countries. To date, vaccines to prevent initial viral infection and prevent recurrent viral infection have not proven to be effective. There is a need for safe and effective prophylactic drugs to prevent recurrent infections of HSV and other herpesviruses. Some of the antivirals in current use, such as acyclovir, famcylovir, and others, have been tested for their capacity to prevent recurrent viral infection in high risk patients. The data resulting from such studies indicate that prophylactic antiviral therapy can reduce but does not eliminate viral recurrences. See Herpetic Eye Disease Study Group, "Oral acyclovir for herpes simplex virus eye disease: Effect on prevention of epithelial keratitis and stromal keratitis," Arch. Ophthalmol., vol. 118, pp. 1030-1036 (2000). However, chronic antiviral therapy is not only expensive, but also may have toxic side effects. Other viral inhibitors are known that act as enzyme inhibitors, e.g., viral thymidine kinase inhibitors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of herpes vectors for tumor therapy Inventor(s): Martuza, Robert L.; (Chevy Chase, MD), Rabkin, Samuel D.; (Chevy Chase, MD), Toda, Masahiro; (Yokohama, JP) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20020127246 Date filed: February 22, 2002 Abstract: Eliciting a systemic antitumor immune response, in a patient who presents with or who is at risk of developing multiple metastatic tumors of a given cell type, entails, in one embodiment, inoculating a tumor in the patient with a pharmaceutical composition consisting essentially of (A) a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells and (B) a pharmaceutically acceptable vehicle for the virus, such that an immune response is induced that is specific for the tumor cell type and that kills cells of the inoculated tumor and of a noninoculated tumor. In another embodiment, the pharmaceutical composition also comprises a defective HSV vector which contains an expressible nucleotide sequence encoding at least one immune modulator. In another embodiment, the pharmaceutical composition contains a second HSV that infects tumor cells but that does not spread in normal cells. According to the latter approach, both the first HSV and the second HSV may have genomes that comprise, respectively, an expressible nucleotide sequence coding for at least one immune modulator. In another embodiment, the pharmaceutical composition comprises, in addition to a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells, a viral vector comprising at least one expressible nucleotide sequence coding for at least one immune modulator. Excerpt(s): Induction of tumor-specific immunity is an attractive approach for cancer therapy because of the prospect of harnessing the body's own defense mechanisms, rather than using standard toxic therapeutic agents, to provide long-term protection against tumor existence, growth and recurrence. This strategy is attractive for its potential to destroy small metastatic tumors which may escape detection, and to provide immunity against recurrent tumors. In principle, an immunotherapy would depend on the presence of tumor-specific antigens and on the ability to induce a cytotoxic immune response that recognizes tumor cells which present antigens.
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Cytotoxic T lymphocytes (CTL) recognize major histocompatibility complex (MHC) class I molecules complexed to peptides derived from cellular proteins presented on the cell surface, in combination with co-stimulatory molecules. Mueller et al., Annu. Rev. Immunol. 7: 445-80 (1989). In fact, tumor-specific antigens have been detected in a range of human tumors. Roth et al., Adv. Immunol. 57: 281-351 (1994); Boon et al., Annu. Rev. Immunol. 12: 337-65 (1994). Some cancer vaccination strategies have focused on the use of killed tumor cells or lysates delivered in combination with adjuvants or cytokines. More recently, gene transfer of cytokines, MHC molecules, co-stimulatory molecules, or tumor antigens to tumor cells has been used to enhance the tumor cell's visibility to immune effector cells. Dranoff & Mulligan, Adv. Immunol. 58: 417-54 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Vanilloid receptor ligands and their use in treatments Inventor(s): Bo, Yunxin Y.; (Thousand Oaks, CA), Chakrabarti, Partha P.; (Simi Valley, CA), Chen, Ning; (Thousand Oaks, CA), Doherty, Elizabeth M.; (Newbury Park, CA), Fotsch, Christopher H.; (Thousand Oaks, CA), Han, Nianhe; (Thousand Oaks, CA), Kelly, Michael G.; (Thousand Oaks, CA), Liu, Qingyian; (Camarillo, CA), Norman, Mark Henry; (Thousand Oaks, CA), Ognyanov, Vassil I.; (Thousand Oaks, CA), Wang, Xianghong; (Moorpark, CA), Zhu, Jiawang; (Simi Valley, CA) Correspondence: U.S Patent Operations/rvp; DEPT. 4300, M/s 27-4-a; Amgen INC.; One Amgen Center Drive; Thousand Oaks; CA; 91320-1799; US Patent Application Number: 20030195201 Date filed: December 10, 2002 Abstract: Compounds having the general structure 1and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders. Excerpt(s): This application claims the benefit of U.S. Provisional Application Nos. 60/339,161 filed Dec. 10, 2001, 60/344,737, filed Dec. 21, 2001, 60/383,331, filed May 22, 2002 and 60/402,422, filed Aug. 8, 2002, which are hereby incorporated by reference. The vanilloid receptor 1 (VR1) is the molecular target of capsaicin, the active ingredient in hot peppers. Julius et al. reported the molecular cloning of VR1 (Caterina et al., 1997). VR1 is a non-selective cation channel which is activated or sensitized by a series of different stimuli including capsaicin and resiniferatoxin (exogenous activators), heat & acid stimulation and products of lipid bilayer metabolism, anandamide (Premkumar et al., 2000, Szabo et al., 2000, Gauldie et al., 2001, Olah et al., 2001) and lipoxygenase metabolites (Hwang et al., 2000). VR1 is highly expressed in primary sensory neurons (Caterina et al., 1997) in rats, mice and humans (Onozawa et al., 2000, Mezey et al., 2000,
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Helliwell et al., 1998, Cortright et al., 2001). These sensory neurons innervate many visceral organs including the dermis, bones, bladder, gastrointestinal tract and lungs; VR1 is also expressed in other neuronal and non-neuronal tissues including but not limited to, CNS nuclei, kidney, stomach and T-cells (Nozawa et al., 2001, Yiangou et al., 2001, Birder et al., 2001). Presumably expression in these various cells and organs may contribute to their basic properties such as cellular signaling and cell division. Prior to the molecular cloning of VR1, experimentation with capsaicin indicated the presence of a capsaicin sensitive receptor, which could increase the activity of sensory neurons in humans, rats and mice (Holzer, 1991; Dray, 1992, Szallasi and Blumberg 1996, 1999). The results of acute activation by capsaicin in humans was pain at injection site and in other species increased behavioral sensitivity to sensory stimuli (Szallasi and Blumberg, 1999). Capsaicin application to the skin in humans causes a painful reaction characterized not only by the perception of heat and pain at the site of administration but also by a wider area of hyperalgesia and allodynia, two characteristic symptoms of the human condition of neuropathic pain (Holzer, 1991). Taken together, it seems likely that increased activity of VR1 plays a significant role in the establishment and maintenance of pain conditions. Topical or intradermal injection of capsaicin has also been shown to produce localized vasodilation and edema production (Szallasi and Blumberg 1999, Singh et al., 2001). This evidence indicates that capsaicin through it's activation of VR1 can regulate afferent and efferent function of sensory nerves. Sensory nerve involvement in diseases could therefore be modified by molecules which effect the function of the vanilloid receptor to increase or decrease the activity of sensory nerves. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Viral stealth technology to prevent T cell-mediated rejection of xenografts Inventor(s): Crew, Mark D.; (Little Rock, AR) Correspondence: Wright, Lindsey & Jennings Llp; Suite 102; 320 North Rollston Avenue; Fayetteville; AR; 72701; US Patent Application Number: 20030118568 Date filed: November 19, 2002 Abstract: The invention comprises exploiting viral stealth mechanisms to eliminate pig MHC class I cell-surface expression. PK(15) (pig kidney) cells stably transfected with the Herpes Simplex Virus (HSV) ICP47 gene [PK(15)-ICP47 cells] exhibited a dramatic reduction of MHC class I cell-surface expression when compared to untransfected PK(15) cells. To test the effect of down-regulation of porcine MHC class I on human cellular immune responses, a human CD8+ enriched T cell line (anti-PK15 T cells) with reactivity towards PK(15) cells was derived by repeated stimulation of human T cells with PK(15) cells stably transfected with the co-stimulatory molecule B7.1 [PK(15)-B7.1 cells]. Anti-PK15 T cells efficiently lysed PK(15) cells but not PK(15)-ICP47 (class I negative) cells. Consistent with effector function, anti-PK15 T cells showed a robust proliferative response to PK(15)-B7.1 cells but did not proliferate at all to PK(15)-B7.1 cells which also expressed HSV ICP47. Excerpt(s): The present application claims the benefit of U.S. Provisional Application No. 60/342,981, filed Dec. 18, 2001, which is incorporated herein by reference. The present invention relates to utilizing virus stealth technology to eliminate pig MHC class I cell-surface expression that hinders the pig-to-human xenotransplantation. Hyperacute rejection (HAR) and delayed xenograft rejection (DXR, also termed acute vascular rejection), are major hurdles to successful pig-to-primate xenotransplantation although
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these phenomena are an almost negligible consideration in allotransplantation (Auchinocloss, H and Sachs DH, Ann Rev Immunol 1998; 16: 433; Cascalho M and Platt J L., Immunity 2001; 14: 437). However, if HAR and DXR can be overcome then xenografts are likely to be rejected by the same mechanisms operative in the rejection of allografts (between HLA-mismatched individuals), that is, in a manner mediated by T cells. In fact, there is ample evidence that human T cells recognize and respond to porcine cells (Dersimonian H, et al., J Immunol 1999; 162: 6993; Xu XC et al., Transplantation 1999; 68: 473; Lalain S, et al., Diabetologia 1999; 42: 330; Yi S, et al., Transplantation 1999; 67: 435; Vallee I, et al., J Immunol 1998; 161: 1652; Brevig T and Kristensen T., Apmis 1997; 105: 290; Yamada K, et al., J Immunol 1995; 155: 5249; Bravery C A et al., Transplantation 1995; 60: 1024) and moreover it is clear that xenoreactive T cells exist at a measurable frequency in "nave" individuals (Hartig C V et al., J Immunol 2000; 164: 2790). 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 herpes simplex, 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 “herpes simplex” (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 herpes simplex. You can also use this procedure to view pending patent applications concerning herpes simplex. 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 HERPES SIMPLEX Overview This chapter provides bibliographic book references relating to herpes simplex. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on herpes simplex include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “herpes simplex” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on herpes simplex: •
Oral Mucosal Disorders Source: Torrance, CA: Homestead Schools, Inc. 2000. 76 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail:
[email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6480. Summary: Oral mucosal disorders are frequently encountered by the practicing dentist. This continuing education program for dentists focuses on oral mucosal disorders. Topics include the causes of chronic nonspecific mucosal lesions; recognized etiologic (causative) agents and their correlation with subtle lesional patterns; drugs commonly associated with lichenoid reactions; various dental materials known to cause oral allergic lesions; differential diagnosis, including medications associated with lichenoid
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reactions, dental materials, common sensitizers in dental materials, foods and oral health care products, atypical lichen planus, and candidiasis; approaches to the classification of oral mucosal lesions; the etiology, appearance, diagnosis, and treatment of the four most common forms of candidosis, i.e., pseudomembranous, erythematosus, hyperplastic, and angular cheilosis; systemic and local factors that predispose a patient to develop candidosis; herpes simplex virus infection and its clinical manifestations; instructions on the proper use of topical steroids for the treatment of minor recurrent aphthous ulcers; the symptoms and diagnosis of recurrent herpetic infection; and over the counter products that can be used for oral ulcerations, including covering agents, local anesthetics, oxygenating agents, and cauteries and antiseptics. The document concludes with a posttest with which readers can qualify for continuing education credit. The document is illustrated with numerous black and white photographs. 15 figures. 13 tables 77 references. •
Oral Manifestations of HIV Infection Source: Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections. San Diego, CA, January 18-20, 1988. Contact: PSG Publishing Company, 545 Great Rd, Littleton, MA, 01460, (508) 486-8971. Summary: These proceedings of the Conference Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections held in San Diego, CA, on January 18-20, 1988. They describe salient features of oral lesions associated with Human immunodeficiency virus (HIV) in dental patients and their importance in diagnosing HIV and Acquired immunodeficiency syndrome (AIDS). Kaposi's sarcoma and other neoplasms are reviewed and their oral manifestations are described. Viral lesions such as Human papillomavirus, herpes simplex virus, varicella virus, and hairy leukoplakia in the oral cavity are examined. Ulcers, salivary gland swelling, and idiopathic thrombocytopenic purpura lesions associated with HIV-associated oral manifestations are described. It is concluded that the varied nature and important implications of oral lesions associated with HIV-positive dental patients are among the factors that make an understanding of oral soft tissue diseases increasingly important in health care.
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Guidelines for Perinatal Care Source: Guidelines for Perinatal Care; 3rd edition, 1992. Contact: American College of Obstetricians and Gynecologists, PO Box 96920, Washington, DC, 20090-6920, (202) 638-5577, http://www.acog.com. American Academy of Pediatrics, Department of Maternal Child and Adolescent Health, Committee on Pediatric AIDS, 141 NW Point Blvd, Elk Grove Village, IL, 60007-1098, (847) 434-4000, http://www.aap.org. Summary: This book chapter focuses on the clinical management of viral and bacterial perinatal infections. These include cytomegalovirus, herpes simplex, the human immunodeficiency virus (HIV), human papillomavirus, human parvovirus, rubella, varicella-zoster, group B streptococcal, listeriosis, syphilis, lyme disease, and chlamydia infection. For each of these infections, guidelines are provided on treatment and counseling during pregnancy, obstetric management, management of exposed newborns, nursery management, and early diagnosis. The section on HIV focuses on diagnostic criteria for adults, children, and infants; prevention; and management after delivery.
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Sexually Transmissible Diseases Source: Guidelines for Women's Health Care; 1996. Contact: American College of Obstetricians and Gynecologists, PO Box 96920, Washington, DC, 20090-6920, (202) 638-5577, http://www.acog.com. Summary: This book chapter reviews the assessment, evaluation, diagnosis, and treatment of sexually transmitted diseases (STDs). The chapter provides an overview and history of the more common STDs followed by guidelines for the treatment of gonorrhea, pelvic inflammatory disease, chlamydia, syphilis, trichomoniasis, herpes simplex virus, human papillomavirus, bacterial vaginosis, candidal vaginitis, hepatitis B, and HIV.
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The Importance of An Interdisciplinary Approach to Prevention of Sexually Transmitted Diseases Source: Research Issues in Human Behavior and Sexually Transmitted Diseases in the AIDS Era. Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. American Society for Microbiology, 1325 Massachusetts Ave NW, Washington, DC, 20005-4171, (202) 942-9295. Summary: This chapter discusses the interdisciplinary approach to the prevention of sexually transmitted diseases (STD's). It questions the existence of a significant health problem in the treatment of nonviral STD's when scientific advancements in the fields of molecular biology and immunology have resulted in diagnostic and therapeutic breakthroughs. It suggests the value of antiviral therapies is minimal, in terms of decreasing overall incidence and prevalence of HIV and herpes simplex virus (HSV) infection; antimicrobial therapy is fundamentally inadequate as a means of total disease control; and effective vaccines are not yet available. The chapter cites social and economic issues as additional causes of STD's in society. It describes the activities of health care providers, clinical and molecular microbiologists, epidemiologists, psychologists, and sociologists as they relate to the prevention and treatment of STD's. Finally, the authors observe that solutions to some of the problems confronting people studying STD's require an integration of disciplines. They believe that collaboration, effective communication, and an understanding of the limitations of one's own area of expertise will result in the formulation of creative, innovative strategies for intervention, prevention, and control.
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Ethical Considerations for Providing Health Care to HIV-Infected Individuals Source: Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections. San Diego, CA, January 18-20, 1988. Contact: PSG Publishing Company, 545 Great Rd, Littleton, MA, 01460, (508) 486-8971. Summary: This chapter of the Conference Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections held in San Diego, CA, on January 18-20, 1988, on diagnosing lesions associated with infection by the Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS), concentrates on case studies of oral Kaposi's sarcoma, herpetic lesions in HIVpositive persons, and HIV-associated gingivitis and periodontal diseases. The incidence of hairy leukoplakia in lower socioeconomic groups, particularly the drug-using population, is appraised. Demonstrations of the HIV in gland saliva are discussed.
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Among oral manifestations of pediatric AIDS, candidiasis, HIV-associated gingivitis, herpes simplex, herpes zoster, and a number of parotid enlargements have been observed. However, pediatric Kaposi's sarcoma or other neoplasms have not been observed. Differentiating between perinatal versus transplacental transmission of pediatric AIDS is also a topic of discussion. Squamous cell carcinoma in homosexual males and HIV-positive women is compared, as well as pap smears on HIV-positive women who are sexual partners of HIV-positive men and HIV negative women who are sexual partners of HIV-positive men. •
Directory of Chicago HIV/AIDS Clinical Trials. Translated title Contact: AIDS Foundation of Chicago, 411 S Wells Ste 300, Chicago, IL, 60607-3924, (312) 922-2322, http://www.aidschicago.org. Test Positive Aware Network, 5537 N Broadway, Chicago, IL, 60640, (773) 989-9400, http://www.tpan.com. African American AIDS Network, 1307 S Wabash Ave 2nd Fl, Chicago, IL, 60605, (773) 371-0032. Summary: This directory provides access to clinical trials related to Acquired immunodeficiency syndrome (AIDS) in the Chicago area. It explains what clinical trials are and the Food and Drug Administration (FDA) approval process, and answers questions about drug studies. The entries include information on anemia, anorexia, cytomegalovirus (CMV) retinitis, meningitis, herpes simplex, histoplasmosis, Human immunodeficiency virus (HIV) infection, Kaposi's sarcoma, lymphoma, mycobacterial prophylaxis, Pneumocystis carinii pneumonia (PCP), and toxoplasma, and studies on women and children.
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AIDS and Infections of Homosexual Men Contact: Butterworth Heinemann Publishers, 225 Wild Wood Ave, Woburn, MA, 01801, (800) 366-2665. Summary: This monograph details clinical information on infections related to Acquired immunodeficiency syndrome (AIDS) that occur in homosexual men. The first section examines nondiarrheal Sexually transmitted disease (STD's), such as syphilis and proctitis due to Chlamydia trachomatis, and also examines the relationship of Human immunodeficiency virus (HIV) infection to infections with pathogenic neisseria. In the second section, authors turn to diarrheal STD's, including gay bowel syndrome, bacterial diarrhea, parasitic infectious diseases, cryptosporidiosis, isosporiasis, and microsporidiosis. The third section studies other STD's, beginning with Hepatitis B transmission as a model for AIDS. It also studies herpes simplex virus infection, cytomegalovirus infection in both healthy and immune deficient homosexual men, and laboratory diagnosis of STD's and opportunistic infections. The fourth section looks at infectious and neoplastic complications. It opens with a chapter on HIV as the etiologic agent of AIDS, then gives a revision of the Centers for Disease Control and Prevention (CDC) surveillance case definition for AIDS. The section also includes chapters on surveillance and epidemiology in the U.S between 1981 and 1985; clinical manifestations of Kaposi's Sarcoma and its treatment; neurology in AIDS; AIDS in prostitutes, children, and prisoners; AIDS in Europe; and opportunistic infections and their treatment. The fifth section turns to immunologic evaluation methods and controls, such as analysis of mechanisms of immune suppression. It also deals with immunologic responses, epidemiologic observations of immunologic abnormalities, immunogenetic findings in patients with Kaposi's Sarcoma, the significance of endogenous interferon and interferon-induced enzymes in patients with AIDS, and approaches to AIDS therapy. The sixth and final section provides a diagnostic perspective.
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Clinician's Guide to Treatment of Common Oral Conditions. 4th ed Source: Baltimore, MD: American Academy of Oral Medicine (AAOM). 1997. 30 p. 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 monograph is intended as a handy, quick reference to the etiologic factors, clinical description, and currently accepted therapeutic management of common oral conditions. Conditions covered include chapped or cracked lips, cheilitis/cheilosis, candidiasis, denture sore mouth, burning mouth syndrome, taste disorders, xerostomia (dry mouth), gingival enlargement, recurrent aphthous stomatitis, erosive lichen planus, pemphigus and pemphigoid, herpes simplex, and varicella zoster (shingles). For each topic, the authors provide a summary of the etiology and treatment and detailed information about prescription drugs used to treat the condition. The monograph also includes information on the management of patients receiving antineoplastic agents, radiation therapy, and chemotherapy. 46 references. (AA-M).
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Sexually Transmitted Diseases: Problems in Primary Care Contact: Practice Management Information Corporation, 4727 Wilshire Blvd Ste 300, Los Angeles, CA, 90010, (800) 633-7467. Summary: This monograph provides basic and practical information on sexually transmitted diseases (STDs). It is designed for physicians, particularly those practicing family and emergency medicine. The monograph describes how various STDs are spread and exactly what is meant by safe sexual practices. It covers the many types of venereal disease (VD) currently prevalent, as well as non-VD infections that can be spread by sexual contact. Each chapter deals with one type of disease, or groups of closely related diseases or infections. Methods of recognizing, treating, and preventing each disease are covered. The effectiveness and outcome statistics for treatments are discussed, with effectiveness based on current sensitivities of the infecting organism. The type of the organism and its life cycle are described. Chapters on the "classic" STDs include: gonorrhea, syphilis, lymphogranuloma venereum, and chancroid. Other chapters discuss: HIV infection, herpes simplex, cytomegalovirus (CMV), human papilloma virus (HPV), hepatitis, and chlamydia. The monograph also contains information concerning related topics such as management of rape victims and contraception.
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 “herpes simplex” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “herpes simplex” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “herpes simplex” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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Chemotherapy of herpes simplex virus infections; ISBN: 0125317603; http://www.amazon.com/exec/obidos/ASIN/0125317603/icongroupinterna
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Genital Herpes by Yehudi M. Felman, et al; ISBN: 089278153X; http://www.amazon.com/exec/obidos/ASIN/089278153X/icongroupinterna
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Genital herpes (SuDoc HE 20.3252:SE 9/3/992/GENITAL) by U.S. Dept of Health and Human Services; ISBN: B00010CTTE; http://www.amazon.com/exec/obidos/ASIN/B00010CTTE/icongroupinterna
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Genital Herpes: What It Is and What to Do About It by Ros Asquith (Illustrator); ISBN: 1854484842; http://www.amazon.com/exec/obidos/ASIN/1854484842/icongroupinterna
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Herpes Simplex [DOWNLOAD: MICROSOFT READER] by T. Natasha Posner (1997); ISBN: B0000W63TU; http://www.amazon.com/exec/obidos/ASIN/B0000W63TU/icongroupinterna
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Herpes simplex encephalitis by L. S. Illis; ISBN: 0856080055; http://www.amazon.com/exec/obidos/ASIN/0856080055/icongroupinterna
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Herpes Simplex Infections of the Eye (Contemporary Issues in Opthalmology, Vol 1) by Frederick C. Blodi (Editor); ISBN: 0443083398; http://www.amazon.com/exec/obidos/ASIN/0443083398/icongroupinterna
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Herpes simplex varicella and zoster: clinical manifestations and treatment by B. E. Juel-Jensen; ISBN: 0397581017; http://www.amazon.com/exec/obidos/ASIN/0397581017/icongroupinterna
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Herpes Simplex Virus; ISBN: 3540550666; http://www.amazon.com/exec/obidos/ASIN/3540550666/icongroupinterna
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Herpes Simplex Virus (Bloomsbury Series in Clinical Science) by Adrian Mindel; ISBN: 0387195491; http://www.amazon.com/exec/obidos/ASIN/0387195491/icongroupinterna
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Herpes Simplex Virus Protocols by S. Moira Brown (Editor), et al; ISBN: 0896033473; http://www.amazon.com/exec/obidos/ASIN/0896033473/icongroupinterna
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Herpes Simplex Virus: Pathogenesis, Immunobiology and Control (Current Topics in Microbiology and Immunology, No 179) by B.T. Rouse (Editor), et al; ISBN: 0387550666; http://www.amazon.com/exec/obidos/ASIN/0387550666/icongroupinterna
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Herpes Simplex/the Self-Help Guide to Managing the Herpes Virus (Thorsons Health) by Philippa Harknett; ISBN: 0722529821; http://www.amazon.com/exec/obidos/ASIN/0722529821/icongroupinterna
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Herpes Simplex: A Complete Cure? by Charlene Pan; ISBN: 0940178125; http://www.amazon.com/exec/obidos/ASIN/0940178125/icongroupinterna
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Immunobiology of Herpes Simplex Virus Infection by Barry t Rouse (Editor); ISBN: 0849360374; http://www.amazon.com/exec/obidos/ASIN/0849360374/icongroupinterna
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Immunobiology of Infection With Herpes Simplex Virus by Holger Kirchner (1982); ISBN: 3805535171; http://www.amazon.com/exec/obidos/ASIN/3805535171/icongroupinterna
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Latency by Herpes Simplex Viruses: Journal: Intervirology, 1991, Vol. 32 by R. W. Whitley (Editor), Kenneth I. Berns (Editor) (1991); ISBN: 3805553625; http://www.amazon.com/exec/obidos/ASIN/3805553625/icongroupinterna
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Peak Immunity: How to Fight Cebv, Candida, Herpes Simplex Viruses and Other Immuno-Suppressed Conditions and Win by Luc, M.D., Ph.D., Lic.Ac., C.Hom., D.I.Hom De Schepper; ISBN: 0961473428; http://www.amazon.com/exec/obidos/ASIN/0961473428/icongroupinterna
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Understanding Genital Herpes (Women's Health Care) by Gilles R. Monif, Gilles R. G. Monid; ISBN: 1880906384; http://www.amazon.com/exec/obidos/ASIN/1880906384/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “herpes simplex” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
A review of photodynamic therapy for herpes simplex;benefits and potential risks. By Larry E. Bockstahler, C. David Lytle [and] Kiki B. Hellman. Author: Bockstahler, Larry B.; Year: 1977; Rockville, Md., U. S. Bureau of Radiological Health, 1974
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Chemotherapy of herpes simplex in animal models with special reference to phosphonoformate, a new antiviral compound Author: Alenius, Stefan.; Year: 1980; Uppsala: [s.n.], 1980; ISBN: 9157604630
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Chemotherapy of herpes simplex virus infections. Author: British Society for Antimicrobial Chemotherapy.; Year: 1978; London; San Francisco: Academic Press, c1977
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Current considerations in the obstetric and gynecologic management of herpes simplex virus infections Author: Gibbs, Ronald S.,; Year: 1972; St. Louis, MO: Journal of Reproductive Medicine, c1986
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Diagnosis and treatment of herpes simplex infections: proceedings of the 1st International Symposium on Tromantadine, Marbella, Spain, March 1986.; Year: 1970; Erlangen: Perimed Fachbuch-Verlagsgesellschaft, c1987; ISBN: 3884292722
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Herpes simplex Author: Posner, T. Natasha,; Year: 1984; London; New York: Routledge, 1998; ISBN: 041510744X http://www.amazon.com/exec/obidos/ASIN/041510744X/icongroupinterna
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Herpes simplex varicella and zoster: clinical manifestations and treatment, by B. E. Juel-Jensen and F. O. MacCallum. Author: Juel-Jensen, B. E.; Year: 1974; Philadelphia, Lippincott [1972]; ISBN: 0039758107 http://www.amazon.com/exec/obidos/ASIN/0815199058/icongroupinterna
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Membrane proteins of herpes simplex virus infected cells: immunological and biochemical studies Author: Welling-Wester, Sijtske.; Year: 1981; [S.l.: s.n.], 1981
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Serodiagnosis of toxoplasmosis, rubella, cytomegalic inclusion disease, herpes simplex Author: Palmer, Dan F.; Year: 1989; Atlanta, Ga.: U.S. Dept. of Health, Education, and Welfare, Public Health Service, Center for Disease Control, Bureau of Laboratories, [1977]
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Treatment of herpes simplex, varicella, and zoster. Author: Norway. Statens legemiddelkontroll.; Year: 1985; Oslo: Norwegian Medicines Control Authority, [1998]
Chapters on Herpes Simplex In order to find chapters that specifically relate to herpes simplex, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and herpes simplex 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 “herpes simplex” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on herpes simplex: •
Gingivitis and Periodontal Disease Source: in McDonald, R.E. and Avery, D.A., eds. Dentistry for the Child and Adolescent. 7th ed. St. Louis, MO: Mosby, Inc. 2000. p. 440-484. 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: $72.00 plus shipping and handling. ISBN: 0815190174. Summary: Gingivitis, a type of periodontal disease, is an inflammation involving only the gingival (gum) tissues next to the tooth. This chapter on gingivitis and periodontal disease is from a textbook on dentistry for the child and adolescent that is designed to help undergraduate dental students and postdoctoral pediatric dentistry students provide comprehensive oral health care for infants, children, teenagers, and individuals with various disabilities. The authors cover simple gingivitis, including eruption gingivitis, gingivitis associated with poor oral hygiene, and allergy and gingival inflammation; acute gingival disease, including that due to herpes simplex virus infection, recurrent aphthous ulcer (canker sore), acute necrotizing ulcerative gingivitis (ANUG), acute candidiasis (thrush, a fungal infection), and acute bacterial infections; chronic nonspecific gingivitis; chlorhexidine as a therapeutic plaque control agent; conditioned gingival enlargement, including puberty gingivitis, fibromatosis, and phenytoin (Dilantin) induced gingival overgrowth; scorbutic gingivitis (associated with vitamin C deficiency); periodontal diseases in children, including periodontitis, premature bone loss in primary dentition, Papillon Lefevre syndrome (precocious periodontosis), gingival recession, the differential diagnosis of self mutilation, abnormal frenum attachment, and frenectomy; the clinical assessment of oral cleanliness and
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periodontal disease; extrinsic stains and deposits on teeth; and dental calculus (seen with low frequency in children). 44 figures. 93 references. •
Viral Diseases Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 88-123. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: Many viral diseases present with oral lesions. This lengthy chapter, from a textbook on diseases of the oral mucosa and the lips, discusses the etiology, clinical features, histopathology, diagnosis, and differential diagnosis for a variety of viral diseases. Diseases covered include herpes simplex, primary herpetic gingivostomatitis, recurrent herpes simplex, eczema herpeticum, varicella, herpes zoster, herpangina, acute lymphonodular pharyngitis, hand-foot-and-mouth disease, hoof-and-mouth disease, vesicular stomatitis, smallpox, vaccinia, orf, measles, rubella, infectious mononucleosis, mumps, human papillomavirus, oral squamous papilloma, verruca vulgaris, condyloma acuminatum, focal epithelial hyperplasia (Heck's disease), molluscum contagiosum, Kawasaki's disease, HIV infections, and AIDS. Full-color photographs illustrate the chapter; references are provided for each section. 56 figures. 189 references. (AA-M).
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Neonatal Hepatitis Source: in Wyllie, R. and Hyams, J.S., eds. Pediatric Gastrointestinal Disease. 2nd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 553-567. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522 or (314) 4537010. Fax (800) 568-5136 or (314) 453-7095. E-mail:
[email protected]. Website: customerservice.wbsaunders.com. PRICE: $155.00 plus shipping and handling. ISBN: 0721674615. Summary: Neonatal hepatitis is a syndrome of symptoms, signs, and hepatic (liver) histology that includes many types of neonatal disease of infectious, genetic, toxic, and metabolic origin. This chapter on neonatal hepatitis in children is from a medical textbook that covers all facets of clinical pediatric gastrointestinal disease. The text emphasizes a clinical focus and incorporates anatomy and physiology considerations into each chapter rather than a separate section. During the neonatal period, infants are susceptible to cholestasis (reduction in bile flow resulting in accumulation in the tissues) resulting from a variety of insults, including infections, drugs, and ischemia (decrease of oxygenated blood to an organ). The chapter covers evaluation and differential diagnosis, giant cell hepatitis, congenital infections, viral infections (cytomegalovirus, herpes simplex virus, rubella, enteroviruses, hepatitis A, B, C, D, and E, human immunodeficiency virus), bacterial infections (syphilis and others), parasitic infections (toxoplasmosis), familial intrahepatic cholestasis, Alagille syndrome (arteriohepatic dysplasia), progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, neonatal cholestasis associated with total parenteral nutrition (TPN), and miscellaneous causes of neonatal hepatitis or cholestasis, including vascular disorders of the liver, drug hepatotoxicity, inspissated bile syndrome (often due to cystic fibrosis), ischemia, endocrine disorders, chromosomal disorders, neonatal lupus erythematosus.
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The authors conclude with a brief discussion of the complications and management of neonatal hepatitis and cholestasis. 8 tables. 166 references. •
Therapeutic Management of Common Oral Lesions Source: in Little, J.W.; Falace, D.A. Dental Management of the Medically Compromised Patient. 4th ed. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 556-569. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $39.95 plus shipping and handling. ISBN: 0801668379. Summary: This appendix, from a handbook on the dental management of medically compromised patients, serves as a quick reference to currently accepted therapeutic management of common oral lesions. The authors note that while there is no cure for many of these lesions, the treatment regimens listed are designed to relieve discomfort, to shorten the clinical duration, and, in some cases, to delay recurrences. Topics include primary herpetic gingivostomatitis; recurrent (orofacial) herpes simplex; varicella zoster (shingles); recurrent aphthous stomatitis (RAS); candidiasis; cheilitis and cheilosis; denture sore mouth; xerostomia; erosive lichen planus; pemphigus and phemphigoid; burning mouth syndrome; chapped or cracked lips; gingival enlargement; and taste disorders. The appendix concludes with a section on the management of patients receiving antineoplastic agents and radiotherapy. A patient education sheet summarizing the oral regimen for patients receiving chemotherapy and radiotherapy is included. 43 references.
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Typical and Atypical Viruses in the Aetiology of Senile Dementia of the Alzheimer Type Source: in Ulrich, J., ed. Histology and Histopathology of the Aging Brain. Basel, Switzerland: S. Karger AG. 1988. p. 119-139. Contact: Available from S. Karger AG. 26 West Avon Road, Box 529, Farmington, CT 06085. (203) 675-7834. PRICE: $148.00. ISBN: 3805547714. Summary: This book chapter attempts to summarize the evidence concerning the involvement of viruses in senile dementia of the Alzheimer's type (SDAT). Such evidence currently is scanty and circumstantial. Particular attention is given to investigative approaches which have been used, and to the possible significance of the establishment of an infection of Herpes simplex virus in the brain. It is concluded that current evidence for the involvement of viruses in the etiology of SDAT is preliminary and inconclusive; however, due to suggestive findings, further investigations are warranted. 77 references.
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Viral Arthritis Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 552-560. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals focuses on viral causes of arthritis. Virus-host interactions are examined. The viral pathogenesis of arthritis is explained. The structure, epidemiology, clinical and rheumatic manifestations, pathogenesis, diagnosis, treatment, and outcome of various viruses or virus vaccines are discussed.
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These viruses or vaccines include rubella and the rubella vaccine, human parvovirus B19, hepatitis B and hepatitis B vaccine, mumps, and arboviruses. In addition, enteroviruses, variola and vaccinia viruses, adenovirus, varicella-zoster, Epstein-Barr virus, herpes simplex virus, and cytomegalovirus are described. 45 references. •
Oral Manifestations of HIV Infection and AIDS Source: in Merigan, T.C., Jr.; Bartlett, J.G.; Bolognesi, D., eds. Textbook of AIDS Medicine. 2nd ed. Baltimore, MD: Williams and Wilkins. 1999. p. 521-535. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672. Fax (800) 447-8438. E-mail:
[email protected]. Website: www.wwilkins.com. PRICE: $155.00. ISBN: 0683302167. Summary: This chapter from a textbook of AIDS medicine focuses on the oral manifestations of HIV infection and AIDS. Topics include epidemiology, including the significance of oral manifestations, the prevalence, incidence, and classification of these findings; neoplasms, including Kaposi's sarcoma, lymphoma, and oral cancer; fungal lesions, including oral candidiasis, erythematous candidiasis, pseudomembranous candidiasis, and angular cheilitis; viral lesions, including herpes simplex, varicella zoster virus (VZV), cytomegalovirus, hairy leukoplakia, and papillomavirus lesions; bacterial infections, including periodontal diseases such as gingivitis and necrotizing ulcerative periodontitis; idiopathic or autoimmune lesions, including recurrent aphthous ulcers, HIV-associated salivary gland disease, immune thrombocytopenic purpura, and abnormal pigmentation; the oral complications associated with pediatric HIV infection; and other oral problems associated with HIV infection. For each condition discussed, the authors report symptoms, diagnosis, and basic management strategies, including drug therapy where appropriate. The authors conclude that initial clinical impressions concerning the frequency of oral lesions and their place in the natural history and progression of HIV disease and AIDS have been supported by a substantial number of studies. However, standardized classification schemes, definitions, and diagnostic criteria are far from being applied universally. 12 figures. 1 table. 191 references.
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Acquired Mucosal Disorders Source: in Scully, C., et al. Color Atlas of Orofacial Health and Disease in Children and Adolescents. London, England: Martin Dunitz Ltd. 2002. p.123-173. Contact: Available from Martin Dunitz Ltd, The Livery House. 7-9 Pratt Street, London, England NW1 0AE. 4404074822202. Website: www.dunitz.co.uk. Email:
[email protected]. PRICE: $125.00 plus shipping and handling. ISBN: 1841841021. Summary: This chapter on acquired mucosal disorders is from a full-color atlas that covers the presentation of the common orofacial disorders and a wide range of less common and some rare disorders. The chapter begins with an overview of common complaints associated with acquired mucosal disorders, including lumps and swellings, pigmented lesions, red lesions, ulcers, and white lesions. The chapter then covers acute candidosis (thrush, candidiasis, moniliasis), amalgam and other tattoos, angioedema, angular stomatitis (angular cheilitis), aphthae (recurrent aphthous stomatitis), Behcet's syndrome, bites, burns, carcinoma, chapped lips, check-chewing, cheilitis, choristoma, Crohn's disease, deep mycoses, erythema multiforme, exfoliative cheilitis, furred tongue, celiac disease (gluten-sensitive enteropathy), hand, foot and mouth disease, herpangina, herpes simplex infections, human papillomavirus infections, iatrogenic
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injury, impetigo, infectious mononucleosis, keratosis, Langerhans cell histiocytosis, lichenoid lesions, lingual papillitis, lip fissures, lupus erythematosus, lymphoepithelial cyst, lymphoma, macroglossia and microglossia, measles (rubeola), median rhomboid glossitis, melanotic macule, melanocytic nevus, molluscum contagiosum, orofacial granulomatosis, papillary hyperplasia, pemphigus vulgaris, pyostomatitis vegetans, scleroderma, self-mutilation, syphilis, traumatic ulcers, and varicella-zoster virus infections (chickenpox). Full-color photographs are accompanied by brief text entries describing each condition and noting diagnostic and management considerations for each. 107 figures. 8 tables. •
Acute Mucogingival Inflammatory Conditions Source: in Montgomery, M.T.; Redding, S.W., eds. Oral-Facial Emergencies: Diagnosis and Management. Portland, OR: JBK Publishing, Inc. 1994. p. 127-158. 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: 0945892055. Summary: This chapter on acute mucogingival inflammatory conditions is from an emergency room handbook that addresses a variety of orofacial injuries that are likely to be encountered in an acute care setting. The author notes that these conditions are probably the most common presenting complaint of patients excluding toothache. Despite the wide spectrum of pathology included in this group, the clinical presentation for many of these lesions is surprisingly limited. Erythema, swelling and ulceration are frequently the mucosal changes noted; the diagnosis can often be challenging. Topics include recurrent aphthous stomatitis (RAS) or canker sores; herpes simplex virus; traumatic ulcers; candidiasis; acute necrotizing ulcerative gingivitis (ANUG); neoplasms, including Kaposi's sarcoma; mucositis; reactive mucosal lesions; vesiculobullous and erosive diseases; systemic infectious diseases; and HIV-associated lesions. The chapter concludes with a table of medications that can be used to treat oral lesions. Each condition is illustrated with a black and white photograph. 16 figures. 19 references.
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Congenital Hearing Impairment Source: in Mencher, G.T.; Gerber, S.E.; McCombe, A. Audiology and Auditory Dysfunction. Needham Heights, MA: Allyn and Bacon. 1997. p. 117-142. Contact: Available from Allyn and Bacon. 160 Gould Street, Needham Heights, MA 02194-2310. (800) 278-3525; Fax (617) 455-7024; E-mail:
[email protected]; http://www.abacon.com. PRICE: $46.95 plus shipping and handling. ISBN: 0205161014. Summary: This chapter on congenital hearing impairment is from an audiology textbook on auditory dysfunction. After a brief discussion delineating the differences between congenital and genetic, the author discusses the etiology and pathology of congenital genetic deafness, forms of pathology, and associated anomalies, including integumentary, skeletal, ocular, and other anomalies. The second section of the chapter addresses congenital nongenetic deafness, including viral deafness due to rubella or cytomegalovirus, protozoal infections, and the remaining causes of the TORCHS (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes, and Syphilis) syndrome, i.e., congenital syphilis and herpes simplex virus. The chapter concludes with a discussion of the medical and audiological considerations for patients with congenital hearing impairment. The author notes that audiometric data should not lead to the assumption
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that a profoundly hearing impaired patient should not be provided with amplification. When examining and when providing rehabilitative programming, the audiologist must consider all the special problems of someone who has never had any hearing or never had sufficient hearing to communicate aurally. 2 tables. 11 figures. •
Diseases and Oral Manifestations of Systemic Disease Source: in Pinkham, J.R., et al., eds. Pediatric Dentistry: Infancy Through Adolescence. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 54-67. Contact: Available from W.B. Saunders Company. Book Orders Fulfillment Department, Harcourt Health Sciences, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522. Website: www.wbsaunders.com. PRICE: $69.00 plus shipping and handling. ISBN: 0721682383. Summary: This chapter on diseases and oral manifestations of systemic disease is from a textbook on pediatric dentistry. Topics include herpetic gingivostomatitis, recurrent herpes simplex (herpes labialis), herpes zoster (chicken pox), herpangina, hand, foot and mouth disease, impetigo, scarlet fever, candidiasis, diabetes mellitus, acute lymphoblastic leukemia, sickle cell anemia, histiocytoses (hystiocytosis X), hemophilia (hemophilia A; Factor VIII deficiency), and pediatric human immunodeficiency virus (HIV) infection. For each disease, the author reviews the causative agent, evaluation of the patient, diagnosis, and therapy. The chapter includes illustrative case studies for some of the diseases. The chapter is illustrated with numerous black and white photographs of the conditions under consideration. 9 figures. 3 tables. 41 references.
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Infectious Agents as Aggravating Factors in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 95-98. 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 infectious agents as aggravating factors 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). When patients present with diarrhea, one of the first questions is whether it is an infection or an attack of IBD. Initial symptoms may be very similar, including diarrhea (with or without blood), abdominal pain or cramps, fever, and even arthralgias (pain in the joints). Clinical features that favor infection are acute onset of diarrhea (often greater than 10 bowel movements per day) and fever early in the course. Conversely, IBD usually has a more insidious onset, fewer than 6 bowel movements daily, and early fever is uncommon. Colonoscopic features can suggest infection or UC, but are rarely diagnostic. Mucosal biopsy, however, can be useful in distinguishing acute self-limited colitis or infectious-type colitis from IBD. However, to further complicate matters, infections sometimes can precipitate IBD, and intercurrent (happening at the same time) infections can mimic or induce flares of IBD. This chapter considers infections that mimic IBD, including amebic colitis and chronic infectious colitides (including Entamoeba histolytica and Yersinia); and infections that aggravate IBD, including Campylobacter jejuni, Salmonella, Shigella, Escherichia coli, Clostricium difficile, Cytomegalovirus, Herpes simplex virus, parasites, and mycobacterium. 1 table. 22 references.
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Inflammatory, Reactive, and Infectious Diseases Source: in Marx, R.E.; Stern, D. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 2003. p.17-136. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $ 399.00 plus shipping and handling. ISBN: 0867153903. Summary: This chapter on inflammatory, reactive, and infectious diseases is from a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. After an introductory section about the processes of inflammation and repair, the authors cover inflammatory and reactive diseases, granulomatous diseases, bacterial diseases, fungal diseases, parasitic diseases, and viral diseases. Specific conditions include tuberculosis, sarcoidosis, cheilitis granulomatosis, Crohn disease, acute necrotizing ulcerative gingivitis, osteomyelitis, candidiasis, benign migratory glossitis, herpes simplex infections, herpes zoster, varicella, HIV and AIDS, among many others. For each condition, the authors discuss clinical presentation and pathogenesis, differential diagnosis, diagnostic work-up, histopathology, treatment, and prognosis. Full-color photographs illustrate the chapter. 125 figures. 6 tables.
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Oral Manifestations in Pediatric HIV Infection Source: in Greenspan, J.S.; Greenspan, D., eds. Oral Manifestations of HIV Infection: Proceedings of the Second International Workshop on the Oral Manifestations of HIV Infection. Carol Stream, IL: Quintessence Publishing Company, Inc. 1995. p. 234-239. Contact: Available from Quintessence Publishing Company, Inc. 551 North Kimberly Drive, Carol Stream, IL 60188-1881. (800) 621-0387 or (630) 682-3223; Fax (630) 682-3288; E-mail:
[email protected]; http://www.quintpub.com. PRICE: $64.00 plus shipping and handling. ISBN: 0867152869. Summary: This chapter on oral manifestations in pediatric HIV infection is from the proceedings of the Second International Workshop on the Oral Manifestations of HIV Infection, held in February 1993 in San Francisco, California. The author notes that despite the importance of oral lesions, there are few pediatric studies and the reported prevalence of oral lesions has varied among studies. The chapter covers fungal lesions; viral lesions, notably herpes simplex virus and Epstein-Barr virus; periodontal disease, including gingivitis and periodontitis; salivary gland disease; and neoplasia. The author concludes with a call for multicenter oral studies as an important step in elucidating the pathophysiology and significance of oral lesions in pediatric HIV infection. 44 references.
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Viral Infections Source: in Greenspan, D., et al. AIDS and the Mouth. Copenhagen, Denmark: Munksgaard. 1992. p. 113-134. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail:
[email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 516 plus postage; contact directly for current price in US dollars. ISBN: 8716103211.
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Summary: This chapter on oral viral infections related to HIV is from a medical textbook on the diagnosis and management of oral lesions related to AIDS. The authors cover herpes simplex, varicella zoster virus (chickenpox and herpes zoster), cytomegalovirus, human papillomavirus, and hairy leukoplakia. The section on hairy leukoplakia is the most extensive, considering clinical features, histopathology, etiology and pathogenesis, transformation to AIDS, differential diagnosis, definitive diagnosis, and management of the condition. Full-color photographs illustrate each of the lesions described; some depict lesions before and after treatment. 23 figures. 2 tables. 58 references. •
Orofacial Lesions Source: in Terezhalmy, G.; Batizy, L.G., eds. Urgent Care in the Dental Office: An Essential Handbook. Carol Stream, IL: Quintessence Publishing Company, Inc. 1998. p. 185-208. Contact: Available from Quintessence Publishing Company, Inc. 551 North Kimberly Drive, Carol Stream, IL 60188-1881. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $68.00 plus shipping and handling. ISBN: 0867153237. Summary: This chapter on orofacial lesions is from a manual on urgent care in the dental office. The authors note that pain in the oral cavity may not always be associated with the teeth or periodontium, but rather may be due to oral lesions that are affecting other oral tissues. Sometimes orofacial lesions can cause severe pain and compromise the patient's ability to chew, swallow, and even sleep; in other instances, the lesions may be a source of great concern, especially for the cancerphobic (afraid of getting cancer) individual. The author first reviews the diagnostic and therapeutic approach recommended for orofacial lesions, and then discusses various possible etiologies. These include: squamous cell carcinoma, traumatic ulcers, recurrent aphthous stomatitis, xerostomia (dry mouth), glossodynia (burning mouth syndrome), herpes simplex virus infections, recurrent varicella zoster infection (shingles), herpangina and hand-foot-andmouth disease, oral candidiasis (thrush), erythema multiforme, and lichen planus. For each oral lesion the authors provide a brief description (and usually a color photograph), and an outline of signs and symptoms, diagnosis, and recommended emergency treatment. 16 figures. 16 references.
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Diagnosis and Management of Soft-Tissue Lesions Source: in Oral Health Care for Adults, Adolescents, and Children with HIV Infection. New York, NY: AIDS Institute, New York State Department of Health. 1998. p. 6-1 to 617. Contact: Available from New York State Department of Health. AIDS Institute, Director, HIV Educational Materials, 5 Penn Plaza, First Floor, New York, NY 10001. Fax (212) 613-4996. PRICE: Single copy free. Order number 9290. Summary: This chapter on the diagnosis and management of soft tissue lesions is from a handbook that assists dentists, dental hygienists, dental assistants, and primary care providers in providing patients with HIV infection with the most up to date care. The authors emphasize that oral health care is an important component of the overall management of patients with HIV infection. The chapter opens by noting that oral manifestations of HIV infection include candidiasis, hairy leukoplakia, Kaposi's sarcoma, and several different types of oral ulcers, such as atypical herpes simplex ulceration, major aphthous-like ulcers, cytomegalovirus (CMV) related oral ulceration, and ulcers due to histoplasmosis and lymphoma. The chapter then offers specific
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recommendations and discusses their implementation. Topics discussed include oral lesions, oral candidiasis (diagnosis, treatment, and medications), topical medications for angular cheilitis, special considerations for systemic antifungal medications, hairy leukoplakia (diagnosis and treatment), herpes simplex ulceration (diagnosis, treatment, managing acyclovir-resistant herpes simplex), aphthous ulcers, cytomegalovirus infection, Kaposi's sarcoma, salivary gland disease associated with HIV infection (including xerostomia, or dry mouth), human papillomavirus infection, and mucosal melanin pigmentation. 8 references. •
Sensorineural Hearing Loss in Children: Etiology and Pathology Source: in Martin, F.N.; Greer Clark, J., eds. Hearing Care for Children. Needham Heights, MA: Allyn and Bacon. 1996. p. 73-91. Contact: Available from Allyn and Bacon. 160 Gould Street, Needham Heights, MA 02194-2310. (800) 278-3525; Fax (617) 455-7024; E-mail:
[email protected]; http://www.abacon.com. PRICE: $59.00 plus shipping and handling. ISBN: 0131247026. Summary: This chapter on the etiology and pathology of sensorineural hearing loss is from a textbook that focuses on the provision of hearing care for children with hearing loss. Topics covered include the etiologies of congenital hearing loss, including ototoxic drugs, teratogenic drugs, viral infections (maternal rubella, cytomegalovirus, herpes simplex, HIV), toxoplasmosis, erythroblastosis fetalis, and prematurity and birth trauma; the etiologies of acquired hearing loss, including bacterial infections, syphilis, viral diseases, neoplastic disorders (cancer), traumatic injury, acoustic trauma, metabolic disorders, and sudden deafness; monitoring dynamic sensorineural hearing loss in children; and medical diagnosis and treatment strategies. The authors emphasize that health care cost containment and the medical and legal implications of missed or delayed diagnosis of sensorineural hearing loss in children are critical issues for the pediatric otolaryngologist. 3 tables. 134 references. (AA-M).
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Vesiculo-Bullous Diseases Source: in Regezi, J.A. and Sciubba, J.J. Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 1-29. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32821-9854. (800) 545-2522. Fax (800) 874-6418. Website: www.wbsaunders.com. PRICE: $63.95. ISBN: 0721677312. Summary: This chapter on vesiculobullous diseases is from a pathology textbook that presents current concepts of oral and maxillofacial pathology in order to enhance the reader's diagnostic skills through the use of differential diagnosis strategies. The text offers readers detailed guidance of etiology, pathogenesis, clinical features, histopathology, differential diagnosis, and treatment of oral diseases of the mucosa, submucosa, and bone. This chapter covers viral diseases, including herpes simplex virus infections, varicella zoster infections, hand, foot and mouth disease, herpangina, and measles (rubeola); conditions associated with immunologic defects, including pemphigus vulgaris, cicatricial pemphigoid, bullous pemphigoid, dermatitis herpetiformis, and linear IgA disease; and hereditary diseases, including epidermolysis bullosa. 39 figures. 4 tables. 67 references.
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Viral Hepatitis: General Features, Hepatitis A, Hepatitis E and Other Viruses Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.267-283. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on viral hepatitis (liver inflammation) is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers general features of viral hepatitis and then focuses on hepatitis A and hepatitis E (other variants are covered in later chapters) and other viruses that have an impact on the liver. Topics include pathology, clinical types, investigations, differential diagnosis, prognosis, treatment, and follow-up; and specific viruses, including hepatitis A virus, hepatitis E virus, hepatitis G virus, hepatitis TT virus, yellow fever, infectious mononucleosis (Epstein-Barr virus), other viruses (cytomegalovirus, herpes simplex) and hepatitis due to exotic viruses. For each type of virus, the authors review epidemiology, clinical features, diagnostic tests, prevention, and treatment. Each section offers a list of references for additional reading. 15 figures. 4 tables. 89 references.
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Viral Infection Source: in Lamey, P.J.; Lewis, M.A.O. Clinical Guide to Oral Medicine. 2nd ed. Hampshire, United Kingdom: British Dental Journal (BDJ), Stockton Press. 1997. p. 1925. Contact: Available from British Dental Journal (BDJ). Marketing Department, Stockton Press, Houndsmill, Basingstoke, Hampshire, RG21 6XS, United Kingdom. Telephone +44 (0) 1256 351898. Fax +44(0) 1256 328339. PRICE: $41.00. ISBN: 0904588505. Summary: This chapter on viral infection is from a clinical guide to oral medicine. The book is a compilation of pathology photographs designed to improve competence in the recognition of diseases involving the oral and para-oral structures. The book includes summaries of the management of conditions most frequently seen in practice. The authors note that members of the herpes group of viruses are responsible for the majority of viral conditions which present to the dental practitioner. Mucosal ulceration is the most frequent clinical presentation, although viruses not belonging to the herpes group may occasionally be responsible for salivary gland swelling or localized epithelial hyperplasia (overgrowth). Diagnosis of viral infection is important, since treatment which can alleviate symptoms and reduce the likelihood of spread of infection is available. Also, the recognition of intra-oral viral infection can have important implications, since it may be an indication of underlying conditions such as leukemia, HIV infection, or child abuse. Topics include primary herpetic gingivostomatitis, secondary herpes simplex infection, chicken pox, shingles, infectious mononucleosis, salivary gland inclusion disease Coxsackie virus, paramyxoviruses (measles, mumps), papillomaviruses, squamous cell papilloma, condyloma acuminata, verruca vulgaris, focal focal epithelial hyperplasia, and squamous cell carcinoma. Oral viral lesions with an atypical presentation and prolonged duration of viral lesions in the oral cavity may indicate the presence of underlying systemic disease. Full color photographs illustrate the chapter. 17 figures.
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Chapter 195: Skin Inflammation Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 6 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 rashes, sores, and blisters with information on the etiology, symptoms, diagnosis, and treatment of drug rashes, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, and granuloma annulare. Drug rashes are usually allergic reactions to medications. These rashes vary in severity from mild redness with pimples over a small area to peeling of the entire skin. Diagnosis is difficult because rashes have many possible causes. There are no laboratory tests to confirm that a rash results from a drug. Eliminating all but life sustaining drugs is sometimes the only way to determine which drug is causing a rash. Most drug induced rashes resolve when the particular drug is stopped. Toxic epidermal necrolysis is a life threatening skin disease in which the top layer of the skin peels off in sheets. Drug reactions are the cause of this condition in about one third of the cases. People with this condition are hospitalized and taken off the drugs that may be implicated. Fluids and salts are replaced intravenously, but use of corticosteroids is controversial. Erythema multiform is characterized by patches of red, raised skin distributed symmetrically over the body. Causes include herpes simplex, drugs, and other infectious diseases. Erythema multiforme usually resolves on its own. Any infectious cause is treated, and any drugs causing the condition are eliminated. Erythema nodosum is an inflammatory disorder that produces tender red bumps under the skin, usually on the shins. This disorder may be a sign of some other disease or of sensitivity to a drug. Biopsy of a nodule can help in making a diagnosis. Treatment involves stopping any drugs that might be causing the disorder and treating any underlying infection. Granuloma annulare, a chronic skin condition of unknown cause, is characterized by small, firm, raised bumps that form a ring with normal or slightly sunken skin in the center. The condition usually heals without any treatment. 1 table.
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Esophageal Infections Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 237-243. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter, from a gastroenterology text, covers esophageal infections. The authors note that infectious esophagitis was previously regarded to be rather uncommon; however, the AIDS epidemic has dramatically changed this perception and is probably the single most important factor accounting for the increasing incidence of infectious esophagitis. Growing numbers of immunosuppressed organ transplant patients also provide an at-risk population. These infections are responsible for serious morbidity and mortality in compromised patients. Most patients with esophageal infections present with odynophagia or dysphagia. Although reflux esophagitis is generally not a predisposing factor, other causes of esophagitis such as radiation therapy or cytotoxic chemotherapy may be responsible for symptoms in this group of patients or may provide a portal of entry for infection to occur. Still, gastroesophageal reflux disease, pill-induced esophageal injury, pericardial disease, and myocardial
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ischemia must be considered in the differential diagnosis of acute odynophagia and dysphagia. The authors discuss the infections by cause (fungi, viruses, and bacteria) and review the clinical presentation, diagnosis, and therapeutic options for each. They note that Candida albicans and herpes simplex virus are the most commonly encountered pathogens, although a number of other agents including cytomegalovirus (CMV), Aspergillus, and tuberculosis may infect the esophagus. 2 tables. 26 references. (AA-M). •
Treatment of Oral Manifestations Source: in Greenspan, D., et al. AIDS and the Mouth. Copenhagen, Denmark: Munksgaard. 1992. p. 159-170. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail:
[email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 516 plus postage; contact directly for current price in US dollars. ISBN: 8716103211. Summary: This chapter, from a medical textbook on the diagnosis and management of oral lesions related to AIDS, discusses the treatment of oral manifestations that are associated with AIDS. In general, no significant problems have been reported with routine dental care, including restorative dentistry, endodontics, minor orthodontics, and minor oral surgery. Referrals should be made to appropriately trained periodontists and oral medicine specialists for diagnosis and care of oral mucosal and periodontal HIV-associated lesions. The authors outline the current strategies for treating HIV, noting that certain medications used to treat HIV infection or HIV-related conditions may interfere with dental care. The authors then briefly discuss the treatment for fungal infections (including oral candidiasis), HIV-periodontal diseases, viral lesions (herpes simplex, herpes zoster, hairy leukoplakia, and human papillomavirus), Kaposi's sarcoma, lymphoma, recurrent aphthous ulceration, and xerostomia. Full-color photographs illustrate each of the conditions described; some depict lesions before and after treatment. 16 figures. 1 table. 17 references.
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Infection Source: Cambridge, MA: Harvard University Press. 1991. 13 p. Contact: Available from Harvard University Press. 79 Garden Street, Cambridge, MA 02138-9983. (617) 495-2577 or (617) 495-2480. PRICE: $24.95 plus shipping and handling. ISBN: 067464235X. Summary: This chapter, from a patient education book about organ transplantation, discusses the task of preventing infection in patients who have received donor organs. Topics include the role of good tissue typing and matching in prevention of infection; reducing the risks of infection; preoperative, perioperative and postoperative measures taken to reduce the risk of infection; a timetable used to divide the times when the recipient is susceptible; urinary tract infection; pneumonia; special viral infections including general infections like influenza and those infections for which the transplant recipient faces a higher-than-average risk; the herpes group of viruses, including cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and varicella-zoster virus; hepatitis; and suggestions for reducing the risks of acquiring a contagious disease. The chapter presents detailed medical information about these topics in clear, easy-tounderstand language designed for the layperson.
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Disease of the Eyes and Mouth Source: in Andersen, R.D., et al. Infections in Children: A Sourcebook for Educators and Child Care Providers. 2nd ed. Gaithersburg, MD: Aspen Publishers, Inc. 1994. p.83-89. Contact: Available from Aspen Publishers, Inc. P.O. Box 990, 7201 McKinney Circle, Frederick, MD 21701-9727. Voice (800) 638-8437. PRICE: $36.00 plus shipping and handling. ISBN 0834203871. Summary: This chapter, from a sourcebook on infections in children, is intended to familiarize educators with diseases of the eyes and mouth. Diseases of the eyes included are blepharitis, stye, nasolacrimal (tear) duct obstruction, dacryocystitis, and conjunctivitis. Diseases of the mouth included are thrush (oral moniliasis or candidiasis); herpes simplex infections; hand, foot and mouth disease; herpangina; canker sores (aphthous ulcers); mumps; and dental disease. For each disease, the authors briefly describe the symptoms, cause, and treatment options. 4 references.
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Erythema Multiforme Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 68-70. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses erythema multiforme (EM), a common complex skin disease. As the name suggests, the clinical lesions can take many forms. About 40 percent of EM patients have mucosal involvement. Typically, there may be oral mucosal blisters and erosions; ocular changes including conjunctivitis, uveitis, and scarring; and urethral and genital erosions leading to bowel and urinary retention. EM is self-limited and tends to resolve after two to three weeks. When it is recurrent, it is almost always connected with recurrent herpes simplex. The chapter covers etiology, clinical features, histopathology, diagnosis, differential diagnosis, and therapy. The authors caution that stomatitis caused by medications may appear similar to localized EM. Full-color photographs illustrate the chapter. 5 figures. 13 references. (AA-M).
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Infectious Diseases and Specific Infections Source: in Miller, R.L., et al. General and Oral Pathology for the Dental Hygienist. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 48-80. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $43.00 plus shipping and handling. ISBN: 0801670241. Stock Number 07024. Summary: This chapter, from a textbook on pathology for dental hygiene students, presents a discussion of infectious diseases and specific infections. Topics include the factors that contribute to the virulence of organisms; common host defense factors, including external barriers, inflammation, and internal barriers; the pathogenesis of viral diseases, including the mode of cellular injury; specific viral diseases, including herpes simplex type 1, varicella-zoster virus, Coxsackie virus, mumps, measles, Epstein-Barr virus, and hepatitis; bacterial diseases, including recurrent aphthous stomatitis, chronic
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periodontitis, streptococcal pharyngitis, tuberculosis, and syphilis; fungal diseases, including candidiasis, and deep fungal infections; HIV infection; and special care and treatment-planning procedures necessary to better treat HIV and AIDS patients. The chapter includes a list of learning objectives; illustrative case studies; and recommended readings. 30 figures. 2 tables.
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CHAPTER 8. MULTIMEDIA ON HERPES SIMPLEX Overview In this chapter, we show you how to keep current on multimedia sources of information on herpes simplex. 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 herpes simplex is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “herpes simplex” 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 “herpes simplex” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on herpes simplex: •
This Is a Video About Herpes Contact: Durrin Productions Incorporated, 4926 Sedgwick St NW, Washington, DC, 20016-2326, (202) 237-6700, http://www.durrinproductions.com. Summary: This video, for adolescents, discusses the sexually transmitted disease (STD), herpes simplex virus, its transmission, prevention, symptoms, and treatment. Several teens discuss how it made them feel to learn that they had contracted herpes. The video recommends that anyone who experiences the symptoms of herpes, or who believes that they have been exposed to it, seek medical attention immediately.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html.
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To find audio 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 “Sound Recordings.” Type “herpes simplex” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on herpes simplex: •
Herpesvirus Infection in the Immunocompromised Host: 15th National Lesbian & Gay Health Conference & 11th Annual AIDS/HIV Forum; Houston, TX, July 20-25, 1993 Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This sound recording contains a presentation on the family of herpes viruses, their manifestations, and available treatments. It informs the listener that some of the herpes viruses may be cofactors in the progression of HIV disease. While the primary infection is the most severe, reactivations can occur; the mechanism of reactivation is not understood although stress is thought to be a factor. The family of viruses consists of: Herpes simplex I (oral herpes); herpes simplex II (genital herpes); varicella (chicken pox and shingles); Epstein-Barr (mononucleosis and hairy leukoplakia); herpes VI (believed to be cofactor of HIV); and herpes VII (recently discovered, role unknown). Each type of virus is briefly discussed, both singly and in combination, in both immunocompromised and control hosts. The presentation emphasizes the seriousness of disseminated herpes virus infection.
Bibliography: Multimedia on Herpes Simplex The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in herpes simplex (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on herpes simplex: •
Clinical aspects of genital herpes [videorecording] Source: Department of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1979
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Clinical, laboratory, and therapeutic correlates in Herpes simplex virus keratitis [videorecording] Source: [presented by] American Academy of Ophthalmology; Year: 1981; Format: Videorecording; San Francisco, CA: The Academy, c1981
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Genital herpes simplex infection [slide]: current understanding, diagnosis, and treatment Source: W. Lawrence Drew; Year: 1985; Format: Slide; Garden Grove, Calif.: Medcom, c1985
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Herpes simplex [videorecording] Source: Academy of Health Sciences, Health Sciences Media Division; produced by the Institute for Dermatologic Communication and Education; Year: 1981; Format: Videorecording; San Francisco, Calif.: The Institute, c1981
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Herpes simplex virus infections; Acquired immune deficiency syndrome; Rabies vaccination: changing concepts of prophylaxis and treatment; Imaging receptors in the human brain [videorecording] Source: [presented by] CMESAT; Year: 1986; Format: Videorecording; Sarasota, Fla.: CMESAT, c1986
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Management of herpes simplex in pregnant women and neonates [videorecording] Source: a production of the Office of Health Extension, Public Service and Research for the University of Alabama, School of Medicine, the University of Alabama in Birmingham; produce; Year: 1982; Format: Videorecording; Carrboro, NC: Health Sciences Consortium, c1982
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CHAPTER 9. PERIODICALS AND NEWS ON HERPES SIMPLEX Overview In this chapter, we suggest a number of news sources and present various periodicals that cover herpes simplex.
News Services and Press Releases One of the simplest ways of tracking press releases on herpes simplex 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 “herpes simplex” (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 herpes simplex. 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 “herpes simplex” (or synonyms). The following was recently listed in this archive for herpes simplex: •
HSV-1 may be dominant cause of genital herpes Source: Reuters Medical News Date: November 05, 2003
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Doxorubicin treats herpes simplex in mice via retrograde axon transport Source: Reuters Industry Breifing Date: June 06, 2003
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Some types of genital herpes don't often recur Source: Reuters Health eLine Date: March 13, 2003
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Non-ulcerative genital herpes virus shedding may increase HIV-1 transmission Source: Reuters Medical News Date: January 01, 2003
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Daily suppression of herpes simplex may be important in HIV-infected patients Source: Reuters Industry Breifing Date: December 26, 2002
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Glycoprotein D vaccine effective against genital herpes in some wome Source: Reuters Medical News Date: November 20, 2002
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Glaxo genital herpes vaccine effective in treating certain wome Source: Reuters Industry Breifing Date: November 20, 2002
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Genital herpes may increase cervical cancer risk Source: Reuters Health eLine Date: November 05, 2002
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Genital herpes infection could skyrocket Source: Reuters Health eLine Date: November 01, 2002
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Genital herpes due to HSV-1 increasing in UK, risk tied to adolescent sex Source: Reuters Medical News Date: October 07, 2002
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Acyclovir cream effective for herpes simplex labialis Source: Reuters Industry Breifing Date: July 15, 2002
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Many seem unconcerned about genital herpes: survey Source: Reuters Health eLine Date: May 27, 2002
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Avanir gets SBIR grant to develop genital herpes treatment Source: Reuters Industry Breifing Date: March 20, 2002
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Automated PCR testing recommended for routine genital herpes detection, typing Source: Reuters Medical News Date: March 15, 2002
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New topical treatments for herpes labialis evaluated Source: Reuters Industry Breifing Date: October 10, 2001
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Condoms cut women's risk of genital herpes Source: Reuters Health eLine Date: June 26, 2001
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Novactyl cleared to begin trials of herpes labialis compound Source: Reuters Industry Breifing Date: May 24, 2001
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Infection from genital herpes virus soars in US Source: Reuters Health eLine Date: May 23, 2001
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Acyclovir cream reduces duration and pain of herpes simplex labialis episodes Source: Reuters Industry Breifing Date: April 11, 2001
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Digene receives expanded NIH funding to develop herpes simplex diagnostics Source: Reuters Industry Breifing Date: February 06, 2001
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FDA approves human trials of Antigenics' genital herpes candidate Source: Reuters Industry Breifing Date: February 05, 2001
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Resistant herpes simplex virus a concern after stem cell transplant Source: Reuters Medical News Date: November 16, 2000
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First successful genital herpes vaccine candidate is gender-specific Source: Reuters Medical News Date: September 19, 2000
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Zonagen to develop Viragen's Omniferon as topical gel for genital herpes Source: Reuters Industry Breifing Date: August 30, 2000
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Herpes simplex labialis responds better when corticosteroid added to famciclovir Source: Reuters Industry Breifing Date: July 11, 2000
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Herpes simplex virus mutants may benefit patients with malignant glioma Source: Reuters Medical News Date: June 22, 2000
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HSV-1 infection accounts for unexpectedly high proportion of genital herpes Source: Reuters Medical News Date: May 30, 2000
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Immune Network to license potential herpes simplex treatments from Meditech Source: Reuters Industry Breifing Date: May 23, 2000
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.
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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 “herpes simplex” (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 “herpes simplex” (or synonyms). If you know the name of a company that is relevant to herpes simplex, 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 “herpes simplex” (or synonyms).
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 “herpes simplex” (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 herpes simplex: •
Oral Infections in HIV Patients Can Be Destructive Source: Skin and Allergy News. 31(2): 45. February 2000.
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Contact: Available from Skin and Allergy News. 12230 Wilkins Avenue, Rockville, MD 20852. (301) 816-8796. Summary: This article from a newsletter for dermatologists reports on a presentation on common oral infections in patients with HIV disease. The author stresses that extra diligence is required in diagnosing and treating the oral manifestations of bacterial, viral, and fungal infections in patients with HIV, as the lesions of these infections tend to be widely distributed, persistent, and destructive to tissue in this patient population. The author discusses specific infections, including necrotizing stomatitis, bacillary angiomatosis, hairy leukoplakia, herpes simplex, oral candidiasis, and cytomegalovirus. The author briefly reviews the treatment strategies to undertake for each of these infections. 4 figures.
Academic Periodicals covering Herpes Simplex Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to herpes simplex. In addition to these sources, you can search for articles covering herpes simplex that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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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 herpes simplex. 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 non-profit 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 herpes simplex. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to herpes simplex: Acyclovir •
Systemic - U.S. Brands: Zovirax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202008.html
•
Topical - U.S. Brands: Zovirax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202009.html
Calamine •
Topical - U.S. Brands: Calamox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202748.html
Docosanol •
Topical - U.S. Brands: Abreva http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500219.html
Famciclovir •
Systemic - U.S. Brands: Famvir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202723.html
Foscarnet •
Systemic - U.S. Brands: Foscavir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202617.html
Lidocaine •
Topical - U.S. Brands: Lidoderm http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500058.html
Neomycin •
Oral - U.S. Brands: Mycifradin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202396.html
•
Topical - U.S. Brands: Myciguent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202397.html
Penciclovir •
Topical - U.S. Brands: Denavir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203495.html
Spermicides •
Vaginal - U.S. Brands: Advantage 24; Because; Conceptrol Contraceptive Inserts; Conceptrol Gel; Delfen; Emko; Emko Pre-Fil; Encare; Gynol II Extra Strength Contraceptive Jelly; Gynol II Original Formula Contraceptive Jelly; Koromex Cream; Koromex Crystal Clear Gel; Koromex Fo http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202531.html
Valacyclovir •
Systemic - U.S. Brands: Valtrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202790.html
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Vidarabine •
Ophthalmic - U.S. Brands: Vira-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202592.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 Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
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.13 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:14 •
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
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
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). 14 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 “herpes simplex” 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 “herpes simplex” (or synonyms) into the “For these words:” box. The following is a sample result: •
AIDS - Related Herpes Simplex Virus Infection 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 looks at herpes simplex virus (HSV) infection associated with Acquired immunodeficiency syndrome (AIDS). Longstanding HSV infection is considered one of the first symptoms of AIDS, but even on persons with Human immunodeficiency virus (HIV) infection, the sores remained localized. Herpes lesions or sores are caused by two types of viruses; Type 1 causes oral herpes, also known as fever blisters or cold sores, while Type 2 causes genital herpes. In Persons with AIDS (PWA's), strains of herpes that resist treatment are becoming more and more common. Traditionally, acyclovir by mouth or intravenously is used both as a treatment and as a preventive therapy. Even in persons with healthy immune systems, some strains of herpes resist treatment, but that can usually be overcome with higher doses of medicine. However, some HIV-infected persons have herpes lesions that resist even the highest dosage. Foscarnet has shown some success in treating herpes, and presently, the National Institute of Allergy and Infectious Diseases (NIAID) has one clinical trial ongoing which involves it.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 15 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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).
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Type “herpes simplex” (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 30374 220 263 423 0 31280
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “herpes simplex” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 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.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for
17
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 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. 22 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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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/.
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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 herpes simplex 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 herpes simplex. 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 herpes simplex. 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 “herpes simplex”:
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•
Other guides Herpes Simplex http://www.nlm.nih.gov/medlineplus/herpessimplex.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html HPV http://www.nlm.nih.gov/medlineplus/hpv.html Infections and Pregnancy http://www.nlm.nih.gov/medlineplus/infectionsandpregnancy.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Menstruation and Premenstrual Syndrome http://www.nlm.nih.gov/medlineplus/menstruationandpremenstrualsyndrome.ht l Mouth Disorders http://www.nlm.nih.gov/medlineplus/mouthdisorders.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html Sexually Transmitted Diseases http://www.nlm.nih.gov/medlineplus/sexuallytransmitteddiseases.html Shingles http://www.nlm.nih.gov/medlineplus/shinglesherpeszoster.html Viral Infections http://www.nlm.nih.gov/medlineplus/viralinfections.html
Within the health topic page dedicated to herpes simplex, the following was listed: •
General/Overviews Genital Herpes: A Hidden Epidemic Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/202_herp.html Herpes: Get the Facts Source: American Social Health Association http://www.ashastd.org/hrc/educate.html
•
Diagnosis/Symptoms Tests to Diagnose Herpes Source: American Social Health Association http://www.ashastd.org/hrc/hrctest.html
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Treatment Treatment and Therapy Source: American Social Health Association http://www.ashastd.org/hrc/hrctreatment.html
•
Coping When to Tell a Partner Source: American Social Health Association http://www.ashastd.org/hrc/hrcwhentell.html Why Tell a Partner? Source: American Social Health Association http://www.ashastd.org/hrc/hrcwhytell.html
•
Specific Conditions/Aspects Cold Sore Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00358
•
Children Coping with Cold Sores Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/aches/cold_sores.html Herpes Simplex Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/herpes.html
•
Men Herpes during Pregnancy -- What It Means, What to Expect Source: American Academy of Family Physicians http://familydoctor.org/handouts/760.html
•
Organizations American Social Health Association http://www.ashastd.org/ National Center for HIV, STD, and TB Prevention, Division of Sexually Transmitted Diseases Source: Centers for Disease Control and Prevention http://www.cdc.gov/nchstp/dstd/dstdp.html National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/
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Prevention/Screening Condoms and Sexually Transmitted Diseases. Especially AIDS Source: Food and Drug Administration http://www.fda.gov/oashi/aids/condom.html Condoms: Protect Yourself Against STDs and Unwanted Pregnancy Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00463 FDA Updates Labeling of Valtrex Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01250.html New CDC Treatment Guidelines Critical to Preventing Health Consequences of Sexually Transmitted Diseases Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/fs020509.htm Right Way to Use a Condom Source: American Social Health Association http://www.ashastd.org/stdfaqs/condom_a.html
•
Teenagers Genital Herpes (HSV-2) Source: Nemours Foundation http://kidshealth.org/teen/sexual_health/stds/std_herpes.html
•
Women Herpes during Pregnancy -- What It Means, What to Expect Source: American Academy of Family Physicians http://familydoctor.org/handouts/760.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 herpes simplex. 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:
Patient Resources
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Genital Herpes : What You Need to Know Contact: Education Programs Associates, Health Education Resource Center, 1 W Campbell Ave Ste 45, Campbell, CA, 95008, (408) 374-3720, http://www.cfhc.org. Summary: This brochure provides information about the herpes simplex virus, a sexually transmitted disease, for individuals with herpes. The brochure discusses symptoms, methods of transmission, treatment, and prevention. The brochure informs women that herpes can be transmitted to their children during birth and that they should inform their physicians if they have herpes.
•
Herpes Simplex Contact: National Abstinence Clearinghouse, 801 E 41st St, Sioux Falls, SD, 57105, (888) 577-2966, http://www.abstinence.net. Summary: This brochure, for the general public, provides information on the sexually transmitted disease (STD), herpes simplex. It discusses the herpes simplex virus group, how condoms are ineffective against contracting herpes, the epidemiology of this STD, its symptoms, and treatment. The brochure encourages individuals to practice sexual abstinence until marriage to prevent the spread of herpes. It provides a phone number and Web address for individuals to access products and resources related to abstinence until marriage.
•
Recurrent (Orofacial) Herpes Simplex Source: in Rosenberg, S.W., ed., et al. Clinician's Guide to Treatment of Common Oral Conditions. 4th ed. Baltimore, MD: American Academy of Oral Medicine (AAOM). Spring 1997. p. 24. 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 fact sheet outlines recommendations for physicians caring for patients with recurrent orofacial herpes simplex infections. Topics include etiology, clinical description, the rationale for treatment, and prevention strategies. The precipitating factors for this condition include fever, stress, exposure to sunlight, trauma, and hormonal alterations. Treatment should be initiated as early as possible in the prodromal stage with the objective of reducing the duration and symptoms of the lesion. Oral acyclovir, prophylactically as well as therapeutically, may be considered when frequent recurrent herpetic episodes interfere with daily function and nutrition. The fact sheet notes that current FDA recommendation is that systemic acyclovir be used to treat oral herpes only for immunocompromised patients. If a recurrence on the lips is usually precipitated by exposure to sunlight, the lesion may be prevented by the application to the area of over-the-counter sunscreens with a high skin protection factor (SPF 15 or higher). (AA-M).
•
Enfermedades de Transmision Sexual: Herpes (Causado por el Virus Herpes Simplex Tipos 1 y 2, VHS) Contact: Minnesota Department of Health, Infectious Disease Epidemiology Prevention and Control Division, PO Box 9441, Minneapolis, MN, 55440-9441, (612) 676-5414, http://www.health.state.mn.us/divs/dpc/idepc.html.
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Summary: This information sheet presents an overview of genital herpes, including signs and symptoms of the virus, transmission routes and factors, and complications and consequences. These can entail recurrent painful attacks as well as health problems for newborns. The information sheet outlines recommendations to reduce the spread of genital herpes and treatment options. Sources for additional information are provided. •
Genital Herpes (HSV) Contact: Multicultural Health Communication Service, GPO Box 1614, Sydney, http://www.health.nsw.gov.au/health-public-affairs/mhcs. Summary: This pamphlet discusses the sexually transmitted disease (STD), herpes simplex virus (HSV), its transmission, symptoms, treatment, and prevention. It describes the effect of HSV on the body and on pregnancies. The pamphlet also explains why recurrent episodes occur and how often, what to do during a herpes recurrence, and how to reduce the number of occurrences. It illustrates proper use of a condom and provides information on sexual health services in Australia.
•
What You Should Know About Genital Herpes Contact: Texas Department of Health Warehouse, Attn: Literature and Forms, 1100 W 49th St, Austin, TX, 78756, (512) 458-7761. Summary: This pamphlet presents information on genital herpes in response to questions. The pamphlet explains that herpes is caused by the herpes simplex virus (HSV) and that there are two types: HSV-1 and HSV-2. The latter usually causes genital herpes. The pamphlet explains the transmission of genital herpes, symptoms, diagnosis, treatment, prevention, whether herpes increases the risk of getting human immunodeficiency virus (HIV), and its effect on pregnancy and on the infected individual's personal life.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “herpes simplex” (or synonyms). The following was recently posted: •
2002 national guideline for the management of genital herpes Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3035&nbr=2261&a mp;string=herpes+AND+simplex Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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Genital Herpes Summary: Genital herpes is usually spread through sexual contact with someone who has herpes sores in the genital area, but it can also be transmitted by a person who is infected but has no noticeable symptoms Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=102
•
Herpes Simplex and Pregnancy Source: International Herpes Alliance http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5944 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 herpes simplex. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to herpes simplex. By consulting all of associations
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listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with herpes simplex. 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 herpes simplex. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “herpes simplex” (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 “herpes simplex”. 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 “herpes simplex” (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 “herpes simplex” (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.23
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
23
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)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on herpes simplex: •
Basic Guidelines for Herpes Simplex AIDS Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000594.htm Eczema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000853.htm Encephalitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001415.htm Herpes labialis (oral Herpes simplex) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000606.htm Herpes simplex Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001324.htm HSV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001368.htm
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•
Signs & Symptoms for Herpes Simplex Blindness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003040.htm Blister Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Blisters Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Coughing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Erosion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003225.htm Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Genital lesions (female) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003222.htm Genital lesions (male) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003221.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Mouth sores Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003059.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm
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Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Skin lesions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Skin rash or lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Sneezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003060.htm Sore throat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Throat, sore Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Tingling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm Vaginal discharge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003158.htm Vesicles Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm •
Diagnostics and Tests for Herpes Simplex ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm AST Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Culture from endocervix Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003754.htm Oropharynx lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003850.htm
312 Herpes Simplex
Pap smear Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003911.htm Serum antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003333.htm Tzanck test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003837.htm Viral culture of lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003739.htm •
Surgery and Procedures for Herpes Simplex C-section Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002911.htm
•
Background Topics for Herpes Simplex Cervix Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002317.htm Condoms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/004001.htm Conjunctiva Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002326.htm Precipitating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002275.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Safer sex behaviors Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001949.htm Secondary infection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002300.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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HERPES SIMPLEX DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [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] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Aconitine: A alkaloid from the root of Aconitum napellus L. and other aconites. Activates voltage-gated Na+ channels. Has been used to induce arrhythmia in experimental animals. Shows antiinflammatory and antineuralgic properties. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acute Disease: Disease having a short and relatively severe course. [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 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] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [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]
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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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] 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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]
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Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] 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, 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] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [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] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH]
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Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a,
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C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergic: 1. Characterized by abnormal inactivity; inactive. 2. Marked by asthenia or lack of energy. 3. Pertaining to anergy. [EU] 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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anogenital: Pertaining to the anus and external genitals. [EU] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH]
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Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [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] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a
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particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [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] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [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 leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs
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to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiologist: Study of hearing including treatment of persons with hearing defects. [NIH] Audiology: The study of hearing and hearing impairment. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress.
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Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] 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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in
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the treatment of gallstones. [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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the
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heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It
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is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through
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enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] CDC2: It is crucial for entry into mitosis of eukaryotic cells. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [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 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
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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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetomacrogol: Non-ionic surfactant of the polyethylene glycol family. It is used as a solubilizer and emulsifying agent in foods, cosmetics, and pharmaceuticals, often as an ointment base, and also as a research tool. [NIH] Chancroid: Acute, localized autoinoculable infectious disease usually acquired through sexual contact. Caused by Haemophilus ducreyi, it occurs endemically almost worldwide, especially in tropical and subtropical countries and more commonly in seaports and urban
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areas than in rural areas. [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] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] 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] Choristoma: A mass of histologically normal tissue present in an abnormal location. [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]
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Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonal Deletion: Removal, via cell death, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
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[NIH]
Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Coliphages: Viruses whose host is Escherichia coli. [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, 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] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colposcopy: The examination, therapy or surgery of the cervix and vagina by means of a specially designed endoscope introduced vaginally. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin
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system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a
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treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] 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] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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
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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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Stroma: The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Cosmids: Plasmids containing at least one cos (cohesive-end site) of phage lambda. They are used as cloning vehicles for the study of aberrant eukaryotic structural genes and also as genetic vectors for introducing the nucleic acid of transforming viruses into cultured cells. [NIH]
Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH]
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Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Coxsackieviruses: A heterogeneous group of the genus enterovirus found in association with various diseases in man and other animals. Two groups (A and B) have been identified with a number of serotypes in each. The name is derived from a village in New York State where the virus was first identified. [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] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Croup: A condition characterized by resonant barking cough, hoarseness and persistant stridor and caused by allergy, foreign body, infection, or neoplasm. It occurs chiefly in infants and children. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions). [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] 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] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU]
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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] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] 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] 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] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [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. [NIH]
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Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Assistants: Individuals who assist the dentist or the dental hygienist. [NIH] Dental Calculus: Abnormal concretion or calcified deposit that forms around the teeth or dental prostheses. [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 Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental Materials: Materials used in the production of dental bases, restorations, impressions, prostheses, etc. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH]
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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] Diagnosis, Differential: Determination of which one of two or more diseases or conditions a patient is suffering from by systematically comparing and contrasting results of diagnostic measures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] 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] Diphosphates: Inorganic salts of phosphoric acid that contain two phosphate groups. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH]
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Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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] Douching: A jet or current of water, sometimes a dissolved medicating or cleansing agent, applied to a body part, organ or cavity for medicinal or hygienic purposes. [EU] 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] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [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]
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Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [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] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Echinacea: A genus of perennial herbs used topically and internally. It contains echinacoside, glycosides, inulin, isobutyl amides, resin, and sesquiterpenes. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]
Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH]
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Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emollient: Softening or soothing; called also malactic. [EU] 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] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endodontics: A dental specialty concerned with the maintenance of the dental pulp in a state of health and the treatment of the pulp cavity (pulp chamber and pulp canal). [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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]
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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [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]
Epstein: Failure of the upper eyelid to move downward on downward movement of the eye, occurring in premature and nervous infants. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may
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result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warm-blooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce diarrhea and pyogenic infections. [NIH]
Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eucalyptus: A genus of Australian trees of the Myrtaceae family that yields gums, oils, and resins which are used as flavoring agents, astringents, and aromatics, and formerly to treat diarrhea, asthma, bronchitis, and respiratory tract infections. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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]
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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Nerve Diseases: Diseases of the facial nerve or nuclei. Pontine disorders may affect the facial nuclei or nerve fascicle. The nerve may be involved intracranially, along its course through the petrous portion of the temporal bone, or along its extracranial course. Clinical manifestations include facial muscle weakness, loss of taste from the anterior tongue, hyperacusis, and decreased lacrimation. [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] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but
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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] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]
Flexor: Muscles which flex a joint. [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] Fold: A plication or doubling of various parts of the body. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [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] Galactans: Polysaccharides composed of repeating galactose units. They can consist of branched or unbranched chains in any linkages. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH]
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Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] 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] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] 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
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such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic Vectors: Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from plasmids, bacteriophages or viruses. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition. [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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gingival Recession: The exposure of root surface by an apical shift in the position of the gingiva. [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] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [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] Glossalgia: Painful sensations in the tongue, including a sensation of burning. [NIH] Glossitis: Inflammation of the tongue. [NIH] Glossodynia: Pain in the tongue; glossalgia. [EU] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste
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afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of health-
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related institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Annulare: Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hand, Foot and Mouth Disease: A mild, highly infectious viral disease of children, characterized by vesicular lesions in the mouth and on the hands and feet. It is caused by coxsackieviruses A. [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
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response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Helminthiasis: Infestation with parasitic worms of the helminth class. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] 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] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH]
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Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatitis D: Hepatitis caused by the hepatitis delta virus in association with hepatitis B. It is endemic in some European countries and is seen in drug users, hemophiliacs, and polytransfused persons. [NIH] Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. Officially this is classified as a subviral satellite RNA. [NIH] Hepatocyte: A liver cell. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Genitalis: Herpes simplex of the genitals. [NIH] Herpes Simplex Encephalitis: An inflammatory disease of the skin or mucous membrane characterized by the formation of clusters of small vesicles. [NIH] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Herpesviridae: A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. There are three subfamilies based on biological characteristics: Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae. [NIH] Herpesvirus Vaccines: Vaccines or candidate vaccines used to prevent infection by any virus from the family Herpesviridae. [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]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of
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the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-cell: A cell whose metabolism is used for the growth and reproduction of a virus. [NIH] Housekeeping: The care and management of property. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or
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T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] 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] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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] Hypodermic: Applied or administered beneath the skin. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [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] Hysteroscopy: Endoscopic examination, therapy or surgery of the interior of the uterus. [NIH]
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
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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] Idoxuridine: An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent, particularly in the treatment of herpes simplex keratitis. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [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] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] 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]
Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] 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]
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Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]
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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]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [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] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [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] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Integumentary: Pertaining to or composed of skin. [EU] 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]
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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-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well 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] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial tumors: Tumors that occur in the brain. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH]
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Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Iridocyclitis: Acute or chronic inflammation of the iris and ciliary body characterized by exudates into the anterior chamber, discoloration of the iris, and constricted, sluggish pupil. Symptoms include radiating pain, photophobia, lacrimation, and interference with vision. [NIH]
Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented
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epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isosporiasis: Infection with parasitic protozoa of the genus Isospora, producing intestinal disease. It is caused by ingestion of oocysts and can produce tissue cysts. [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] 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] Keratitis: Inflammation of the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratomileusis: Carving of the cornea to reshape it. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [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] Lacrimal: Pertaining to the tears. [EU] Lacrimal Apparatus: The tear-forming and tear-conducting system which includes the lacrimal glands, eyelid margins, conjunctival sac, and the tear drainage system. [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]
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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] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [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] 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] Linkages: 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH]
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Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to 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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] 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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The
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color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lyme Disease: An infectious disease caused by a spirochete, Borrelia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinis in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut. [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]
Lymphadenitis: Inflammation of the lymph nodes. [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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphogranuloma Venereum: Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. but is more widespread in developing countries. It is distinguished from granuloma venereum (granuloma inguinale), which is caused by Calymmatobacterium granulomatis. [NIH]
Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU]
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Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant meningioma: A rare, quickly growing tumor that occurs in the membranes that cover and protect the brain and spinal cord (meninges). [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mandibular Nerve: A branch of the trigeminal (5th cranial) nerve. The mandibular nerve carries motor fibers to the muscles of mastication and sensory fibers to the teeth and gingivae, the face in the region of the mandible, and parts of the dura. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] 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]
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Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [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] Meningoencephalitis: An inflammatory process involving the brain (encephalitis) and meninges (meningitis), most often produced by pathogenic organisms which invade the central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions. [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] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU]
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Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbicide: Any substance (gels, creams, suppositories, etc.) that can reduce transmission of sexually transmitted infections. [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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsporidiosis: Infections with protozoa of the phylum Microspora. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [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] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
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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 Motors: Protein based machines that are involved in or cause movement such as the rotary devices (flagellar motor and the F1 ATPase) or the devices whose movement is directed along cytoskeletal filaments (myosin, kinesin and dynein motor families). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]
Monophosphate: So called second messenger for neurotransmitters and hormones. [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] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH]
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Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutilation: Injuries to the body. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
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] Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasolacrimal: Pertaining to the nose and lacrimal apparatus. [EU] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [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
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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] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neisseria: A genus of gram-negative, aerobic, coccoid bacteria whose organisms are part of the normal flora of the oropharynx, nasopharynx, and genitourinary tract. Some species are primary pathogens for humans. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Hepatitis: Irritation of the liver with no known cause. Occurs in newborn babies. Symptoms include jaundice and liver cell changes. [NIH] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] 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] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH]
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Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] 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] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [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] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neurotrophins: A nerve growth factor. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH]
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Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [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] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Nonoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Nonoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide, formulated primarily as a component of vaginal foams and creams. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Localization Signal: Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at nuclear pores. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] 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] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The
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prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odynophagia: A painful condition of the esophagus. [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] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Olfaction Disorders: Loss of or impaired ability to smell. This may be caused by olfactory nerve diseases; paranasal sinus diseases; viral respiratory tract infections; craniocerebral trauma; smoking; and other conditions. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to
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form rhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Oropharynx: Oral part of the pharynx. [NIH] Orthodontics: A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion). [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]
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Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [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] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Ototoxic: Having a deleterious effect upon the eighth nerve, or upon the organs of hearing and balance. [EU] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which
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may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Parapoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirinae, which infect ungulates and may infect humans. Orf virus is the type species. [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] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
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Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Pemphigoid, Bullous: A chronic and relatively benign subepidermal blistering disease usually of the elderly and without histopathologic acantholysis. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] 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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perianal: Located around the anus. [EU] 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]
Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Permissiveness: The attitude that grants freedom of expression and activity to another individual, but not necessarily with sanction or approval. [NIH]
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Peroral: Performed through or administered through the mouth. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [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] Pharyngitis: Inflammation of the throat. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously
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concentrated light rays or specific wavelengths. [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] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] 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] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive
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transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polioviruses: Species of enterovirus causing acute infection in humans and leading to nervous system damage in a minority of cases. Humans are the only natural host, but infection can also occur in non-human primates and experimentally in rodents. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] 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] 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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polytetrafluoroethylene: Homopolymer of tetrafluoroethylene. Nonflammable, tough, inert plastic tubing or sheeting; used to line vessels, insulate, protect or lubricate apparatus; also as filter, coating for surgical implants or as prosthetic material. Synonyms: Fluoroflex; Fluoroplast; Ftoroplast; Halon; Polyfene; PTFE; Tetron. [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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH]
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Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Poxviridae: A family of double-stranded DNA viruses infecting mammals (including humans), birds and insects. There are two subfamilies: Chordopoxvirinae, poxviruses of vertebrates, and Entomopoxvirinae, poxviruses of insects. [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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] 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] Primary tumor: The original tumor. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or
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severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [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] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]
Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Transport: The process of moving proteins from one cellular compartment
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(including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan Infections: Infections with unicellular organisms of the subkingdom Protozoa. [NIH]
Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudorabies: A highly contagious herpesvirus infection affecting the central nervous system of swine, cattle, dogs, cats, rats, and other animals. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychosexual: Pertaining to the mental aspects of sex. [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
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and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [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] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] 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] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire.
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Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] 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] Rape: Unlawful sexual intercourse without consent of the victim. [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] 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, Cytokine: Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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
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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]
Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [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] Resected: Surgical removal of part of an organ. [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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The
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outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH]
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Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rubella Virus: The type (and only) species of Rubivirus causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis. [NIH] Rural Health: The status of health in rural populations. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Safe Sex: Sex behavior that prevents or decreases the spread of sexually transmitted diseases or pregnancy. [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] 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]
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Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Schizogony: Reproduction by fission. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [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] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Mutilation: The act of injuring one's own body to the extent of cutting off or permanently destroying a limb or other essential part of a body. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains
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spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] 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] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Behavior: Sexual activities of humans. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Counseling: Advice and support given to individuals to help them understand and resolve their sexual adjustment problems. It excludes treatment for psychosexual disorders or psychosexual dysfunction. [NIH] Sexual Abstinence: Refraining from sexual intercourse. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [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
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circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH]
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Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Specimen Handling: Procedures for collecting, preserving, and transporting of specimens sufficiently stable to provide accurate and precise results suitable for clinical interpretation. [NIH]
Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [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] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and
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cryptogamic plants. [NIH] Sporozoite: In the sporozoa the product of schizogony of the zygote. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] 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]
Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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
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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]
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] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [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] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH]
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Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [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] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] 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] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Taste Disorders: Conditions characterized by an alteration in gustatory function or perception. Taste disorders are frequently associated with olfaction disorders. Additional potential etiologies include metabolic diseases; drug toxicity; and taste pathway disorders
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(e.g., taste bud diseases; facial nerve diseases; glossopharyngeal nerve diseases; and brain stem diseases). [NIH] Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [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] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] 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]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and
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multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tin ethyl etiopurpurin: An anticancer drug that is also used in cancer prevention. It belongs to the family of drugs called photosensitizing agents. Also called SnET2. [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] Tome: A zone produced by a number of irregular spaces contained in the outermost layer of denture of the root of a tooth. [NIH] 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] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Toothache: Pain in the adjacent areas of the teeth. [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] 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] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [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
396 Herpes Simplex
branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent
Dictionary 397
or not functional. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigeminal Ganglion: The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves. [NIH] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] 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] Tungsten: A metallic element with the atomic symbol W, atomic number 74, and atomic weight 183.85. It is used in many manufacturing applications, including increasing the hardness, toughness, and tensile strength of steel; manufacture of filaments for incandescent light bulbs; and in contact points for automotive and electrical apparatus. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] 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] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH]
398 Herpes Simplex
Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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]
Urethritis: Inflammation of the urethra. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [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] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH]
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Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia virus and varicella zoster virus. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca
400 Herpes Simplex
alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins. [NIH] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Latency: The ability of a pathogenic virus to lie dormant within a cell (latent infection). In eukaryotes, subsequent activation and viral replication is thought to be caused by extracellular stimulation of cellular transcription factors. Latency in bacteriophage is maintained by the expression of virally encoded repressors. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Virus Shedding: The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (disease transmission, vertical). [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH]
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Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [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] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [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] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and
402 Herpes Simplex
transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
403
INDEX A Abdominal, 261, 315, 327, 338, 346, 358, 373, 375, 397 Abdominal Pain, 261, 315, 346, 397 Aberrant, 88, 315, 334 Acantholysis, 315, 375 Acceptor, 315, 361, 373, 394, 396 Acetylgalactosamine, 315, 348 Acetylglucosamine, 315, 348 Acne, 195, 315 Aconitine, 154, 315 Acoustic, 264, 315 Acute Disease, 217, 315 Acute lymphoblastic leukemia, 261, 315 Acute lymphocytic leukemia, 315 Acute myeloid leukemia, 315, 380 Adaptability, 315, 327, 328 Adaptation, 315, 377 Adenine, 316 Adenocarcinoma, 316, 370 Adenosine, 167, 207, 316, 353, 359, 376 Adenovirus, 14, 29, 34, 59, 80, 151, 194, 217, 218, 222, 259, 316 Adenylate Cyclase, 207, 316, 329, 345 Adjustment, 315, 316, 388 Adjuvant, 15, 28, 37, 67, 90, 193, 200, 206, 217, 235, 316, 318 Adjuvant Therapy, 206, 316 Adolescence, 136, 261, 316 Adoptive Transfer, 36, 316 Adrenal Cortex, 316, 334, 379 Adrenal Medulla, 316, 342, 370 Adrenergic, 27, 44, 316, 342, 393 Adverse Effect, 185, 316, 340, 389 Aerobic, 316, 365, 367, 368 Afferent, 172, 246, 316, 344 Affinity, 23, 31, 50, 53, 95, 173, 316, 317, 322, 369, 389 Agar, 317, 377 Ageing, 211, 317 Agonist, 35, 317 Algorithms, 317, 324 Alimentary, 317, 374 Alkaline, 82, 317, 326 Alkaloid, 315, 317, 326 Alkylating Agents, 317, 398 Alleles, 51, 93, 317 Allergen, 317, 388
Allergic Rhinitis, 245, 317 Allogeneic, 151, 317, 349, 350 Allografts, 247, 317 Alpha Particles, 317, 382 Alphavirus, 15, 317, 389 Alternative medicine, 278, 317 Alum, 200, 317 Aluminum, 200, 317, 318 Aluminum Hydroxide, 200, 318 Alveoli, 318, 337 Amber, 318, 355 Amine, 318, 352 Amino Acid Motifs, 318, 333 Amino Acid Sequence, 199, 318, 320, 333, 346, 370 Amino Acids, 167, 192, 193, 202, 227, 238, 318, 333, 346, 371, 375, 378, 381, 385, 396, 398 Amino-terminal, 152, 318 Amplification, 6, 34, 63, 67, 90, 91, 199, 261, 318 Ampulla, 318, 329 Anaerobic, 318, 343, 367, 391, 399 Anaesthesia, 318, 355 Anal, 188, 216, 318, 342, 345 Analog, 187, 233, 315, 318, 345, 354 Analogous, 32, 318, 378, 396 Anaphylatoxins, 318, 332 Anaplasia, 319 Anatomical, 13, 220, 319, 322, 338, 355 Androgens, 316, 319, 334 Anemia, 252, 261, 319, 326 Anergic, 9, 319 Anergy, 319 Anesthesia, 204, 319 Anesthetics, 250, 319, 342 Aneurysm, 319, 399 Angiogenesis, 93, 319, 363 Animal model, 7, 8, 16, 21, 29, 33, 34, 48, 54, 193, 207, 213, 224, 226, 255, 319 Anions, 319, 358 Annealing, 319, 378 Anode, 204, 319 Anogenital, 181, 182, 319, 349 Anomalies, 260, 319, 372, 394 Anorexia, 252, 319, 346 Antagonism, 9, 10, 319 Anterior chamber, 39, 319, 358
404 Herpes Simplex
Anterograde, 58, 64, 319 Antiallergic, 319, 334 Antiangiogenesis, 23, 319 Antibacterial, 149, 320, 390 Antibiotic, 209, 319, 320, 365, 375, 390, 394, 399 Antibody therapy, 90, 320 Anticoagulant, 320, 380 Antifungal, 264, 320 Antigen-Antibody Complex, 320, 332 Antigen-presenting cell, 320, 336 Antihypertensive, 320, 345 Anti-infective, 320, 329 Anti-inflammatory, 151, 161, 320, 322, 327, 334, 348 Anti-Inflammatory Agents, 320, 322, 327, 334 Antimetabolite, 315, 320 Antimicrobial, 110, 111, 160, 162, 164, 204, 216, 251, 255, 320, 337, 380, 394 Antimycotic, 320, 380 Antineoplastic, 253, 258, 317, 320, 334, 365, 395, 399 Antineoplastic Agents, 253, 258, 317, 320, 399 Antioxidant, 243, 320, 373 Antiserum, 320, 323 Antiviral Agents, 4, 18, 102, 192, 210, 321 Anus, 180, 318, 319, 321, 325, 375, 383 Aphthous Stomatitis, 5, 253, 258, 259, 260, 263, 268, 321 Apolipoproteins, 321, 361 Aponeurosis, 321, 346 Aqueous, 148, 158, 203, 216, 321, 323, 336 Arachidonate 12-Lipoxygenase, 321, 361 Arachidonate 15-Lipoxygenase, 321, 361 Arachidonate Lipoxygenases, 321, 361 Arginine, 149, 167, 241, 318, 321, 372, 382 Arrhythmia, 315, 321 Arterial, 214, 321, 327, 329, 333, 353, 380 Arteries, 214, 321, 325, 327, 334, 361, 365, 367, 382 Arterioles, 321, 325, 367 Arthroplasty, 121, 321 Articular, 321, 373 Aspirin, 243, 321 Assay, 31, 43, 45, 46, 53, 64, 67, 68, 69, 70, 72, 98, 108, 115, 117, 199, 219, 228, 322, 354 Asthenia, 319, 322 Astringents, 322, 343 Astrocytes, 20, 322, 347, 369
Astrocytoma, 322, 347 Asymptomatic, 5, 6, 35, 48, 148, 185, 197, 219, 226, 235, 322, 351 Atopic, 102, 148, 322 Atrial, 322, 333, 396 Atrioventricular, 322, 334 Atrium, 322, 334, 396, 399 Atrophy, 315, 322, 343 Attenuated, 61, 65, 82, 105, 193, 197, 201, 215, 216, 242, 322, 386 Atypical, 250, 258, 263, 265, 322, 356 Audiologist, 261, 322 Audiology, 260, 322 Auditory, 260, 322 Autoantibodies, 322, 337 Autoimmune disease, 229, 322 Autologous, 108, 135, 322, 350 Autologous bone marrow transplantation, 108, 322, 350 Autonomic, 47, 322, 347, 370, 375 Autonomic Nervous System, 322, 375 Autosuggestion, 323, 353 Avidity, 70, 81, 323 Axonal, 57, 62, 65, 87, 213, 323 Axons, 64, 196, 323, 337, 357, 368, 372, 379, 385 Axotomy, 11, 323 B Bacterial Infections, 256, 257, 259, 264, 323, 328 Bacteriophage, 41, 323, 377, 396, 400 Bacterium, 58, 205, 233, 323, 350, 395 Basal Ganglia, 323, 346, 347 Base, 6, 61, 70, 82, 195, 203, 316, 323, 328, 336, 337, 346, 359, 378, 394 Basement Membrane, 323, 344 Benign, 21, 197, 201, 229, 257, 262, 323, 346, 349, 350, 368, 370, 373, 375, 383, 386 Benign tumor, 21, 323 Bilateral, 104, 323, 343, 385 Bile, 257, 323, 324, 345, 346, 352, 359, 361, 391 Bile Acids, 323, 346, 391 Bile Acids and Salts, 323 Bile Ducts, 324 Biliary, 265, 324, 329 Binding Sites, 39, 50, 53, 115, 324 Bioavailability, 54, 87, 149, 187, 324 Biochemical reactions, 324, 394 Biological response modifier, 324, 356 Biological therapy, 324, 349 Biological Transport, 324, 338
Index 405
Bioluminescence, 87, 152, 324 Biopsy, 227, 261, 266, 311, 324 Biosynthesis, 324, 345, 372 Biotechnology, 16, 60, 100, 124, 217, 255, 278, 289, 324 Biotin, 324, 371 Biphasic, 106, 324 Bladder, 150, 245, 246, 324, 369, 380, 398 Blepharitis, 11, 268, 324 Blister, 4, 310, 324, 375 Blood Coagulation, 324, 326, 394 Blood pressure, 320, 324, 326, 353, 366, 382, 389 Blot, 325, 371 Body Fluids, 325, 340, 389 Bone Marrow, 108, 119, 143, 208, 315, 322, 325, 350, 354, 362, 366, 380, 390, 392 Bone Marrow Transplantation, 108, 143, 325 Bone scan, 325, 386 Bowel, 245, 252, 261, 268, 318, 325, 338, 356, 357, 397 Bowel Movement, 261, 325, 338 Brachytherapy, 325, 357, 359, 382, 401 Brain Stem, 325, 394, 397 Branch, 75, 150, 154, 307, 325, 341, 350, 362, 363, 374, 381, 390, 394 Bronchi, 325, 342, 396 Bronchial, 245, 325, 352 Bronchitis, 325, 343 Buccal, 325, 362, 392 Bullous, 264, 325, 337 Burning Mouth Syndrome, 253, 258, 263, 325 Burns, 121, 211, 245, 259, 325 Burns, Electric, 325 Bypass, 9, 325 C Cadmium, 193, 325, 326 Cadmium Poisoning, 326 Calcium, 65, 106, 122, 326, 330, 331, 363, 389 Callus, 326, 359 Candidiasis, 250, 252, 253, 256, 258, 259, 260, 261, 262, 263, 267, 268, 269, 279, 326 Candidosis, 250, 259, 326 Capsaicin, 66, 245, 326 Capsid, 13, 25, 42, 64, 65, 73, 77, 93, 98, 100, 118, 215, 225, 326, 370, 400 Capsules, 326, 339 Carbohydrate, 218, 238, 326, 334, 348, 378, 388
Carcinogenic, 317, 326, 356, 371, 380, 391 Carcinogens, 326, 330 Carcinoma, 259, 326, 370 Cardia, 102, 326 Cardiac, 214, 326, 334, 340, 341, 342, 367, 384, 391 Cardiovascular, 104, 326 Cardiovascular disease, 104, 326 Carotene, 326, 385 Case report, 4, 114, 116, 117, 140, 327, 330, 344 Case series, 327, 330 Caspase, 75, 104, 112, 192, 327 Catecholamines, 44, 45, 316, 327 Catheterization, 327, 358 Cathode, 204, 319, 327, 340 Cations, 327, 358 Caudal, 327, 338, 353, 378 Causal, 26, 327, 342, 388 CDC2, 66, 75, 95, 97, 327 Celecoxib, 243, 327 Celiac Artery, 327, 350 Celiac Disease, 259, 327 Cell Count, 101, 327 Cell Cycle, 75, 78, 89, 204, 205, 242, 327, 380, 381 Cell Death, 20, 75, 112, 145, 205, 222, 321, 327, 330, 347, 368 Cell Differentiation, 327, 389 Cell Division, 246, 323, 327, 328, 335, 349, 364, 365, 377, 380, 387 Cell Lineage, 44, 327 Cell membrane, 236, 243, 324, 328, 337, 346, 364, 376, 401 Cell proliferation, 54, 57, 328, 357, 371, 389 Cell Survival, 71, 91, 164, 223, 328, 349 Cell Transplantation, 328, 350 Cellulose, 328, 345, 377 Central Nervous System Infections, 84, 328, 350 Cerebral, 118, 323, 325, 328, 342, 343, 347, 394, 397 Cerebral hemispheres, 323, 325, 328, 347 Cerebrospinal, 64, 67, 69, 84, 98, 107, 132, 138, 179, 184, 328 Cerebrospinal fluid, 84, 107, 132, 138, 179, 184, 328 Cerebrovascular, 326, 328 Cerebrum, 328, 397 Cervical, 29, 107, 109, 165, 174, 199, 276, 328, 386 Cervix, 46, 199, 202, 312, 328, 331
406 Herpes Simplex
Cetomacrogol, 6, 328 Chancroid, 253, 328 Character, 329, 336, 348 Cheilitis, 253, 258, 259, 262, 264, 329 Chemokines, 32, 36, 85, 174, 329 Chemotactic Factors, 329, 332 Chemotherapy, 50, 89, 110, 116, 159, 160, 162, 164, 194, 210, 253, 254, 255, 258, 316, 329 Chickenpox, 186, 260, 263, 329 Chlamydia, 37, 104, 107, 250, 251, 252, 253, 329, 349, 362 Chlorhexidine, 256, 329 Chlorophyll, 329, 345 Cholera, 207, 329, 388, 399 Cholera Toxin, 207, 329 Cholestasis, 257, 329 Cholesterol, 214, 323, 329, 330, 334, 361, 391 Cholesterol Esters, 329, 361 Chorioretinitis, 329, 385 Choristoma, 259, 329 Choroid, 329, 384, 385, 398 Chromatin, 57, 321, 329, 390 Chromium, 32, 330 Chromosomal, 19, 20, 257, 318, 329, 330, 377, 385 Chromosome, 11, 50, 65, 330, 360, 387, 396 Chronic lymphocytic leukemia, 129, 330 Chylomicrons, 330, 361 Cicatricial, 264, 330 Cidofovir, 61, 181, 183, 330 Ciliary, 330, 358, 398 Ciliary Body, 330, 358, 398 Circulatory system, 204, 330, 341 CIS, 66, 330, 385 Citric Acid, 18, 330 Citrus, 330 Clamp, 41, 330 Clear cell carcinoma, 330, 337 Clinical Medicine, 4, 17, 330, 379 Clinical study, 35, 330 Clonal Deletion, 207, 330 Clone, 207, 331 Cloning, 51, 228, 236, 245, 324, 331, 334 Cofactor, 31, 40, 63, 141, 174, 272, 331, 380, 394 Cognition, 21, 331 Cognitive restructuring, 331, 392 Cohort Studies, 331, 342 Coliphages, 323, 331 Colitis, 261, 331
Collagen, 323, 331, 344, 349, 363, 377, 380 Colloidal, 331, 340 Colorectal, 34, 331 Colorectal Cancer, 34, 331 Colposcopy, 107, 331 Combination Therapy, 206, 331 Combinatorial, 228, 331 Complement, 51, 68, 77, 80, 127, 162, 230, 318, 331, 332, 346, 363, 388 Complementary and alternative medicine, 157, 170, 332 Complementary medicine, 157, 332 Complementation, 29, 50, 332 Computational Biology, 289, 332 Computed tomography, 332, 386 Computerized axial tomography, 332, 386 Conception, 332, 333, 344, 391 Concomitant, 184, 204, 332 Concretion, 332, 337 Condoms, 29, 47, 276, 296, 297, 312, 332 Condyloma, 257, 265, 332 Cones, 333, 385 Congestion, 333, 342 Conjugated, 201, 323, 333, 335 Conjunctiva, 33, 216, 312, 332, 333, 356, 359, 397 Conjunctivitis, 268, 332, 333 Connective Tissue, 325, 331, 332, 333, 334, 344, 345, 362, 364, 385, 386 Connexins, 333, 346 Consciousness, 333, 336, 339, 384 Consensus Sequence, 223, 318, 333 Conserved Sequence, 318, 333 Constitutional, 333, 385 Constriction, 333, 359, 399 Consumption, 333, 337, 338, 346, 384 Contamination, 19, 333, 351, 386 Contraception, 253, 333 Contraindications, ii, 333 Controlled study, 161, 185, 333 Cor, 33, 121, 333 Cornea, 8, 33, 37, 43, 58, 87, 94, 98, 216, 319, 334, 359, 387, 398, 402 Corneal Stroma, 47, 334 Corneal Transplantation, 33, 334 Coronary, 214, 326, 334, 365, 367 Coronary Arteriosclerosis, 334, 367 Coronary heart disease, 326, 334 Coronary Thrombosis, 334, 365, 367 Cortex, 334, 341, 343, 373 Cortical, 20, 334, 387 Corticosteroid, 104, 160, 277, 334
Index 407
Cosmids, 111, 334 Cowpox, 334, 335, 398 Cowpox Virus, 334, 335, 398 Coxsackieviruses, 335, 349 Cranial, 335, 344, 347, 350, 363, 368, 372, 375, 397 Craniocerebral Trauma, 335, 350, 371 Crossing-over, 335, 383 Cross-Sectional Studies, 335, 342 Croup, 232, 335 Cryptosporidiosis, 252, 335 Cultured cell line, 58, 335 Cultured cells, 13, 15, 19, 193, 334, 335 Curative, 335, 394 Cutaneous, 45, 71, 79, 94, 109, 111, 197, 203, 204, 326, 335, 362, 398, 399 Cyclic, 207, 316, 335, 345, 387 Cyst, 260, 335 Cysteine, 77, 227, 229, 242, 329, 335 Cystine, 335 Cytochrome, 145, 335 Cytokine, 8, 9, 12, 23, 24, 32, 33, 39, 40, 45, 67, 68, 130, 200, 336, 357 Cytomegalovirus Infections, 214, 336, 345 Cytoplasm, 62, 122, 321, 328, 329, 336, 349, 366, 385 Cytosine, 59, 181, 336 Cytotoxic chemotherapy, 266, 336 Cytotoxicity, 31, 149, 336 D Databases, Bibliographic, 289, 336 Decarboxylation, 336, 352, 372, 382 Defense Mechanisms, 77, 244, 336 Degenerative, 336, 347, 351, 385 Dehydration, 329, 336 Delavirdine, 336, 370 Deletion, 25, 61, 63, 68, 80, 83, 109, 193, 194, 197, 224, 229, 242, 321, 330, 336 Dementia, 6, 258, 336 Denaturation, 336, 378 Dendrites, 336, 337, 369 Dendritic, 11, 30, 81, 109, 140, 141, 336, 364, 385 Dendritic cell, 30, 109, 140, 141, 336 Density, 214, 337, 361, 371, 378 Dental Assistants, 263, 337 Dental Calculus, 257, 337 Dental Care, 267, 337, 375 Dental Hygienists, 4, 5, 263, 337 Dental Materials, 249, 337 Dentate Gyrus, 337, 352 Dentifrices, 318, 337
Dentists, 3, 249, 263, 337 Dentition, 256, 337 Deoxyribonucleotides, 193, 337 Depigmentation, 337, 400 Depolarization, 337, 389 Deprivation, 193, 337 Dermal, 69, 196, 204, 337, 360 Dermatitis, 102, 148, 264, 337, 340 Dermatitis Herpetiformis, 264, 337 DES, 53, 318, 337 Detergents, 337, 370 Developed Countries, 199, 337 Developing Countries, 52, 212, 338, 362 Diabetes Mellitus, 261, 338, 348, 350 Diagnosis, Differential, 268, 338 Diagnostic procedure, 191, 278, 338, 388 Diaphragm, 338, 377 Diarrhea, 33, 245, 252, 261, 335, 338, 343 Diencephalon, 338, 353, 394 Diffusion, 20, 111, 324, 338, 356 Digestion, 317, 323, 324, 325, 338, 357, 361, 391, 398 Digestive system, 190, 338, 346, 366 Digestive tract, 338, 389, 391 Dihydrotestosterone, 338, 383 Dilatation, 319, 338, 379, 399 Dilatation, Pathologic, 338, 399 Dilation, 338, 399 Diphosphates, 193, 338 Diploid, 217, 332, 338, 377 Direct, iii, 10, 17, 20, 30, 34, 40, 41, 67, 69, 114, 151, 281, 330, 338, 374, 383, 393 Disease Progression, 185, 338, 400 Disease Transmission, 338, 400 Disease Transmission, Vertical, 338, 400 Dissection, 9, 339 Dissociation, 76, 89, 316, 339, 358 Distal, 48, 323, 339, 340, 346, 379, 381 Docetaxel, 116, 159, 339 Domesticated, 339, 349 Dorsal, 22, 64, 78, 79, 339, 343, 378, 390 Dorsum, 339, 346 Dosage Forms, 242, 339 Dosimetry, 160, 339 Douching, 138, 339 Drive, ii, vi, 9, 147, 204, 210, 253, 256, 257, 258, 261, 262, 263, 264, 266, 268, 297, 339 Dross, 339, 380 Drug Interactions, 283, 339 Drug Resistance, 119, 339 Drug Tolerance, 339, 395 Drug Toxicity, 340, 393
408 Herpes Simplex
Duct, 268, 318, 327, 340, 386 Duodenal Ulcer, 245, 340 Duodenum, 323, 340, 350, 373, 392 Dura mater, 340, 364, 373 Dynein, 73, 118, 340, 366 Dysphagia, 266, 340 Dysplasia, 165, 199, 257, 340 Dystrophic, 340, 342 E Echinacea, 54, 148, 159, 168, 203, 216, 340 Ectopic, 37, 112, 340 Ectopic Pregnancy, 37, 340 Eczema, 108, 257, 309, 340 Edema, 246, 310, 340 Effector, 25, 44, 85, 102, 245, 246, 331, 340, 369 Effector cell, 245, 340, 369 Ejaculation, 340, 387 Elasticity, 211, 334, 340 Electrode, 195, 203, 319, 327, 340 Electrolyte, 334, 340, 365, 389 Electrons, 320, 323, 327, 340, 358, 373, 382, 383 Electrophoresis, 31, 340 Embryo, 327, 328, 340, 355, 378 Emergency Medicine, 253, 341 Emergency Treatment, 263, 341 Emollient, 341, 348, 371 Encephalitis, Viral, 341 Endemic, 50, 329, 341, 351, 390 Endocarditis, 326, 341 Endocrine Glands, 341 Endocrine System, 341, 369 Endodontics, 267, 341 Endonucleases, 22, 231, 341 Endoscope, 331, 341 Endothelial cell, 12, 341, 394 Endotoxin, 341, 397 Enhancer, 27, 57, 71, 218, 225, 341 Enterovirus, 335, 341, 378 Entorhinal Cortex, 341, 352 Environmental Health, 288, 290, 341 Enzymatic, 53, 202, 326, 327, 332, 342, 352, 378, 385 Enzyme Inhibitors, 244, 342 Enzyme-Linked Immunosorbent Assay, 67, 68, 342 Epidemic, 58, 74, 212, 235, 266, 294, 342, 390 Epidemiologic Studies, 199, 342 Epidemiological, 31, 199, 342, 344
Epidermal, 62, 87, 101, 154, 196, 216, 266, 342, 360, 364, 399 Epidermis, 315, 324, 342, 360, 375, 382 Epidermoid carcinoma, 342, 391 Epidermolysis Bullosa, 264, 342 Epinephrine, 43, 82, 316, 342, 370, 397 Epithelial Cells, 31, 122, 230, 329, 342 Epithelial ovarian cancer, 142, 342 Epithelium, 24, 180, 235, 323, 333, 342, 358, 373, 402 Epitope, 10, 28, 81, 107, 202, 228, 235, 342 Erythema, 114, 211, 259, 260, 263, 266, 268, 310, 342, 343, 393 Erythema Multiforme, 259, 263, 266, 268, 343 Erythema Nodosum, 266, 343 Erythrocytes, 319, 325, 343, 388 Escalation, 58, 61, 343 Escherichia, 90, 206, 207, 261, 331, 343, 346, 350 Escherichia coli, 90, 206, 207, 261, 331, 343, 346, 350 Esophageal, 141, 266, 343, 346 Esophagitis, 266, 343, 346 Esophagus, 267, 338, 343, 346, 361, 371, 376, 383, 392 Estrogen, 21, 343 Estrogen receptor, 21, 343 Ether, 18, 31, 343 Eucalyptus, 158, 168, 343 Eukaryotic Cells, 220, 222, 240, 327, 343, 355, 372, 397 Evoke, 343, 391 Exfoliation, 343, 368 Exhaustion, 319, 343 Exogenous, 62, 75, 245, 340, 343 Extensor, 343, 381, 400 External-beam radiation, 343, 359, 382, 401 Extracellular, 9, 12, 53, 229, 231, 322, 333, 343, 344, 363, 369, 381, 389, 400 Extracellular Matrix, 53, 333, 344, 363 Extracellular Matrix Proteins, 344, 363 Extracellular Space, 9, 344 Extraction, 69, 218, 344 Eye Infections, 180, 316, 344 F Facial, 50, 115, 130, 143, 160, 260, 344, 374, 394 Facial Nerve, 344, 374, 394 Facial Nerve Diseases, 344, 394 Family Planning, 29, 289, 344
Index 409
Fat, 323, 325, 326, 333, 334, 344, 361, 390, 393 Fatal Outcome, 198, 344 Fatty acids, 212, 344, 348, 361 Febrile, 26, 148, 344 Fetus, 344, 354, 398 Fibroblasts, 80, 123, 131, 145, 344, 357 Fibrosis, 257, 344, 386 Fixation, 344, 388 Flavoring Agents, 343, 345 Flexor, 343, 345, 360 Fluorescence, 118, 345 Fold, 19, 46, 187, 207, 222, 345, 371 Forskolin, 234, 345 Fungi, 212, 267, 320, 324, 344, 345, 365, 390, 401 Fungus, 221, 326, 345, 367 G Galactans, 161, 345 Gallbladder, 315, 324, 338, 345, 346, 350 Gamma Rays, 345, 382, 383 Ganglion, 22, 33, 64, 79, 346, 385, 397, 402 Gangrenous, 346, 388 Gap Junctions, 150, 333, 346, 393 Gas, 338, 346, 353, 370, 371 Gastric, 102, 245, 318, 327, 339, 346, 352 Gastroenteritis, 346, 386 Gastroenterology, 133, 266, 346 Gastroesophageal Reflux, 266, 346 Gastroesophageal Reflux Disease, 266, 346 Gastrointestinal, 88, 245, 246, 257, 326, 342, 346, 392, 399 Gastrointestinal tract, 88, 246, 346 Gels, 346, 365 Genetic Code, 346, 370 Genetic Engineering, 19, 209, 324, 331, 346 Genetic testing, 347, 378 Genetic Vectors, 334, 347 Genetics, 11, 37, 43, 46, 50, 151, 209, 347 Genitourinary, 67, 245, 298, 347, 368, 398 Genomics, 49, 347 Genotype, 108, 115, 317, 347, 376 Germ Cells, 347, 364, 373, 390, 394 Gestation, 347, 375 Giant Cells, 347, 386 Gingival Recession, 256, 347 Gland, 250, 251, 259, 262, 264, 265, 316, 347, 362, 363, 373, 374, 377, 380, 387, 391, 395 Glial Fibrillary Acidic Protein, 19, 347 Glioblastoma, 19, 61, 112, 210, 347
Glioma, 17, 19, 23, 59, 149, 210, 242, 277, 347 Gliosis, 26, 347 Glossalgia, 347 Glossitis, 260, 262, 347 Glossodynia, 263, 347 Glossopharyngeal Nerve, 347, 394 Glucocorticoid, 209, 348 Glucose, 242, 328, 330, 338, 348, 350, 386 Glucose Intolerance, 338, 348 Glucuronic Acid, 348, 350 Glutamic Acid, 348, 380 Gluten, 259, 327, 348 Glycerol, 18, 348, 376 Glycerophospholipids, 348, 376 Glycogen, 329, 348 Glycosaminoglycans, 32, 60, 236, 344, 348 Glycosidic, 348, 368, 371 Glycosylation, 238, 348 Goats, 348, 372 Gonadal, 348, 391 Gonorrhea, 205, 233, 251, 253, 348 Governing Board, 348, 379 Gp120, 30, 115, 349 Grade, 107, 126, 349 Graft, 121, 214, 317, 349, 352, 355 Graft Rejection, 349, 355 Gram-negative, 329, 343, 349, 367, 368, 399 Gram-positive, 349, 367, 391, 392 Granule, 25, 337, 349, 385 Granulocytes, 349, 389, 401 Granuloma, 266, 349, 362 Granuloma Annulare, 266, 349 Granuloma Inguinale, 349, 362 Growth, 10, 19, 20, 35, 61, 71, 76, 80, 91, 95, 97, 151, 196, 210, 214, 221, 222, 224, 225, 231, 240, 244, 245, 316, 317, 319, 320, 321, 323, 324, 327, 328, 338, 349, 352, 356, 357, 359, 363, 368, 370, 371, 372, 377, 387, 395, 397, 400, 401 Growth factors, 214, 231, 349, 371 Guinea Pigs, 82, 349 H Habitat, 349, 367 Hair follicles, 349, 391, 401 Hand, Foot and Mouth Disease, 259, 261, 264, 268, 349 Haptens, 316, 349 Headache, 245, 310, 350, 356 Headache Disorders, 350 Health Education, 4, 297, 350 Health Services, 298, 350
410 Herpes Simplex
Heart attack, 326, 350 Helminthiasis, 328, 350 Hematogenous, 84, 126, 350 Hematopoietic Stem Cell Transplantation, 105, 151, 350 Heme, 335, 350 Hemoglobin, 319, 343, 350, 360 Hemolytic, 350, 355 Hemorrhage, 126, 335, 350, 376, 382, 392 Heparin, 53, 127, 242, 350 Hepatic, 34, 117, 257, 327, 350 Hepatic Artery, 34, 350 Hepatitis A, 193, 258, 265, 351 Hepatitis C, 116, 133, 159, 351 Hepatitis D, 116, 265, 351 Hepatitis Delta Virus, 351 Hepatocyte, 329, 351 Hepatomegaly, 351, 356 Hepatotoxicity, 257, 351 Hepatovirus, 351 Hereditary, 264, 351, 385 Heredity, 346, 347, 351 Herpes Genitalis, 180, 187, 217, 351 Herpes virus, 4, 11, 27, 38, 45, 50, 53, 124, 179, 180, 188, 192, 193, 195, 205, 209, 213, 215, 216, 218, 219, 221, 225, 229, 232, 233, 237, 238, 241, 242, 243, 272, 276, 277, 351, 399 Herpes Zoster, 115, 195, 252, 257, 261, 262, 263, 267, 351 Herpesviridae, 56, 214, 225, 232, 336, 341, 351 Herpesvirus Vaccines, 239, 351 Heterogeneity, 316, 351 Heterogenic, 351 Heterogenous, 218, 351 Heterotrophic, 345, 351 Hippocampus, 21, 26, 337, 351, 392 Histamine, 93, 318, 352 Histidine, 352 Histiocytosis, 260, 352 Histology, 257, 258, 352 Hoarseness, 335, 352 Homeostasis, 231, 352 Homologous, 11, 120, 239, 317, 333, 335, 352, 366, 381, 387, 388, 393, 396 Hormonal, 297, 322, 334, 352 Hormone, 316, 334, 337, 342, 352, 364, 379, 387, 389, 394, 395 Hormone therapy, 316, 352 Horseradish Peroxidase, 342, 352 Host-cell, 162, 352
Housekeeping, 19, 352 Human papillomavirus, 111, 117, 138, 139, 250, 251, 257, 259, 263, 264, 267, 352 Humoral, 7, 80, 115, 200, 349, 352 Humour, 352 Hybrid, 20, 25, 31, 38, 54, 90, 91, 331, 352, 371 Hybridization, 352, 371 Hybridomas, 352, 357 Hydrogel, 212, 353 Hydrogen, 81, 315, 318, 323, 326, 336, 344, 353, 361, 366, 369, 373, 381, 394 Hydrolysis, 56, 231, 341, 353, 359, 368, 376, 378, 381 Hydrophilic, 337, 353 Hydrophobic, 337, 348, 353, 361 Hygienic, 339, 353 Hyperaemia, 333, 353 Hyperalgesia, 245, 246, 353 Hyperplasia, 257, 260, 265, 353, 360 Hypersensitivity, 317, 353, 388 Hypertension, 326, 350, 353 Hyperthermia, 26, 33, 193, 353 Hypertrophy, 334, 353, 396 Hypodermic, 204, 353 Hypothalamic, 45, 353 Hypothalamus, 40, 323, 338, 353, 377, 394 Hypothermia, 33, 353 Hypoxanthine, 19, 353 Hysteroscopy, 117, 353 I Iatrogenic, 259, 353 Id, 155, 165, 295, 296, 298, 299, 306, 308, 354 Idiopathic, 250, 259, 354, 386 Idoxuridine, 203, 354 Immune adjuvant, 317, 354 Immune function, 44, 45, 354, 355 Immune response, 8, 9, 12, 16, 17, 23, 24, 28, 30, 32, 36, 37, 40, 45, 48, 54, 56, 115, 162, 197, 200, 201, 202, 206, 226, 227, 229, 237, 238, 242, 244, 246, 316, 317, 319, 320, 322, 334, 349, 354, 355, 363, 388, 392, 398, 400 Immune Sera, 354 Immune Tolerance, 207, 354 Immunization, 7, 35, 39, 40, 70, 81, 82, 98, 197, 200, 207, 237, 316, 354, 355, 388 Immunoassay, 67, 89, 108, 342, 354 Immunocompromised, 17, 83, 123, 127, 133, 182, 186, 194, 197, 201, 217, 238, 272, 297, 354
Index 411
Immunodeficiency syndrome, 250, 251, 252, 290, 354 Immunofluorescence, 43, 67, 109, 354 Immunogen, 30, 354 Immunogenic, 9, 37, 200, 201, 202, 226, 354 Immunoglobulin, 5, 35, 66, 69, 70, 82, 87, 89, 95, 113, 198, 200, 228, 320, 354, 366, 388 Immunohistochemistry, 26, 131, 354 Immunologic, 7, 13, 16, 31, 35, 131, 207, 252, 264, 316, 329, 354, 355, 363, 383 Immunologic Factors, 31, 355 Immunosuppressant, 206, 317, 355 Immunosuppressive, 23, 43, 45, 47, 218, 348, 355, 393 Immunosuppressive Agents, 23, 355 Immunosuppressive therapy, 355 Immunotherapy, 32, 109, 244, 316, 324, 355 Impairment, 117, 260, 322, 329, 344, 355, 364 Impetigo, 260, 261, 355 Implant radiation, 355, 357, 359, 382, 401 In situ, 13, 14, 22, 23, 69, 155, 159, 355 In Situ Hybridization, 13, 22, 355 Incision, 355, 358 Incompetence, 346, 355 Incubated, 43, 355 Incubation, 216, 355, 360 Incubation period, 216, 355, 360 Indicative, 184, 253, 355, 374, 399 Induction, 25, 40, 42, 47, 52, 73, 74, 82, 92, 100, 148, 151, 180, 182, 206, 207, 234, 244, 319, 355 Infarction, 356 Infection Control, 241, 356 Infectious Mononucleosis, 257, 260, 265, 356, 366 Infertility, 37, 110, 294, 356 Infiltration, 36, 82, 133, 226, 356, 402 Inflammatory bowel disease, 261, 356 Influenza, 68, 114, 217, 232, 267, 356 Ingestion, 207, 326, 356, 359 Inguinal, 356, 362 Initiation, 8, 13, 34, 37, 39, 42, 43, 96, 196, 356, 396 Initiator, 138, 356, 357 Inoculum, 35, 356 Inorganic, 211, 338, 356, 366 Insight, 8, 11, 12, 22, 25, 40, 42, 44, 58, 356 Integumentary, 260, 356
Interferon, 30, 31, 37, 62, 63, 64, 73, 74, 76, 83, 92, 95, 98, 99, 102, 114, 135, 143, 174, 200, 224, 230, 252, 356, 357, 362 Interferon-alpha, 102, 143, 356, 357 Interleukin-1, 83, 152, 200, 357 Interleukin-12, 83, 200, 357 Interleukin-2, 12, 88, 106, 118, 130, 357 Interleukin-4, 91, 149, 357 Interleukin-6, 33, 84, 92, 357 Interleukins, 355, 357 Intermittent, 182, 357 Internal Medicine, 30, 33, 104, 123, 154, 346, 357 Internal radiation, 357, 359, 382, 401 Interneurons, 26, 357 Interstitial, 94, 111, 325, 344, 357, 359, 364, 401 Intestinal, 327, 329, 335, 341, 357, 359, 363, 400 Intestine, 323, 325, 331, 343, 357, 359, 392 Intoxication, 357, 401 Intracellular Membranes, 357, 364 Intracranial tumors, 23, 357 Intrahepatic, 257, 357 Intramuscular, 357, 374 Intraocular, 345, 358 Intraocular pressure, 345, 358 Intraperitoneal, 142, 243, 358 Intrathecal, 20, 358 Intravascular, 23, 68, 358 Intravenous, 34, 83, 135, 182, 185, 208, 358, 374 Intrinsic, 31, 41, 316, 323, 358 Intubation, 115, 327, 358 Inulin, 340, 358 Invasive, 34, 173, 243, 354, 358, 363 Ion Channels, 322, 358, 369 Ion Exchange, 328, 358 Ionization, 53, 358 Ionizing, 126, 317, 358, 383 Ions, 204, 323, 339, 340, 353, 358 Iontophoresis, 203, 204, 358 Iridocyclitis, 180, 184, 358 Iris, 319, 334, 358, 382, 398 Irradiation, 26, 59, 226, 359, 401 Ischemia, 104, 118, 257, 322, 359 Isosporiasis, 252, 359 J Jaundice, 359, 368 Joint, 321, 345, 359, 393 K Kb, 27, 199, 202, 223, 235, 288, 359
412 Herpes Simplex
Keratitis, 8, 11, 14, 33, 40, 47, 55, 58, 79, 85, 94, 102, 120, 126, 130, 137, 144, 179, 180, 184, 203, 244, 272, 354, 359 Keratoconjunctivitis, 201, 359 Keratomileusis, 155, 159, 359 Keratosis, 260, 315, 359 Kilobase, 60, 62, 63, 77, 82, 94, 97, 197, 359 Kinesin, 58, 103, 359, 366 Kinetic, 13, 17, 31, 41, 127, 173, 358, 359 L Labile, 90, 206, 207, 331, 359 Lacrimal, 344, 359, 367, 372 Lacrimal Apparatus, 359, 367 Large Intestine, 331, 338, 357, 359, 383, 389 Least-Squares Analysis, 360, 384 Lectin, 360, 364 Lentivirus, 20, 29, 360 Lesion, 6, 79, 186, 196, 198, 203, 227, 230, 263, 297, 311, 312, 347, 349, 360, 361, 388, 397 Lethal, 10, 40, 63, 68, 237, 238, 360 Leucine, 43, 152, 360 Leukemia, 50, 54, 125, 265, 315, 360 Leukocytes, 92, 325, 329, 349, 357, 360, 366, 397 Leukoplakia, 250, 251, 259, 263, 267, 272, 279, 360 Library Services, 306, 360 Lichen Planus, 250, 253, 258, 263, 360 Life cycle, 42, 51, 222, 243, 253, 324, 345, 360 Ligament, 360, 380 Ligands, 10, 36, 49, 199, 245, 360 Likelihood Functions, 360, 384 Limbic, 26, 360 Linear Models, 360, 384 Linkages, 345, 348, 350, 360, 368 Lip, 4, 142, 260, 360 Lipid, 18, 139, 212, 214, 221, 227, 231, 232, 245, 321, 348, 361, 373 Lipid Bilayers, 227, 361 Lipid Peroxidation, 361, 373 Lipoprotein, 225, 349, 361, 400 Lipoxygenase, 245, 321, 361 Liver metastases, 55, 92, 361 Liver scan, 361, 386 Liver Transplantation, 133, 361 Logistic Models, 361, 384 Long-Term Potentiation, 21, 361 Low-density lipoprotein, 361 Lower Esophageal Sphincter, 346, 361 Luciferase, 27, 361
Lupus, 257, 260, 362 Lyme Disease, 250, 362 Lymph, 16, 46, 79, 328, 330, 341, 352, 356, 362, 367, 386 Lymph node, 16, 46, 328, 362, 367, 386 Lymphadenitis, 129, 362 Lymphadenopathy, 356, 362 Lymphatic, 356, 362, 364, 386, 390, 394 Lymphatic system, 362, 386, 390, 394 Lymphoblastic, 362 Lymphoblasts, 315, 362 Lymphocyte, 78, 79, 81, 93, 121, 154, 320, 362, 363 Lymphocytic, 129, 362 Lymphogranuloma Venereum, 253, 349, 362 Lymphoid, 49, 229, 320, 362 Lymphokines, 200, 202, 362, 363 Lymphoma, 116, 129, 135, 252, 259, 260, 263, 267, 362, 367 Lymphosarcoma, 44, 362 Lysine, 135, 145, 165, 169, 241, 242, 362 Lysosome, 16, 362 Lytic, 42, 46, 74, 75, 192, 213, 362, 388, 400 M Macrophage, 98, 357, 363 Macrophage Activation, 98, 363 Magnetic Resonance Imaging, 363, 386 Major Histocompatibility Complex, 63, 81, 83, 245, 357, 363 Malabsorption, 327, 363 Malignancy, 199, 363, 374 Malignant, 59, 210, 224, 242, 277, 316, 320, 347, 352, 362, 363, 367, 368, 373, 380, 383, 385, 386 Malignant meningioma, 210, 363 Malignant tumor, 210, 224, 362, 363, 373, 385 Mandibular Nerve, 363, 397 Manifest, 323, 363 Mannans, 345, 363 Mastication, 363, 397 Mastitis, 363, 388 Matrix metalloproteinase, 93, 231, 363 Maxillary, 363, 397 Mediate, 9, 27, 39, 54, 66, 198, 236, 363 Mediator, 72, 73, 76, 80, 84, 129, 228, 229, 236, 357, 363 Medical Records, 364, 385 Medicament, 203, 204, 364, 393 MEDLINE, 289, 364 Meiosis, 364, 366, 393
Index 413
Melanin, 264, 337, 358, 364, 376, 397 Melanocytes, 364, 370 Membrane Fusion, 103, 364 Membrane Proteins, 8, 364 Memory, 47, 48, 174, 310, 319, 336, 361, 364 Meninges, 328, 335, 340, 363, 364 Meningioma, 364 Meningitis, 69, 116, 123, 137, 166, 198, 252, 364, 376 Meningoencephalitis, 127, 364 Mental Disorders, 190, 364, 376, 381 Mental Health, iv, 7, 149, 190, 288, 291, 364, 382 Mentors, 17, 364 Mesenchymal, 20, 364 Metabolic disorder, 264, 364 Metabolite, 187, 364, 376, 379 Metastasis, 12, 363, 365 Metastatic, 12, 244, 365, 387 MI, 91, 96, 192, 312, 365 Mice Minute Virus, 365, 374 Microbe, 216, 365, 395 Microbicide, 18, 46, 85, 130, 365 Microbiological, 18, 365 Microorganism, 331, 365, 374, 401 Microscopy, 13, 22, 43, 48, 64, 98, 154, 323, 352, 365 Microsporidiosis, 252, 365 Microtubules, 359, 365 Migration, 19, 363, 365, 369 Mineralocorticoids, 316, 334, 365 Mitochondria, 365, 372 Mitochondrial Swelling, 365, 368 Mitomycin, 50, 365 Mitosis, 78, 321, 327, 365 Mitotic, 339, 365 Mitotic inhibitors, 339, 365 Modification, 39, 58, 65, 81, 101, 131, 238, 242, 346, 366 Modulator, 43, 244, 366 Molecular Motors, 56, 366 Monitor, 34, 366, 370 Monoclonal, 7, 8, 38, 66, 67, 84, 86, 99, 108, 129, 142, 228, 352, 359, 366, 382, 401 Monoclonal antibodies, 8, 38, 129, 228, 366 Monocytes, 357, 360, 366 Mononuclear, 46, 134, 349, 356, 366, 397 Mononucleosis, 232, 272, 366 Monophosphate, 167, 207, 234, 366 Morphological, 223, 317, 340, 345, 364, 366, 400
Morphology, 131, 363, 366 Motility, 245, 366 Mucinous, 346, 366 Mucins, 366, 386 Mucocutaneous, 181, 186, 188, 197, 198, 226, 366 Mucosa, 7, 35, 40, 48, 49, 128, 203, 212, 216, 257, 264, 268, 327, 362, 366, 392 Mucositis, 108, 260, 366, 394 Mucus, 366, 397 Multivalent, 37, 323, 366 Mutagenesis, 11, 17, 93, 139, 367 Mutagens, 367 Mutilation, 260, 367 Myalgia, 356, 367 Mycobacterium, 140, 261, 367, 397 Mycoplasma, 328, 367 Mycoplasma Infections, 328, 367 Mycosis, 111, 124, 367 Mycosis Fungoides, 111, 124, 367 Myelin, 19, 367, 369 Myocardial infarction, 334, 365, 367 Myocardial Ischemia, 267, 367 Myocardium, 365, 367 Myosin, 366, 367 N Naive, 7, 47, 367 Nasal Mucosa, 356, 367 Nasolacrimal, 268, 367 Nasopharynx, 348, 367, 368 Natural killer cells, 357, 367 Nausea, 339, 346, 367 NCI, 1, 190, 287, 330, 367 Necrolysis, 266, 368 Necrosis, 104, 116, 125, 135, 141, 321, 347, 356, 365, 367, 368, 386 Need, 3, 4, 11, 17, 30, 35, 111, 132, 186, 188, 204, 212, 240, 244, 249, 256, 271, 278, 290, 297, 300, 316, 348, 362, 363, 368, 395 Neisseria, 205, 233, 252, 348, 368 Neonatal, 37, 90, 102, 132, 133, 137, 144, 178, 184, 220, 257, 368 Neonatal Hepatitis, 257, 368 Neonatal period, 257, 368 Neoplasia, 107, 220, 262, 368 Neoplasm, 335, 368, 373, 386, 397 Neoplastic, 20, 192, 199, 201, 221, 222, 252, 264, 319, 352, 362, 368, 371 Nerve Endings, 235, 368 Nerve Fibers, 84, 88, 368 Nerve Growth Factor, 23, 66, 79, 368, 369 Networks, 36, 368
414 Herpes Simplex
Neural, 19, 20, 26, 66, 316, 352, 368 Neuralgia, 103, 166, 368 Neuraminidase, 114, 368, 374 Neuroblastoma, 205, 369 Neuroeffector Junction, 368, 369 Neuroendocrine, 163, 174, 369 Neurogenic, 369, 398 Neuroglia, 347, 369 Neurologic, 178, 184, 185, 210, 347, 369 Neuropathy, 21, 125, 245, 369 Neuropeptides, 39, 45, 369 Neuroretinitis, 369, 385 Neurotoxic, 36, 369 Neurotoxicity, 36, 369 Neurotransmitters, 44, 231, 366, 369, 379 Neurotrophins, 12, 39, 369 Neutralization, 162, 228, 369 Neutrons, 317, 359, 369, 382 Nevirapine, 370 Nevus, 260, 370 Nitrogen, 50, 317, 318, 319, 344, 345, 370 Non-nucleoside, 18, 336, 370 Nonoxynol, 29, 47, 370 Non-small cell lung cancer, 112, 370 Norepinephrine, 316, 370 Nuclear Localization Signal, 50, 370 Nuclear Pore, 77, 370 Nuclei, 145, 213, 227, 235, 246, 317, 340, 344, 347, 363, 365, 369, 370, 372, 381, 386 Nucleocapsid, 58, 239, 370 O Odds Ratio, 6, 370, 384 Odynophagia, 266, 371 Ointments, 339, 371 Olfaction, 371, 393 Olfaction Disorders, 371, 393 Oligonucleotide Probes, 198, 371 Oligosaccharides, 53, 368, 371 Omentum, 350, 371 Oncogenes, 50, 162, 371, 381 Oncogenic, 199, 360, 371 Oncolysis, 23, 92, 222, 224, 242, 371 Oncolytic, 17, 23, 55, 59, 101, 126, 134, 141, 162, 163, 194, 222, 242, 371 Opacity, 337, 371 Open Reading Frames, 75, 360, 371 Operon, 371, 384 Ophthalmic, 15, 141, 283, 371, 397 Opportunistic Infections, 252, 371 Opsin, 371, 385 Optic Chiasm, 353, 372
Optic Nerve, 40, 369, 372, 373, 384, 385, 387 Oral Health, 4, 150, 250, 256, 263, 372 Oral Hygiene, 4, 256, 372 Oral Manifestations, 250, 251, 259, 261, 262, 263, 267, 279, 372 Orbicularis, 124, 161, 372 Orf, 125, 257, 372, 374 Organ Culture, 372, 395 Organ Transplantation, 220, 267, 372 Organelles, 58, 66, 231, 336, 359, 364, 366, 372, 377 Ornithine, 209, 372, 382 Ornithine Decarboxylase, 209, 372 Orofacial, 235, 258, 259, 260, 263, 297, 372 Oropharynx, 311, 368, 372 Orthodontics, 267, 372 Osmosis, 372 Osmotic, 204, 365, 372 Osteoarthritis, 245, 373 Osteogenic sarcoma, 373 Osteomyelitis, 262, 373 Osteosarcoma, 106, 373 Otolaryngologist, 264, 373 Ototoxic, 264, 373 Ovaries, 342, 373, 388 Ovary, 110, 209, 236, 373, 378 Ovum, 347, 360, 373, 379, 402 Oxidation, 315, 320, 321, 335, 361, 373 Oxidative Stress, 243, 373 P Pachymeningitis, 364, 373 Palate, 348, 367, 373, 392 Palliative, 373, 394 Pancreas, 315, 324, 338, 346, 350, 373 Pancreatic, 346, 373 Pancreatic Juice, 346, 373 Papilla, 373 Papillary, 260, 373 Papilloma, 253, 257, 265, 332, 373 Papillomavirus, 209, 259, 373 Paralysis, 24, 374 Paramyxovirus, 232, 374 Parapoxvirus, 125, 374 Parasite, 374, 396 Parasitic, 15, 252, 257, 262, 335, 350, 359, 374, 395 Parasitic Diseases, 262, 374 Parenteral, 30, 207, 257, 374 Parenteral Nutrition, 257, 374 Parietal, 374, 377 Parotid, 252, 347, 374, 386
Index 415
Particle, 9, 223, 374, 396, 400 Parvovirus, 250, 259, 365, 374 Patch, 360, 374, 396 Pathogen, 9, 11, 28, 36, 46, 200, 355, 356, 374 Pathologic, 21, 135, 213, 264, 321, 324, 326, 334, 353, 374, 381, 399 Pathologic Processes, 213, 321, 374 Pathologies, 198, 262, 374 Pathophysiology, 45, 262, 374 Patient Education, 258, 267, 296, 304, 306, 313, 374 Pediatric Dentistry, 256, 261, 375 Pelvic, 37, 251, 375, 380 Pelvic inflammatory disease, 37, 251, 375 Pemphigoid, Bullous, 264, 375 Pemphigus, 253, 258, 260, 264, 315, 375 Penicillin, 319, 375 Penis, 332, 340, 375 Peptide, 9, 15, 28, 50, 81, 82, 85, 201, 202, 221, 226, 235, 238, 329, 375, 378, 380, 381 Perception, 246, 266, 375, 387, 393 Perennial, 340, 375, 396 Perianal, 69, 133, 183, 333, 375 Perinatal, 116, 250, 252, 375 Periodontal disease, 44, 251, 256, 259, 262, 267, 375 Periodontitis, 256, 259, 262, 269, 375 Perioperative, 267, 375 Perioral, 206, 375 Peripheral blood, 46, 134, 350, 357, 375 Peripheral Nervous System, 22, 46, 69, 74, 197, 213, 375, 379, 392 Peritoneal, 358, 375 Peritoneal Cavity, 358, 375 Permissiveness, 162, 375 Peroral, 114, 376 Pharmaceutical Solutions, 339, 376 Pharmacokinetic, 160, 187, 376 Pharmacologic, 150, 319, 376, 395, 398 Pharyngitis, 257, 269, 376, 387 Pharynx, 346, 356, 367, 372, 376 Phenotype, 8, 9, 36, 52, 70, 77, 81, 82, 98, 124, 193, 199, 205, 332, 376 Phenylalanine, 376, 397 Phonophoresis, 358, 376 Phospholipases, 231, 376, 389 Phospholipids, 231, 344, 361, 376 Phosphorus, 326, 376 Phosphorylate, 223, 234, 376 Phosphorylated, 20, 38, 62, 376 Phosphorylating, 20, 376
Phosphorylation, 31, 38, 64, 89, 91, 94, 96, 233, 238, 376 Photodynamic therapy, 208, 255, 376 Photophobia, 358, 376 Photosensitizer, 208, 376 Photosensitizing Agents, 376, 395 Phototherapy, 137, 376 Physical Examination, 188, 377 Physiologic, 31, 213, 242, 317, 324, 358, 377, 383 Physiology, 15, 213, 222, 257, 315, 323, 346, 377 Pigment, 337, 364, 371, 377 Pigmentation, 259, 264, 377 Pituitary Gland, 334, 345, 377 Plants, 317, 330, 348, 358, 360, 366, 370, 377, 378, 386, 391, 395, 396, 397 Plaque, 67, 172, 213, 214, 256, 329, 377 Plasma, 9, 45, 53, 89, 101, 133, 185, 231, 320, 328, 329, 348, 350, 365, 367, 377, 383, 388, 400 Plasma cells, 320, 377 Plasmid, 28, 82, 85, 209, 377, 399 Plasticity, 21, 377 Plastids, 372, 377 Platelet Activation, 377, 389 Platelet Aggregation, 318, 345, 377 Pleura, 377 Pleural, 102, 377 Pleural cavity, 377 Pleural Effusion, 102, 377 Point Mutation, 50, 378 Polioviruses, 232, 378 Pollen, 378, 382 Polyethylene, 328, 378 Polymerase Chain Reaction, 6, 26, 51, 108, 131, 179, 378 Polymorphism, 68, 108, 378 Polyposis, 331, 378 Polysaccharide, 53, 163, 320, 328, 378, 381 Polytetrafluoroethylene, 142, 378 Posterior, 40, 318, 329, 339, 348, 358, 372, 373, 378, 387 Postoperative, 267, 378 Postsynaptic, 369, 378, 389, 393 Post-translational, 238, 378 Potentiates, 28, 126, 357, 378 Potentiation, 361, 379, 389 Poxviridae, 232, 374, 379 Practice Guidelines, 291, 298, 379 Precipitating Factors, 297, 350, 379 Preclinical, 16, 34, 35, 59, 379
416 Herpes Simplex
Precursor, 9, 238, 340, 342, 370, 376, 379, 390, 397 Predisposition, 231, 379 Presynaptic, 172, 368, 369, 379, 393 Presynaptic Terminals, 368, 379 Prevalence, 17, 32, 37, 52, 125, 136, 139, 141, 172, 235, 251, 259, 262, 371, 379 Primary tumor, 210, 379 Prion, 328, 379 Probe, 57, 90, 91, 115, 160, 371, 379 Prodrug, 20, 55, 154, 233, 379 Progeny, 24, 31, 55, 76, 196, 379 Progesterone, 90, 379, 391 Progression, 21, 28, 42, 57, 78, 89, 101, 180, 183, 230, 259, 272, 319, 379, 380 Progressive, 69, 257, 327, 336, 339, 343, 349, 368, 377, 379, 397 Projection, 336, 357, 370, 372, 380 Proliferating Cell Nuclear Antigen, 204, 380 Proline, 149, 331, 380 Promyelocytic leukemia, 140, 380 Prophase, 366, 380, 393 Prophylaxis, 143, 155, 213, 214, 218, 252, 272, 321, 337, 380, 386, 398 Propolis, 148, 157, 158, 230, 380 Proportional, 52, 160, 342, 380 Prospective study, 101, 122, 380 Prostate, 34, 111, 163, 380 Protease, 42, 56, 72, 84, 94, 331, 380 Protein C, 31, 318, 321, 323, 361, 380, 398, 400 Protein Conformation, 318, 380 Protein Kinases, 371, 380 Protein S, 164, 196, 205, 223, 225, 231, 255, 321, 324, 333, 346, 380, 385, 394 Protein Transport, 25, 380 Proteoglycans, 53, 60, 323, 344, 381 Proteolytic, 25, 90, 332, 381 Protocol, 10, 34, 195, 381 Protons, 317, 353, 358, 381, 382 Proto-Oncogenes, 371, 381 Protozoa, 324, 359, 365, 381, 390, 395 Protozoal, 260, 381 Protozoan Infections, 328, 381 Proximal, 214, 339, 379, 381 Pruritic, 337, 340, 360, 381 Pseudorabies, 27, 124, 381 Psoriasis, 137, 245, 376, 381 Psychiatric, 138, 364, 381 Psychiatry, 103, 105, 119, 137, 138, 149, 344, 381
Psychic, 381, 387 Psychogenic, 381, 398 Psychosexual, 381, 388 Puberty, 194, 217, 256, 381 Public Health, 47, 256, 290, 291, 381 Public Policy, 289, 382 Publishing, 3, 5, 60, 215, 250, 251, 260, 262, 263, 382 Pulmonary, 12, 133, 324, 333, 334, 382, 393, 399 Pulmonary hypertension, 334, 382 Pulse, 104, 195, 366, 382 Pupil, 334, 338, 358, 382 Purpura, 250, 259, 382 Purulent, 382, 398 Pustular, 355, 382 Putrescine, 372, 382, 390 Pyogenic, 343, 373, 382, 388 Pyridoxal, 372, 382 Q Quercetin, 156, 243, 382 Quiescent, 22, 23, 62, 150, 234, 382, 400 R Race, 365, 382 Radiation therapy, 253, 266, 316, 343, 357, 359, 382, 401 Radioactive, 325, 353, 355, 357, 358, 359, 361, 366, 370, 371, 382, 383, 386, 401 Radioimmunotherapy, 382, 383 Radioisotope, 371, 383 Radiolabeled, 173, 359, 382, 383, 401 Radiotherapy, 111, 121, 210, 258, 325, 359, 382, 383, 401 Randomized, 5, 49, 62, 70, 100, 107, 143, 154, 178, 184, 340, 383 Rape, 253, 383 Reagent, 202, 219, 362, 383 Receptors, Cytokine, 179, 383 Recombinant Proteins, 209, 222, 240, 383 Recombination, 11, 173, 217, 383 Reconstitution, 77, 113, 383 Rectal, 31, 46, 166, 383 Rectum, 321, 325, 331, 338, 346, 356, 359, 380, 383, 393 Recur, 196, 276, 383 Recurrence, 4, 12, 38, 47, 55, 70, 127, 143, 189, 194, 208, 217, 243, 244, 297, 298, 383 Reductase, 34, 64, 72, 73, 97, 126, 141, 172, 192, 209, 215, 242, 383, 394 Refer, 1, 325, 331, 345, 351, 357, 361, 366, 367, 369, 383 Reflux, 266, 346, 383
Index 417
Refraction, 383, 390 Refractory, 181, 383 Regeneration, 383 Regimen, 37, 178, 179, 258, 340, 383 Regression Analysis, 6, 384 Regurgitation, 346, 384 Rehabilitative, 261, 384 Relative risk, 52, 384 Relaxant, 345, 384 Reliability, 84, 129, 384 Remission, 383, 384 Replicon, 19, 384 Repressor, 196, 239, 240, 371, 384 Resected, 26, 384 Respiration, 365, 366, 384 Restoration, 383, 384, 401 Resuscitation, 341, 384 Retina, 39, 104, 329, 330, 333, 369, 372, 384, 385, 386, 398, 401 Retinal, 104, 116, 125, 141, 371, 372, 385, 400 Retinal Ganglion Cells, 372, 385 Retinitis, 40, 173, 208, 252, 385 Retinoblastoma, 131, 385 Retinol, 385 Retinopathy, 104, 385 Retrograde, 196, 275, 385 Retrospective, 109, 128, 385 Retrospective study, 128, 385 Retroviral vector, 12, 149, 385 Retrovirus, 20, 29, 34, 59, 101, 385 Rhabdomyosarcoma, 163, 385 Rheumatic Diseases, 245, 385 Rhinitis, 385, 388 Rhinovirus, 232, 385 Ribose, 316, 385 Ribosome, 89, 98, 385, 396 Risk factor, 6, 29, 47, 52, 138, 139, 200, 342, 361, 380, 384, 385 Risk patient, 244, 386 Rod, 323, 330, 343, 386 Rotavirus, 217, 386 Rubella, 232, 250, 256, 257, 259, 260, 264, 386 Rubella Virus, 232, 386 Rural Health, 49, 386 Rural Population, 386 Rutin, 382, 386 S Safe Sex, 179, 253, 386 Saliva, 5, 49, 251, 386
Salivary, 5, 250, 259, 262, 264, 265, 336, 338, 344, 386, 401 Salivary glands, 336, 338, 344, 386 Saponins, 386, 391 Sarcoidosis, 262, 386 Sarcoma, 9, 27, 41, 65, 218, 250, 251, 252, 259, 260, 263, 267, 386 Scans, 25, 386 Scarlet Fever, 261, 387 Schizogony, 387, 391 Schizoid, 387, 401 Schizophrenia, 103, 387, 401 Schizotypal Personality Disorder, 387, 401 Sclera, 329, 333, 387, 398 Scleroderma, 260, 387 Screening, 15, 91, 113, 114, 132, 196, 228, 330, 387 Sebaceous, 387, 401 Second Messenger Systems, 369, 387 Secondary tumor, 365, 387 Secretion, 12, 231, 334, 352, 357, 365, 366, 387, 398 Secretory, 231, 369, 387, 393 Secretory Vesicles, 231, 387 Segregation, 22, 383, 387 Seizures, 26, 347, 387 Self Mutilation, 256, 387 Semen, 31, 46, 110, 117, 340, 380, 387 Senile, 258, 388 Sensibility, 318, 353, 388 Sensitization, 59, 388 Sepsis, 123, 388 Septicaemia, 388 Sequence Analysis, 50, 388 Sequencing, 56, 378, 388 Seroconversion, 237, 388 Serologic, 29, 32, 67, 84, 112, 354, 388 Serologic Tests, 29, 388 Serology, 14, 74, 113, 138, 388 Serotypes, 60, 135, 217, 218, 237, 335, 388 Sex Behavior, 312, 388 Sex Characteristics, 316, 319, 381, 388, 394 Sex Counseling, 189, 388 Sexual Abstinence, 297, 388 Sexual Partners, 243, 252, 388 Sharpness, 388, 400 Shedding, 29, 35, 56, 68, 108, 120, 148, 276, 388, 400 Shock, 388, 396 Side effect, 183, 186, 188, 243, 244, 281, 316, 324, 389, 395 Signal Transduction, 231, 389
418 Herpes Simplex
Signs and Symptoms, 188, 263, 298, 384, 389 Sindbis Virus, 70, 317, 389 Skeletal, 227, 260, 319, 330, 389 Skeleton, 359, 389 Skull, 335, 389, 394 Small cell lung cancer, 389 Small intestine, 324, 330, 340, 352, 357, 389 Smallpox, 257, 389, 398 Smooth muscle, 214, 318, 345, 352, 389, 392 Sneezing, 311, 388, 389 Social Support, 163, 389, 392 Sodium, 31, 71, 94, 242, 365, 389 Soft tissue, 250, 263, 325, 389, 390 Solid tumor, 194, 319, 390 Solvent, 216, 348, 372, 376, 390 Soma, 390 Somatic, 36, 316, 347, 352, 364, 365, 375, 390 Specialist, 153, 300, 338, 390 Specificity, 37, 50, 53, 76, 202, 226, 240, 316, 321, 390 Specimen Handling, 14, 390 Spectrum, 16, 34, 107, 196, 197, 235, 260, 390, 399 Sperm, 149, 282, 319, 330, 378, 390 Spermatozoa, 388, 390 Spermidine, 372, 390 Spinal cord, 177, 322, 325, 328, 329, 340, 346, 358, 363, 364, 368, 369, 373, 375, 390 Spinal Nerves, 375, 390 Spirochete, 362, 390, 393 Spleen, 46, 336, 362, 386, 390 Splenomegaly, 356, 390 Sporadic, 11, 385, 390 Spores, 356, 390 Sporozoite, 15, 391 Squamous, 252, 257, 263, 265, 342, 370, 391 Squamous cell carcinoma, 252, 263, 265, 342, 370, 391 Squamous cells, 391 Staging, 386, 391 Staphylococcus, 346, 355, 391 Staphylococcus aureus, 346, 355, 391 Statistically significant, 56, 391 Steel, 330, 391, 397 Stem Cells, 350, 391 Sterile, 7, 216, 391 Sterility, 110, 356, 391 Steroid, 21, 323, 386, 391 Stimulant, 352, 391
Stimulus, 25, 33, 42, 231, 339, 340, 358, 359, 391, 394 Stomach, 246, 315, 326, 338, 343, 346, 350, 352, 361, 367, 371, 375, 376, 383, 389, 390, 391 Stomatitis, 90, 194, 257, 259, 268, 279, 392 Strand, 148, 378, 392 Streptococcal, 250, 269, 392 Streptococci, 355, 387, 392 Streptococcus, 392 Stress management, 163, 392 Striatum, 28, 392 Stridor, 335, 392 Stroke, 190, 288, 326, 392 Stromal, 8, 11, 15, 33, 47, 102, 180, 184, 244, 392 Subacute, 356, 362, 392 Subarachnoid, 350, 376, 392 Subclinical, 199, 219, 356, 387, 392 Subcutaneous, 340, 346, 374, 392 Subiculum, 352, 392 Subspecies, 390, 392, 398 Substance P, 364, 383, 387, 392 Substrate, 26, 96, 234, 342, 368, 392 Substrate Specificity, 234, 392 Sunburn, 211, 393 Suppositories, 365, 393 Suppression, 52, 87, 131, 139, 181, 185, 208, 252, 276, 334, 393 Suppressive, 153, 178, 393 Surfactant, 216, 328, 370, 393, 401 Survival Rate, 179, 393 Sympathomimetic, 342, 370, 393 Symphysis, 380, 393 Symptomatic, 185, 219, 243, 393 Synapses, 361, 369, 393 Synapsis, 393 Synaptic, 21, 361, 389, 393 Synergistic, 59, 393 Syphilis, 180, 250, 251, 252, 253, 257, 260, 264, 269, 393 Systemic disease, 4, 23, 261, 265, 393 T Tacrolimus, 102, 393 Taste Disorders, 253, 258, 393 Tea Tree Oil, 158, 169, 394 Temporal, 26, 94, 344, 350, 352, 394, 397 Temporal Lobe, 26, 394 Teratogenic, 264, 317, 394 Testis, 236, 394 Testosterone, 383, 394 Tetracycline, 20, 140, 240, 394
Index 419
Therapeutics, 12, 33, 49, 154, 283, 394 Thermal, 339, 369, 378, 394 Thioredoxin, 41, 394 Third Ventricle, 353, 394 Threshold, 35, 353, 394 Thrombin, 377, 380, 394 Thrombomodulin, 380, 394 Thrombosis, 380, 392, 394 Thrombus, 334, 356, 367, 377, 394 Thymidine Kinase, 6, 12, 19, 34, 51, 55, 61, 68, 80, 91, 92, 99, 105, 106, 108, 110, 112, 113, 118, 119, 121, 125, 126, 127, 128, 132, 133, 148, 149, 150, 151, 154, 157, 160, 162, 163, 164, 173, 174, 215, 224, 233, 234, 242, 244, 394 Thymus, 330, 354, 362, 394 Thyroid, 118, 395, 397 Ticks, 362, 395 Time Management, 392, 395 Tin, 208, 311, 395 Tin ethyl etiopurpurin, 208, 395 Tissue Culture, 23, 33, 38, 91, 164, 172, 395 Tolerance, 181, 185, 186, 187, 206, 207, 315, 348, 395 Tome, 158, 395 Tomography, 34, 157, 160, 163, 173, 332, 395 Tonsillitis, 387, 395 Toothache, 260, 395 Topotecan, 154, 395 Toxic, iv, 15, 154, 207, 224, 244, 257, 266, 317, 336, 340, 354, 369, 382, 395 Toxicity, 18, 19, 48, 55, 79, 174, 188, 208, 227, 240, 339, 395 Toxicology, 290, 395 Toxins, 207, 320, 341, 348, 356, 364, 366, 382, 395 Toxoplasma, 193, 217, 252, 395 Toxoplasmosis, 256, 257, 260, 264, 395 Trace element, 330, 395 Trachea, 325, 376, 392, 395 Traction, 330, 396 Transcriptase, 18, 51, 69, 336, 370, 385, 396 Transcription Factors, 34, 38, 50, 66, 125, 240, 371, 396, 400 Transdermal, 204, 396 Transduction, 22, 34, 104, 149, 154, 227, 231, 389, 396 Transfection, 199, 209, 324, 396 Transfer Factor, 354, 396 Transferases, 348, 396 Transfusion, 351, 396
Transgenes, 12, 14, 19, 20, 21, 396 Translation, 21, 52, 96, 217, 396 Translational, 39, 59, 99, 238, 396 Translocating, 114, 396 Translocation, 50, 92, 145, 381, 396 Transmitter, 322, 358, 363, 369, 370, 393, 396 Transplantation, 19, 105, 130, 135, 143, 155, 214, 247, 354, 363, 396 Trauma, 26, 33, 115, 180, 204, 235, 264, 297, 343, 368, 396, 401 Trees, 318, 343, 396 Trichomoniasis, 251, 396 Tricuspid Atresia, 334, 396 Trigeminal, 15, 33, 40, 52, 55, 63, 69, 80, 82, 90, 92, 94, 97, 98, 103, 137, 363, 397 Trigeminal Ganglion, 33, 52, 80, 82, 397 Trigeminal Nerve, 397 Trophic, 21, 397 Tropism, 22, 122, 397 Tuberculosis, 262, 267, 269, 333, 362, 397 Tuberous Sclerosis, 20, 397 Tumor Necrosis Factor, 98, 100, 130, 229, 230, 236, 397 Tumor suppressor gene, 20, 397 Tumour, 346, 371, 397 Tungsten, 327, 397 Tyrosine, 28, 131, 220, 231, 327, 397 U Ubiquitin, 94, 138, 140, 173, 397 Ulcer, 102, 256, 340, 397 Ulceration, 5, 18, 134, 199, 206, 216, 245, 260, 263, 265, 267, 372, 397 Ulcerative colitis, 261, 356, 397 Unconscious, 319, 336, 354, 397 Uracil, 34, 59, 187, 210, 398 Urban Population, 52, 398 Urea, 372, 398 Ureters, 398 Urethra, 375, 380, 398 Urethritis, 132, 398 Urinary, 267, 268, 347, 398 Urinary Retention, 268, 398 Urinary tract, 267, 398 Urinary tract infection, 267, 398 Urinate, 398 Urine, 49, 324, 398 Urogenital, 347, 348, 398 Uterus, 328, 340, 353, 373, 379, 398 Uvea, 398 Uveitis, 35, 39, 144, 268, 398
420 Herpes Simplex
V Vaccination, 8, 16, 56, 84, 152, 200, 225, 237, 245, 272, 398 Vaccinia, 30, 194, 257, 259, 398, 399 Vaccinia Virus, 194, 259, 398, 399 Vacuoles, 372, 398 Vagina, 46, 86, 326, 328, 331, 337, 398 Vaginal, 18, 31, 40, 46, 48, 49, 58, 82, 87, 99, 138, 149, 188, 212, 282, 311, 370, 398, 399 Vaginitis, 251, 326, 398 Vaginosis, 103, 251, 399 Variola, 259, 398, 399 Vascular, 20, 26, 214, 245, 246, 257, 329, 350, 356, 394, 398, 399 Vasoconstriction, 342, 399 Vasodilation, 246, 399 Vasodilator, 352, 399 Vasomotor, 245, 399 Vein, 319, 358, 370, 374, 399 Venereal, 253, 393, 399 Venous, 380, 396, 399 Ventricle, 322, 334, 352, 382, 394, 396, 399 Ventricular, 333, 396, 399 Venules, 325, 399 Verruca, 257, 265, 399 Vertebrae, 390, 399 Vesicular, 90, 137, 194, 216, 257, 337, 349, 351, 381, 389, 399 Veterinary Medicine, 289, 399 Vibrio, 37, 207, 329, 399 Vibrio cholerae, 37, 207, 329, 399 Vidarabine, 183, 283, 399 Villous, 327, 399 Vinca Alkaloids, 399, 400 Vincristine, 163, 399 Viral Envelope Proteins, 231, 236, 400 Viral Hepatitis, 265, 400 Viral Load, 137, 400 Viral vector, 14, 19, 21, 30, 34, 59, 108, 118, 119, 213, 225, 244, 400 Virulence, 11, 47, 61, 63, 65, 98, 105, 153, 205, 268, 322, 395, 400 Virulent, 46, 91, 400 Virus Diseases, 321, 400 Virus Latency, 51, 73, 76, 220, 221, 234, 400
Virus Replication, 10, 33, 35, 76, 83, 87, 92, 94, 151, 161, 202, 234, 400 Virus Shedding, 6, 35, 48, 100, 181, 197, 400 Viscera, 367, 390, 400 Visceral, 245, 246, 323, 347, 400 Visual Acuity, 33, 400 Vitiligo, 245, 400 Vitreous Body, 329, 384, 401 Vitro, 9, 15, 17, 18, 19, 21, 23, 25, 30, 31, 36, 41, 43, 45, 48, 54, 59, 64, 66, 70, 77, 78, 79, 82, 87, 88, 91, 92, 96, 100, 106, 113, 124, 125, 139, 151, 152, 153, 161, 164, 185, 187, 192, 199, 201, 205, 208, 224, 227, 234, 350, 355, 378, 388, 393, 395, 401 Vivo, 9, 15, 17, 19, 20, 22, 23, 31, 36, 41, 42, 48, 54, 56, 59, 63, 64, 66, 70, 77, 78, 82, 84, 86, 87, 89, 90, 92, 97, 139, 150, 151, 153, 161, 163, 164, 172, 192, 199, 210, 221, 224, 227, 237, 350, 355, 393, 401 Voltage-gated, 315, 401 Vulgaris, 169, 174, 218, 257, 260, 264, 265, 315, 401 W Wart, 359, 401 Weight-Bearing, 373, 401 Wetting Agents, 370, 401 White blood cell, 179, 315, 320, 330, 355, 356, 360, 362, 363, 366, 367, 377, 401 Windpipe, 376, 395, 401 Withdrawal, 12, 39, 401 Wound Healing, 44, 363, 401 Wound Infection, 121, 401 X Xenograft, 246, 319, 401 Xerostomia, 253, 258, 263, 264, 267, 401 X-ray, 43, 54, 327, 332, 345, 359, 370, 382, 383, 386, 401 X-ray therapy, 359, 401 Y Yeasts, 326, 345, 376, 401 Yellow Fever, 265, 401 Z Zygote, 332, 391, 402 Zymogen, 380, 402
Index 421
422 Herpes Simplex
Index 423
424 Herpes Simplex
