Helicobacter Pylori - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HELICOBACTER PYLORI A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J...

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HELICOBACTER PYLORI A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AM ES N. P ARK ER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Helicobacter Pylori: 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: 0-597-84447-X 1. Helicobacter Pylori-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Helicobacter pylori. 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 HELICOBACTER PYLORI ............................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Helicobacter Pylori...................................................................... 62 E-Journals: PubMed Central ..................................................................................................... 123 The National Library of Medicine: PubMed .............................................................................. 167 CHAPTER 2. NUTRITION AND HELICOBACTER PYLORI ................................................................ 215 Overview.................................................................................................................................... 215 Finding Nutrition Studies on Helicobacter Pylori .................................................................... 215 Federal Resources on Nutrition ................................................................................................. 223 Additional Web Resources ......................................................................................................... 224 CHAPTER 3. DISSERTATIONS ON HELICOBACTER PYLORI ............................................................ 225 Overview.................................................................................................................................... 225 Dissertations on Helicobacter Pylori ......................................................................................... 225 Keeping Current ........................................................................................................................ 226 CHAPTER 4. PATENTS ON HELICOBACTER PYLORI....................................................................... 227 Overview.................................................................................................................................... 227 Patents on Helicobacter Pylori................................................................................................... 227 Patent Applications on Helicobacter Pylori............................................................................... 247 Keeping Current ........................................................................................................................ 280 CHAPTER 5. BOOKS ON HELICOBACTER PYLORI .......................................................................... 281 Overview.................................................................................................................................... 281 Book Summaries: Federal Agencies............................................................................................ 281 Book Summaries: Online Booksellers......................................................................................... 282 Chapters on Helicobacter Pylori ................................................................................................ 285 CHAPTER 6. MULTIMEDIA ON HELICOBACTER PYLORI ............................................................... 289 Overview.................................................................................................................................... 289 Video Recordings ....................................................................................................................... 289 CHAPTER 7. PERIODICALS AND NEWS ON HELICOBACTER PYLORI ............................................ 291 Overview.................................................................................................................................... 291 News Services and Press Releases.............................................................................................. 291 Newsletter Articles .................................................................................................................... 296 Academic Periodicals covering Helicobacter Pylori ................................................................... 297 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 299 Overview.................................................................................................................................... 299 U.S. Pharmacopeia..................................................................................................................... 299 Commercial Databases ............................................................................................................... 300 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 305 Overview.................................................................................................................................... 305 NIH Guidelines.......................................................................................................................... 305 NIH Databases........................................................................................................................... 307 Other Commercial Databases..................................................................................................... 309 The Genome Project and Helicobacter Pylori............................................................................. 309 APPENDIX B. PATIENT RESOURCES ............................................................................................... 313 Overview.................................................................................................................................... 313 Patient Guideline Sources.......................................................................................................... 313 Finding Associations.................................................................................................................. 322 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 325 Overview.................................................................................................................................... 325 Preparation................................................................................................................................. 325

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Finding a Local Medical Library................................................................................................ 325 Medical Libraries in the U.S. and Canada ................................................................................. 325 ONLINE GLOSSARIES................................................................................................................ 331 Online Dictionary Directories ................................................................................................... 331 HELICOBACTER PYLORI DICTIONARY............................................................................... 333 INDEX .............................................................................................................................................. 417

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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 Helicobacter pylori 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 Helicobacter pylori, 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 Helicobacter pylori, 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 Helicobacter pylori. 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 Helicobacter pylori, 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 Helicobacter pylori. 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 HELICOBACTER PYLORI Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Helicobacter pylori.

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

Review Article: Helicobacter Pylori and Gastro-Oesophageal Reflux Disease. Clinical Implications and Management Source: Alimentary Pharmacology and Therapeutics. 13(2): 117-127. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: A significant proportion of patients with gastroesophageal reflux disease (GERD) have Helicobacter pylori infection, but it is unclear whether H. pylori should be treated in this clinical setting. This review article critically assesses the relationship between H. pylori and GERD and its potential implications for the management of

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GERD. Data for the review were gathered from the biomedical database MEDLINE, a detailed review of medical journals, and a review of abstracts submitted to relevant international meetings, up to April 1998. On average, 40 percent of GERD patients carry H. pylori infection, with a reported infection prevalence ranging from 16 to 88 percent. To date, there has been no reported controlled trial of effective H. pylori therapy in GERD. GERD has been reported to develop de novo following the cure of H. pylorirelated peptic ulcer disease. In the presence of H. pylori, proton pump inhibitor therapy appears to accelerate the development of atrophic corpus gastritis, a potentially precancerous condition. Conversely, proton pump inhibitor therapy seems to become less effective after cure of H. pylori. The mechanisms underlying these important contrasting phenomena are poorly understood. The author concludes that the relationship between H. pylori and GERD is complex, and it is difficult to give definitive guidelines on the management of H. pylori infection in GERD. Controlled trials of H. pylori therapy in CERD are urgently needed, as well as further long term data on both the natural history of gastric histopathological changes in the H. pylori positive GERD patient treated with proton pump inhibitors, and the impact of H. pylori status on the clinical efficacy of antisecretory therapy. Pending these data, it is perhaps advisable to advocate cure of H. pylori in young patients with proton pump inhibitor dependent GERD who, in the absence of antireflux surgery, are faced with the likelihood of long term medical therapy. 2 tables. 108 references. (AA-M). •

Eradication of Helicobacter Pylori May Reduce Disease Severity in Rheumatoid Arthritis Source: Alimentary Pharmacology and Therapeutics. 16(7):1291-1299. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: A triggering infectious agent has long been postulated in rheumatoid arthritis. Data on the possible role of Helicobacter pylori are lacking. This article reports on a study undertaken to assess the effect of H. pylori eradication in patients with rheumatoid arthritis (RA). The study included 58 adults patients with established RA and dyspeptic symptoms; 28 were H. pylori positive and 30 were H. pylori negative on the basis of invasive tests. All infected patients were treated successfully. The authors found that H. pylori-eradicated RA patients showed progressive improvement over time of all clinical indices, compared with baseline, whereas H. pylori-negative RA patients remained substantially unchanged. After 2 years, H. pylori-eradicated RA patients differed significantly from patients without H. pylori infection in terms of improvement of all clinical parameters. The authors conclude that their data suggest that H. pylori infection is implicated in the pathogenesis (development) of RA, in that its eradication may induce a significant improvement of disease activity over 24 months. H. pylori eradication seems to be advantageous in infected RA patients, but controlled studies are needed. 3 figures. 3 tables. 26 references.

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Helicobacter Pylori Infection, Gastritis and Gastric Cancer: A Short-Term Eradication Therapy for Helicobacter Pylori Acute Gastritis Source: Journal of Gastroenterology and Hepatology. 15(12): 1377-1381. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com.

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Summary: Acute gastritis (stomach inflammation), caused by an initial infection of Helicobacter pylori, may resolve spontaneously, but the infection sometimes becomes chronic. The authors of this article examined the efficacy of a short term H. pylori eradication therapy on acute gastritis. Among the 15 patients with hemorrhage acute gastritis who were randomly allocated to group A (eradication therapy) or group B (lansoprazole), 10 of the patients started to receive treatment within 1 day after the disease onset. The other five patients began the eradication therapy 4 to 6 days after disease onset (group C). Eradication therapy consisted of a daily oral administration of each of 30 milligrams lansoprazole (LPZ) once a day; 400 milligrams clarithromycin, twice a day; 1000 milligrams amoxicillin, twice a day; and 300 milligrams rebamipide, three times a day, for one week. If the endoscopy was normal, medication was stopped for the following 4 weeks before gastric endoscopy was performed again in order to assess H. pylori eradication. All group A patients were cured after the 1 week treatment and, therefore, they became H. pylori negative. Group B and C patients had erosions or ulcers after the 1 week treatment and so received an additional 3 week administration of LPZ. Four weeks later, their gastritis was cured and except for one group B patient, they became H. pylori negative. The authors conclude that in patients with acute gastritis, caused by an initial H. pylori infection, eradication therapy was efficacious in achieving early healing. This therapy should therefore be started as soon as possible after disease onset. 1 table. 25 references. •

Cure of Helicobacter Pylori Infection in Elderly Patients: Comparison of Low Versus High Doses of Clarithromycin in Combination with Amoxicillin and Pantoprazole Source: Alimentary Pharmacology and Therapeutics. 15(7): 1031-1036. July 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Advancing age may influence the pharmacokinetics of the antibiotic clarithromycin. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor (PPI) and amoxicillin in elderly patients. This article reports on a study undertaken to compare the efficacy and tolerability of clarithromycin 250 milligrams versus clarithromycin 500 milligrams twice daily (b.d.) in combination with pantoprazole (a PPI) and amoxicillin in elderly patients. Subjects were 154 elderly patients with Helicobacter pylori associated ulcer disease or chronic gastritis (inflamed stomach). They were randomized to receive pantoprazole 40 milligrams daily plus amoxicillin 1 gram and either clarithromycin 250 milligrams b.d. (PAC 250) or clarithromycin 500 milligrams b.d. (PAC 500). Two months after therapy, endoscopy and gastric (stomach) biopsies were repeated. The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively 83 percent and 79 percent (using the intention to treat, or ITT, analysis) and 94 percent and 88 percent respectively (using the per protocol, or PP, analysis). Significant decreases in chronic gastritis activity both in the body and the antrum of the stomach were found in H. pylori cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5 percent) and seven in PAC 500 (9 percent) reported adverse events. Of these, one patient in PAC 250 (25 percent) and three in PAC 500 (43 percent) discontinued the study because of these drug related side effects. The authors conclude that in elderly patients, 1 week triple therapy with a PPI, amoxicillin, and clarithromycin is a highly effective and well tolerated anti H. pylori treatment. With this combination, clarithryomycin at the lower dose of 250 milligrams b.d. achieved excellent cure rates and minimized adverse events and costs. 2 tables. 22 references.

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H. Pylori Eradication for Individuals on Chronic NSAID Therapy: Should We Kill the Bug If You Need the Drug? Source: Practical Gastroenterology. 25(5): 12, 16, 19, 23-24. May 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Although it is widely agreed that Helicobacter pylori (a bacterium) causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID associated complications. This article considers the role of H. pylori eradication for individuals on chronic NSAID therapy. H. pylori gastritis can increase protective prostaglandin levels in the upper GI tract mucosa, but there is little evidence that eradication of infection leads to an increased risk for clinically significant events in those taking NSAIDs. Since both H. pylori and NSAIDs increase ulcer risk, elimination of either risk factor does not provide protection against the other. Given the prevalence of NSAID associated toxicity, preventive strategies to reduce NSAID side effects remain important. In addition, a compelling argument can be made for H. pylori testing of chronic NSAID users at increased risk for ulcer disease, from the cost effectiveness standpoint. Testing for H. pylori does not appear to be indicated for all patients starting on NSAID therapy. Patients with a pre existing history of peptic ulcer disease should be tested for H. pylori and treated with antibiotics if the test is positive, in order to reduce recurrence of H. pylori associated ulcers. 1 figure. 14 references.

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Helicobacter Pylori Screening for Individuals Requiring Chronic NSAID Therapy: A Decision Analysis Source: Alimentary Pharmacology and Therapeutics. 15(1): 63-71. January 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Although it is without question that Helicobacter pylori causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID (nonsteroidal antiinflammatory drugs) related complications and whether H. pylori eradication reduces the rate of adverse events. This article reports on a symptom driven decision analytic model that was developed to compare the clinical and economic impact of H. pylori screening compared to a strategy of no H. pylori testing for individuals requiring chronic NSAID therapy. In the principal analysis, it was assumed that untreated H. pylori infection increased the ulcer risk by 50 percent and that successful eradication reduced the risk of adverse events to that of uninfected patients. Patients' ulcer risk and the protective effect of H. pylori eradication were evaluated using sensitivity analysis. When compared to no H. pylori testing, H. pylori screening led to fewer symptomatic ulcers and ulcer complications and a higher cost per patient. The incremental cost attributable to the H. pylori screening strategy to prevent a symptomatic and complicated ulcer was $16,805 and $31,842 respectively. The clinical and cost effectiveness advantage of H. pylori screening improved as patients' ulcer risk increased or the protective effect of H. pylori eradication was enhanced. The authors conclude that based upon the available evidence, H. pylori screening has the potential to reduce NSAID related adverse events for average risk patients at an incremental cost. Until controlled investigations definitively quantify the effect of H. pylori eradication on clinically significant NSAID related adverse events, a compelling argument can be made for H. pylori testing for chronic NSAID users at increased risk of ulcer disease. 3 figures. 2 tables. 32 references.

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Ranitidine Bismuth Citrate, Tetracycline, Clarithromycin Twice-A-Day Triple Therapy for Clarithromycin Susceptible Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 13(2): 169-172. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. This article reports on a study undertaken to investigate the role of the new soluble form of bismuth (ranitidine bismuth citrate) in twice a day therapy for Helicobacter pylori infection. Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). Sixty three patients completed the therapy (59 men and 4 women; average age 56.7 years, range 31 to 75 years). All patients had clarithromycin susceptible strains prior to therapy. H. pylori infection was cured in 94 percent. There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side effects. Three of the isolates from treatment failures were available post failure; two were clarithromycin resistant and one was susceptible. Side effects, primarily diarrhea, were severe in two patients (3 percent) and moderate in three. The authors conclude that this therapeutic regimen was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin susceptible H. pylori. 33 references. (AA-M).

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Eradication of Helicobacter Pylori Prevents Ulcer Development in Patients with Ulcer-Like Functional Dyspepsia Source: Alimentary Pharmacology and Therapeutics. 15(2): 195-201. February 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the bacterial infection in the patients with functional dyspepsia (FD, includes heartburn as a primary symptom) remains controversial. This article reports on a study undertaken to determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of FD patients. In the double blind, placebo controlled trial, 161 patients infected with H. pylori who had FD were randomly assigned to 7 days of treatment with a lansoprazole based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms. H. pylori was eradicated in 63 out of 81 patients (78 percent) in the treatment group and none of the 80 patients (0 percent) in the placebo group. During the followup period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5 percent versus 7.5 percent). The reduction in ulcer rates was statistically significant in the 'ulcer like' subgroup but not in the 'dysmotility like' and 'unclassifiable' subgroups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58 percent versus 55 percent, respectively). Additionally, no significant differences

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existed in the symptom responses between the treatment and control arms in each of the dyspepsia subgroups. The authors conclude that eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with 'ulcer like' FD. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients. 2 figures. 2 tables. 26 references. •

Trend Toward a Reduced Prevalence of Helicobacter Pylori Infection, Chronic Gastritis, and Gastric Cancer in Japan Source: Gastroenterology Clinics of North America. 29(3): 623-631. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Although there has been a remarkable decline in the prevalence and mortality (death) rates of gastric (stomach) cancer in developed countries, gastric cancer is one of the common malignancies in the world and is still the main cause of death in Japan. This article investigates the trends in Helicobacter pylori infection and gastritis in Japan over the past few decades. The author notes that it is important to investigate the relationship between H. pylori infection and gastric cancer and gastritis to understand better the mechanisms for carcinogenesis (the development of cancer) in the stomach. The author speculates that declines in H. pylori infection and gastritis over the past few decades may lead to a decline in gastric cancer in Japan, supplemented by excellent procedures for the early detection of gastric cancer. H. pylori infection rarely is acquired in adult life, so once it is eradicated, reinfection is not expected in adult patients. The author concludes that adequate treatment of H. pylori provides long term protection against gastric cancer.

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Helicobacter Pylori Infection and Anorexia of Aging (commentary) Source: Archives of Internal Medicine. 157(3): 269-272. February 10, 1997. Summary: Anorexia and malnutrition are frequently encountered problems in the geriatric patient population. Anorexia of aging, i.e., anorexia caused by the aging process itself, has been proposed as the cause of clinically unexplained anorexia in patients of advanced age. In this article, the author reports three cases in which anorexia and geriatric failure-to-thrive (GFTT) syndrome were associated with Helicobacter pylori, then reversed after treatment with antibiotics and a hydrogen-ion proton inhibitor. The clinical presentation of the infection was characterized by the lack of symptoms typically associated with gastric diseases, such as nausea, vomiting, dyspepsia, and abdominal pain. Instead, patients exhibited signs of aversion to food, decline in mental functions, and the inability to perform activities of daily living. The possible causative relationship between H. pylori infection, anorexia of aging, and GFTT syndrome is suggested by the presented cases. The author calls for a major clinical study to explore this relationship. 12 references.

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Helicobacter Pylori Infection as a Risk Factor for Gastrointestinal Symptoms in Patients Using Aspirin to Prevent Ishaemic Heart Disease Source: Alimentary Pharmacology and Therapeutics. 15(7): 1055-1059. July 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com.

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Summary: Aspirin use in the secondary prevention of ischemic heart disease may provoke gastrointestinal (GI) discomfort. This article reports on a study undertaken to register GI symptoms and complications in patients with cardiovascular disease using aspirin and to relate these symptoms to infection with H. pylori. Blood samples were obtained from 398 consecutive patients in the Coronary Care Unit at a hospital in the Netherlands; samples were analyzed for serum antibody levels to H. pylori infection. Questionnaires were sent 2 weeks after discharge to assess GI symptoms. Questionnaires were returned by 314 patients (79 percent). A total of 183 out of 314 patients (46 percent) reported GI symptoms. Of the 238 patients using 80 to 100 milligrams of aspirin daily, 145 (61 percent) recorded GI symptoms. Besides aspirin, the use of calcium antagonists was correlated with GI symptoms. Of the 128 patients using calcium antagonists, 84 (66 percent) reported GI symptoms. The prevalence of GI symptoms in H. pylori positive and negative patients using aspirin was 48 percent and 52 percent respectively. The authors conclude that 2 weeks after discharge, almost 50 percent of the patients with cardiovascular disease experienced GI symptoms, especially patients using aspirin or calcium antagonists. Patients seropositive for H. pylori and using aspirin or calcium antagonists did not have more GI discomfort compared to non infected patients. 2 tables. 16 references. •

Review Article: Have We Found the Source of Helicobacter Pylori? Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 7-12. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Besides the well established Helicobacter pylori reservoir (i.e., the human stomach), numerous other sources of the bacteria have been hypothesized. This article explores the research into the source of H. pylori. The authors note that none of the hypothesized sources have been proven. In some instances (e.g., pig, sheep), Helicobacter species closely related but different from H. pylori were detected, but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (in cats), but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies, which theoretically can be a vehicle (for bacteria transmission) but practically speaking are not because of too few viable bacteria present in feces. Molecular epidemiology studies demonstrating the route of transmission (fecal-oral, oral-oral, or gastro-oral) are still lacking, but recent studies have confirmed the presence of viable H. pylori in vomitus and in feces in the event of diarrhea. 44 references.

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Evaluation of Five Commercial Serological Tests for the Detection of Helicobacter Pylori Infection in Chinese Source: Alimentary Pharmacology and Therapeutics. 15(5): 703-706. May 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Commercial serological (blood) tests for the detection of Helicobacter pylori infection must be locally validated. This article reports on a study that evaluated the accuracy of five commercial tests in the Chinese population. Serum samples were

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collected from patients referred for upper endoscopy. Antral (stomach) biopsies were taken for histological examination and culture of H. pylori. The gold standard for diagnosing H. pylori infection was positive histological staining and or positive H. pylori culture. The serum samples were tested for H. pylori antibodies using the following tests: Cobas Core Anti H pylori EIA; GAP IgG; GAP IgM; H. pylori microwell EIA (Quidel); and Premier H. pylori. The sensitivity, specificity, and accuracy of each test was calculated according to the manufacturers' instructions or according to a new cut off value. A total of 158 patients were recruited among whom 114 (72 percent) were H. pylori positive. Indeterminate results varied from 7 to 19 percent. The accuracy of the tests varied from 57 to 85 percent. By using new cut off values, the accuracy was much improved, ranging from 73.4 percent to 86.7 percent. The authors conclude that by defining new cutoff values for the Chinese population, the researchers were able to improve the performance of some of the serology tests. This illustrates the importance of local validation. 3 tables. 13 references. •

Helicobacter Pylori Eradication Does Not Worsen Quality of Life Related to Reflux Symptoms: A Prospective Trial Source: Alimentary Pharmacology and Therapeutics. 16(6): 1143-1148. June 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Concern has been raised that drug therapy to eradicate Helicobacter pylori infections may lead to the development of gastroesophageal reflux disease (GERD). This article reports on a prospective study that was designed to assess reflux-related quality of life and the symptoms of GERD in patients undergoing H. pylori therapy. Patients with a primary complaint of dyspepsia (upper abdominal pain or discomfort) and endoscopic biopsy positive for H. pylori received triple therapy for 2 weeks. In 48 of 61 patients, H. pylori was eradicated. The mean scores in cured patients for each of the five domains were comparable at baseline and 6 months after therapy. The proportion of cured patients with a large decrease in quality of life (10 to 17 percent) was similar to the proportion with a large increase (15 to 21 percent). Heartburn was present at baseline in 22 cured patients; at 6 months, it persisted in 13 and resolved in 9, while 9 patients developed new heartburn. The authors conclude that a population of patients presenting with dyspepsia should have no overall increase or decrease in quality of life due to symptomatic gastroesophageal reflux disease in the 6 months after H. pylori therapy. 2 tables. 25 references.

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Helicobacter Pylori Eradication: Comparison of Three Treatment Regimens in India Source: Journal of Clinical Gastroenterology. 28(4): 348-351. June 1999. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: Conventional bismuth based triple therapy for Helicobacter pylori has multiple problems, such as inadequate drug compliance, side effects, and drug resistance. The combination of omeprazole and clarithromycin with or without antibiotics like amoxycillin has been shown to be effective in eradicating H. pylori. Reports from India on the efficacy of clarithromycin based drug combinations are few. This article reports on a study that evaluated the efficacy of omeprazole and clarithromycin with or without amoxycillin for treating H. pylori infection. The study comprised 64 consecutive patients with upper gastrointestinal symptoms and H. pylori

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infection. In every patient, complete upper gastrointestinal endoscopy was done. H. pylori infection was diagnosed by identification of organism on antral biopsies and by positive rapid urease test. Patients were treated with omeprazole 40 milligrams per day and clarithromycin 250 milligrams twice daily (group I, n = 22), or omeprazole 40 milligrams per day and clarithromycin 250 milligrams twice daily and amoxycillin 500 milligrams three times daily (group II, n = 20), or bismuth subcitrate 120 milligrams four times daily and amoxycillin 500 milligrams three times daily and metronidazole 400 milligrams three times daily (group III, n = 22) for 2 weeks. H. pylori status was reevaluated 1 month after completion of treatment. One patient in each group stopped taking the drugs because of side effects. The eradication rate was not significantly different in group I (68 percent), group II (70 percent), and group III (59 percent). Of those completing therapy, side effects were observed in three patients in group III (nausea, skin rash, metallic taste), whereas none of the patients in group I and group II had any side effects. Addition of amoxycillin did not appear to improve efficacy of dual omeprazole and clarithromycin therapy, and this combination appeared to be no different from bismuth, metronidazole, and amoxycillin triple therapy. The authors conclude that, overall, none of the regimens was particularly good. 1 table. 28 references. (AA). •

13 C-Urea Breath Test Without a Test Meal Is Highly Accurate for the Detection of Helicobacter Pylori Infection in Chinese Source: Alimentary Pharmacology and Therapeutics. 14(10): 1353-1358. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Conventional C-urea breath testing (13CUBT) includes a test meal to delay gastric emptying, which, theoretically, improves the accuracy of the test. Citric acid has been proposed as the best test meal. However, recent studies have suggested that a test meal may not be necessary. This article reports on a study undertaken to investigate a new 13CUBT protocol without a test meal, in a population of Chinese persons. Consecutive patients with dyspepsia referred for upper endoscopy were recruited for the study (n = 202). 13CUBT was performed on two separate days with or without a test meal (2.4 grams citric acid) and compared with the 'gold standard' (CLO test and histology). Using receiver operating characteristics (ROC) analysis, the optimal delta value and optimal measurement interval for UBT were 5 percent and 30 minutes, respectively, with or without a test meal. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 13CUBT were similar with and without the test meal. The authors conclude that this simplified 13CUBT protocol without a test meal produced highly accurate and reliable results in the Chinese population. 2 figures. 2 tables. 29 references.

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Modified Seven-Day, Quadruple Therapy as a First Line Helicobacter Pylori Treatment Source: Alimentary Pharmacology and Therapeutics. 15(7): 1061-1065. July 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Cure rates of 7 day, triple drug therapy undertaken to treat Helicobacter pylori infections seem to be decreasing. Quadruple therapies may be an alternative,

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although their complex administration makes patient acceptance difficult. This article reports on a study undertaken to test the usefulness of a thrice a day, quadruple therapy to cure H. pylori infection. A total of 122 consecutive patients with peptic ulcer and H. pylori infection were treated with omeprazole 20 milligrams twice daily (b.d.), tetracycline chlorhydrate 500 milligrams thrice daily (t.d.s.), metronidazole 500 milligrams t.d.s., and bismuth subcitrate 120 milligrams t.d.s., administered with meals for 7 days. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. Seven patients were lost to followup. Of the remaining 115, 110 were cured at the first control, giving an intention to treat cure rate of 90.2 percent and a per protocol cure rate of 95.7 percent. All but pne of 103 patients who returned for a 6 month breath test were cured. Side effects were minimal or minor in 47 patients (40.8 percent) and moderate in four (3.4 percent). Compliance was good; 95 percent of patients took more than 90 percent of the pills. Six (5 percent) patients stopped treatment after 1, 2, 4 (two patients), and 6 (two patients) days. The authors conclude that thrice a day quadruple therapy shows excellent cure rates, far above 90 percent, and is well tolerated and easy to comply. Head to head comparison with triple therapies as first line H. pylori treatment seems warranted. 1 table. 32 references. •

Evaluation of Invasive and Non-Invasive Tests for the Diagnosis of Helicobacter Pylori Infection in Chinese Source: Alimentary Pharmacology and Therapeutics. 15(4): 505-511. April 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Different tests are available for diagnosing Helicobacter pylori (a bacterium) infection. This article reports on a study undertaken to compare the most commonly used tests either alone or in combination in Chinese patients with respect to routine clinical use or research purpose. A total of 294 consecutive patients with dyspepsia without previous H. pylori treatment were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus of the stomach, for a commercially available CLO test, an in house rapid urease test, culture, polymerase chain reaction (PCR), and histological examination. Patients then received a 13C urea breath test. The H. pylori status of each patient was determined by a concordance of test results. For routine clinical use, histology (examination of the cells from antral plus corpus biopsies) had an accuracy of 100 percent, while the rapid urease test had an accuracy of 99.7 percent. The 13C urea test was equally reliable, with an accuracy of 94.5 percent. Combinations of two tests did not confer additional advantage over the most accurate single test. For research purposes, the accuracy of using the criteria of two positives out of three diagnostic tests was 100 percent and equivocal results were not found. 2 tables. 23 references.

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Treatment of Helicobacter Pylori in Patients with Upper Abdominal Pain Syndromes Source: Canadian Journal of Gastroenterology. 13(4): 299-300. May 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Summary: Dyspepsia has been defined as a syndrome of upper abdominal pain that is endoscopy negative (i.e., no ulcer). The cause of this syndrome is not clear, but it is believed that it may be heterogeneous; to date, no cause has been elucidated, but some investigators believe that Helicobacter pylori might be important. This article

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summarizes three recent research studies that investigated the role of H. pylori eradication in the treatment of upper abdominal pain syndromes. Despite the differences in design among the three studies, similar conclusions were reached by the investigator. In once, a treatment regimen designed to eradicate H. pylori had only a marginal impact, at best, on symptoms, while the other two studies did not demonstrate a convincing benefit. The author hypothesizes that perhaps the minor differences in the results obtained between the first study and the other two studies related largely to the definition of dyspepsia, differences in scoring systems, and possibly some of the endoscopic criteria for 'normal.' The author concludes that these studies may not have an impact on the prescribing practice of the clinical gastroenterologist. However, the results may give pause to empiricists who feel obliged to treat patients with upper abdominal pain syndromes and no defined cause with a costly pharmaceutical regimen of multiple antibiotics and proton pump inhibitors. 3 references. •

Immunology of Helicobacter Pylori and Prospects for Vaccine Source: Gastroenterology Clinics of North America. 29(3): 671-685. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Effective antimicrobial therapies have been developed to treat Helicobacter pylori infections; however, patient compliance with a complicated regimen that can cause unpleasant side effects has been less than ideal. An efficacious vaccine against Helicobacter pylori would provide a cost effective means of preventing numerous gastric diseases. This article reviews the immunology of H. pylori and prospects for a vaccine. Several H. pylori animal models have been developed for use in the development of prototype subunit H. pylori vaccines. Using murine (mouse), ferret, and nonhuman primate systems, prophylactic and therapeutic vaccines have been shown to be effective at providing protection or in significantly reducing the H. pylori load in the gastric mucosa. Many of these vaccine prototypes have been delivered orally. Recent studies investigating alternative routes of antigen delivery and more traditional adjuvant systems provide encouraging data that a vaccine might someday be extended for use in humans. A better understanding of the host immune response to H. pylori infection should allow investigators to develop immunotherapies to prevent the acquisition of infection and eradicate existing chronic H. pylori infection. 1 figure. 1 table. 85 references.

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Comparative Efficacy of New Investigational Agents Against Helicobacter Pylori Source: Alimentary Pharmacology and Therapeutics. 15(4): 487-492. April 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Emergence of antibiotic resistant Helicobacter pylori (a bacterium) has necessitated the identification of alternate therapies for the treatment of this infection. This article reports on a study undertaken to assess the in vitro (in real life use) of two agents still under investigation: DMG-MINO CL 344 (a derivative of minocycline) and davercin, a cyclic carbonate of erythromycin A. These agents were compared to older antibiotics (clarithromycin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, and cefixime) against clinical isolates of H. pylori. Testing was performed using the agar dilution method; Mueller Hinton agar containing 5 percent aged sheep blood was used. Twenty-one clarithromycin resistant and 16 clarithromycin susceptible

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clinical isolates of H. pylori, obtained from patients with duodenal ulcer, were used. Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective. Against clarithromycin resistant H. pylori, the values showed that the tetracyclines and cefixime were the most effective agents. The fluoroquinolones and macrolides were ineffective. Macrolide cross resistance was detected. The authors conclude that macrolide cross resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present. Tetracyclines and cefixime are possible alternative agents for the treatment of H. pylori infection in these patients. 2 tables. 33 references. •

One-Week Triple Therapy with Esomeprazole Provides Effective Eradication of Helicobacter Pylori in Duodenal Ulcer Disease Source: Alimentary Pharmacology and Therapeutics. 14(12): 1605-1611. December 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid related diseases. This article reports on a study of 1 week triple therapy with esomeprazole for eradication of Helicobacter pylori bacteria in duodenal ulcer disease. Patients with H. pylori infection, confirmed by C urea13 breath test (UBT), and no current ulcer, were randomized to double blind treatment with esomeprazole 20 mg twice daily (n = 224) or omeprazole 20 mg twice daily (n = 224), in combination with amoxicillin 1 gram twice daily and clarithromycin 500 mg twice daily for 1 week. A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication. Between group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy. The most commonly reported adverse events were diarrhea and taste changes, which were most likely attributable to amoxicillin and clarithromycin, respectively. The 90 percent eradication rate exceeds that of current recommendations and national guidelines. 4 figures. 3 tables. 17 references.

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Helicobacter Pylori 'Rescue' Regimen When Proton Pump Inhibitor-Based Triple Therapies Fail Source: Alimentary Pharmacology and Therapeutics. 16(6): 1047-1057. June 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Even with the currently most effective treatment regimens, about 10 to 20 percent of patients will fail to obtain eradication of Helicobacter pylori infection. Therefore, in designing a treatment strategy, physicians should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. This review article focuses on rescue regimens undertaken in patients when the standard triple combinations of drugs (proton pump inhibitor plus two antibiotics) fail. The authors note that the choice of second line treatment depends on which treatment was used initially, because re-treatment with the same regimen is not recommended. Therefore, it is not necessary to perform culture after the first eradication failure. Assessment of the severity of H. pylori to antibiotics is suggested only after failure of the second treatment. Different possibilities of empirical treatment have been suggested. After failure of

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proton pump inhibitor-amoxicillin-clarithromycin therapy, quadruple therapy has generally been used. More recently, replacement of the proton pump inhibitor and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After proton pump inhibitor-amoxicillin-nitromidazole failure, re-treatment with proton pump inhibitor-amoxicillin-clarithromycin has been proven to be effective. Finally, first line treatment should not combine clarithromycin and metronidazole in the same regimen, because of the problem of resistance to both antibiotics. Recently, rifabutinbased rescue therapies have been shown to constitute an encouraging strategy for eradication failures, as they are effective against H. pylori strains that are resistant to antibiotics. 1 figure. 1 table. 70 references. •

Gastric Outlet Obstruction Resulting from Peptic Ulcer Disease Requiring Surgical Intervention Is Infrequently Associated with Helicobacter Pylori Infection Source: Journal of the American College of Surgeons. 191(1): 32-37. July 2000. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: Gastric outlet obstruction (GOO) secondary to peptic ulcer disease (PUD) requiring therapeutic intervention remains a common problem. The incident of Helicobacter pylori infection in this cohort has not been well defined. Pneumatic dilation (PD) has been proposed as first line therapy before surgical intervention. If H. pylori infection in patients with GOO is infrequent, PD may not offer permanent control without the need for long term antacid therapy. This article reports on a study undertaken to examine the incidence of H. pylori infection and surgical outcomes in patients undergoing resection for GOO. The records of all patients having resection (vagotomy and antrectomy) for benign disease from 1993 to 1998 for GOO at the University of Tennessee hospitals were reviewed retrospectively. Smoking history, NSAID use, weight loss, previous ulcer treatment, previous treatment for H. pylori, and previous attempts at PD were among the factors examined. Surgical complications and patient satisfaction were ascertained from inpatient records, postoperative clinical notes, and followup telephone surveys. During the study period, 24 patients underwent surgical resection. There were 16 men and 8 women, with a mean age of 61 years (range 40 to 87 years). Weight loss was documented in 58 percent and averaged 27 pounds. Five of 24 patients had previous attempts at PD, 3 of whom were H. pylori negative. All five had further weight loss after these failed attempts. Of the 24 patients reviewed, only 8 (33 percent) were H. pylori positive. There were no procedure related deaths. Long term clinical followup was possible in 16 of 24 patients, and all but one demonstrated dramatic clinical improvement by Visick score. The authors concluded that patients with H. pylori negative GOO resulting from peptic ulcer disease should be strongly considered for an early, definitive, acid reducing surgical procedure. 1 figure. 3 tables. 22 references.

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Are Genetic Influences on Peptic Ulcer Dependent or Independent of Genetic Influences for Helicobacter Pylori Infection? Source: Archives of Internal Medicine. 160(1): 105-109. January 10, 2000. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10946, Chicago, IL 60610-0946. (800) 262-2350. Fax (312) 464-5831. E-mail: [email protected]. Summary: Genetic factors play a role or roles in the etiology (cause or development) of peptic ulcer disease (PUD) and the acquisition of Helicobacter pylori infection. This

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article reports on a study undertaken to evaluate the relative importance of genetic and environmental influences as well as the importance of H. pylori on PUD. The cross sectional study included monozygotic (MZ) and dizygotic (DZ) twins, reared apart or together. A total of 258 twin pairs had information regarding H. pylori status and history of peptic ulcer. The intraclass correlations for PUD for MS twins reared apart and together and DZ twins reared apart and together were 0.67, 0.65, 0.22, and 0.35, respectively, which indicates that genetic effects are important for liability to peptic ulcer. The correlation coefficient for MZ twins reared apart (0.67) provides the best single estimate of the relative importance of genetic effects (heritability) for variation in liability to peptic ulcer disease, and structural model fitting analyses confirmed this result. The cross twin cross trait correlations for MZ and DZ twins were examined to determine whether genetic effects for peptic ulcer were shared with or independent of genetic influences for H. pylori. The results suggested that familial environmental rather than genetic influences mediate the association between PUD and H. pylori infection. The authors conclude that genetic influences are of moderate importance for liability to peptic ulcer disease. 3 tables. 33 references. •

Improvement in Atrophic Gastritis and Intestinal Metaplasia in Patients in Whom Helicobacter Pylori Was Eradicated Source: Annals of Internal Medicine. 134(5): 380-386. March 6, 2001. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Glandular atrophy and intestinal metaplasia (changes in the cells of the intestinal lining) are precancerous lesions; whether Helicobacter pylori infection or its eradication affects these lesions is controversial. This article reports on a study undertaken to determine whether eradication of H. pylori is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. The single blind prospective trial included 163 consecutive patients with dyspepsia and H. pylori infection, seen at an academic gastroenterology clinic in Japan. The intervention consisted of a 1 week course of a proton pump inhibitor and antibiotic therapy. In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus (the main body of the stomach) and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 of 38 patients (89 percent) with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 of 46 patients (61 percent) who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. The authors conclude that in the year after successful H. pylori eradication, precancerous lesions improved in most patients. 1 figure. 1 table. 20 references.

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Helicobacter Pylori and Nonsteroidal Anti-Inflammatory Drugs Source: Gastroenterology Clinics of North America. 30(4): 937-952. December 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) cause most peptic ulcer disease. Because both of these factors are highly prevalent, defining the precise relationship between H. pylori and NSAIDs is important for theoretical and practical reasons. To date, there are data to suggest that H. pylori

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increases, has no effect on, or decreases ulcer risk in NSAID users. This confusion reflects a complex relationship between H. pylori and NSAIDs. The complexity is due partly to a wide spectrum of host response to H. pylori and NSAIDs. This article gives an overview of the pathogenetic mechanisms shared by H. pylori and NSAIDs on ulcer development, then reviews the clinical studies on the interaction between H. pylori and NSAIDs. The author emphasizes that better understanding of the design of these studies might resolve some of the controversies. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs, and low dose aspirin all affect the interrelationship between H. pylori, NSAIDs, and ulcers. 2 figures. 4 tables. 77 references. •

Relationship Between Persistence of Helicobacter Pylori and Dysplasia, Intestinal Metaplasia, Atrophy, Inflammation, and Cell Proliferation following Partial Gastrectomy Source: Digestive Diseases and Sciences. 44(2): 243-252. February 1999. Summary: Helicobacter pylori and partial gastric resection are risk factors for cancer. This article reports on a study to investigate the presence of H. pylori in postgastrectomy patients and to correlate that with alterations in mucosal architecture and cell proliferation. The study included 151 endoscopic biopsies from 22 patients (15 to 47 years of age, mean age 29.2 years), following partial gastrectomy with Billroth II reconstruction for peptic ulcer disease; each biopsy was examined for the presence of H. pylori using Giemsa staining. Sections were scored for grade of hyperplasia, intestinal metaplasia, dysplasia, inflammation, and atrophy. Immunohistochemistry for proliferative cell nuclear antigen (PCNA) was used to characterize cell proliferation. H. pylori was observed in 17 of 22 patients (77.3 percent) or in 57 of 151 biopsies (37.7 percent). Metaplasia was seen in 18 of the 22, chronic atrophic gastritis in 20 of 22 patients, and cystic glandular dilation in 21 of the 22 patients. The highest type of metaplasia in each patient was: four Type I, five Type IIA and nine Type IIB. Dysplasia was present in 16 biopsies from nine patients. H. pylori was more prevalent in intestinal metaplasia type I (44.8 percent of biopsies), than in type IIA (32.7 percent) or type IIB (25 percent). No H. pylori was detected in regions showing dysplasia or cystic glandular dilation. H. pylori colonization was associated with degree of inflammation and cell proliferation. In conclusion, H. pylori is commonly seen many years after gastrectomy, it is associated with an increased epithelial cell proliferation, and it is not present in areas of histologic markers of premalignancy (type IIB metaplasia and dysplasia). 4 figures. 5 tables. 42 references.

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Evaluation of Helicobacter Pylori Diagnostic Methods in Patients With Liver Cirrhosis Source: Alimentary Pharmacology and Therapeutics. 16(7):1283-1289. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori associated peptic ulcer is a frequent complication in patients with cirrhosis (scarring of the liver) and its morbidity rate (associated illness or disease complications) is high. In spite of this, diagnostic methods for H. pylori infection have not been fully evaluated in these patients. This article reports on a study undertaken to evaluate H. pylori diagnostic methods in patients with liver cirrhosis (n = 101). Results showed that 62 patients were positive for H. pylori and 35 were negative

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for H. pylori infection; four were indeterminate. The sensitivity and specificity were 90.4 percent and 100 percent, respectively, for antral histology; 100 percent and 100 percent for gastric body histology; 90.4 percent and 100 percent for antral immunohistochemistry; 96.2 percent and 96.7 percent for body immunochemistry; 85.7 percent and 97 percent for rapid urease test; 83.6 percent and 55.9 percent for serology; 96.4 percent and 97.1 percent for 13C urea breath test; and 75.4 percent and 94.1 percent for fecal antigen. The authors conclude that the most reliable tests for H. pylori infection in cirrhosis patients were the 13C urea breath test and gastric body histology. 1 figure. 4 tables. 28 references. •

Does Helicobacter Pylori Affect Gastric Mucin Expression? Relationship Between Gastric Antral Mucin Expression and H. Pylori Colonization Source: European Journal of Gastroenterology and Hepatology. 13(1): 19-23. January 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: Helicobacter pylori colonizes the mucous gel layer, the surface epithelium, and the glands of the stomach. It has previously been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum (the passage from the esophagus to the stomach, i.e., the first part of the stomach) of patients with dyspepsia, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori negative patients. There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication. MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. The authors conclude that the change in MUC 5 synthesis may reflect H. pylori colonization. 6 figures. 18 references.

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Fecal and Oral Shedding of Helicobacter Pylori from Healthy Infected Adults Source: JAMA. Journal of American Medical Association. 282(23): 2240-2245. December 15, 1999. Summary: Helicobacter pylori commonly infects humans; however, its mode of transmission remains unknown. This article reports on a study to determine how humans (the primary host for H. pylori) shed the organism into the environment. The controlled clinical experimental study of 16 asymptomatic H. pylori infected adults and 10 uninfected adults was conducted from February through December 1998 in a hospital in northern California. A cathartic (sodium phosphate, which causes defecation) and an emetic (ipecac, which causes vomiting) were given to all infected subjects, and an emetic was given to one uninfected subject. All vomitus samples from infected subjects grew H. pylori, often in high quantities. Air sampled during vomiting grew H. pylori from 6 (37.5 percent) of the 16 subjects. Saliva before and after emesis grew low quantities of H. pylori in 3 (18.8 percent) and 9 (56.3 percent) subjects, respectively. No normal stools

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and only 22 (21.8 percent) of 101 induced stools grew the organism, although 7 (50 percent) of 14 subjects had at least one positive culture (2 stool culture samples were contaminated by fungus and were not included). No samples from uninfected subjects yielded H. pylori. The authors conclude that H. pylori can be cultivated uniformly from vomitus and, occasionally, from saliva and cathartic stools. The organism is potentially transmissible during episodes of gastrointestinal tract illness, particularly with vomiting. 1 figure. 2 tables. 38 references. •

Post-Treatment Diagnostic Accuracy of a New Enzyme Immunoassay to Detect Helicobacter Pylori in Stools Source: Alimentary Pharmacology and Therapeutics. 15(3): 395-401. March 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori has attracted increasing attention among gastroenterologists because of its pathogenic (disease causing) potential, stimulating the search for non invasive diagnostic tests. This article reports on a study undertaken to evaluate the efficacy of a new enzyme immunoassay designed to detect H. pylori antigens in stools (HpSA), before and after eradication therapy. HpSA was performed on stool samples collected from 268 patients whose H. pylori status was defined on the basis of concordant results for the 13C urea breath test, rapid urease test, and histology. The H. pylori positive patients were treated with a 1 week triple therapy to eradicate the infection. One (T30) and 3 months (T90) after the end of therapy. 13C urea breath tests and HpSA were repeated in the treated patients. The overall diagnostic accuracy of HpSA at T30 (83 percent) was significantly lower in comparison to the values obtained at baseline (94 percent) and at T90 (97 percent). No significant difference was found between the diagnostic accuracy of HpSA at baseline and at T90. The authors conclude that these data suggest HpSA provides a low diagnostic accuracy when used shortly after treatment. It needs a longer period of followup (8 to 12 weeks) to reach a reliability comparable to the 13C urea breath test. In regards to the issue of cost effectiveness, the kit and technical support for the HpSA is approximately $27 per test; this cost is higher than serology (blood tests), which cannot be reliably used in the post treatment phase, but lower than the 13C urea breath test, at approximately $50. The authors believe that HpSA can be reasonably included among non invasive tests as an accurate and cost effective alternative to the 13C urea breath test for the pretreatment diagnosis of H. pylori infection; for the assessment of eradication, it can be highly reliable, provided that it is performed 3 months after the end of treatment. 5 figures. 25 references.

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Can Helicobacter Pylori Serology Still Be Applied As a Surrogate Marker to Identify Peptic Ulcer Disease in Dyspepsia? Source: Alimentary Pharmacology and Therapeutics. 14(5): 615-624. May 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori infection and associated peptic ulcer disease (PUD) has become less common in some countries. This article reports on a study undertaken to determine if H. pylori serology alone or combined with a history of ingestion of nonsteroidal antiinflammatory drugs (NSAIDs) and an age threshold can be used as an indirect ulcer test. The patients (n = 250; 121 males, mean age 52 years) were consecutive

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Australian patients referred for endoscopy. At endoscopy, eight biopsies were taken for rapid urease test (CLO) testing, culture, and histology. NSAID use over the prior 3 months was recorded. Results showed that 106 (42 percent) of the patients were seropositive for H. pylori; 48 (19 percent) patients had PUD (peptic ulcer disease), and 30 (12 percent) used NSAIDs. Serology alone had a sensitivity of 52 percent and a specificity of 60 percent for identifying PUD; the sensitivity and specificity were 60 percent and 55 percent, respectively, when combined with a history of NSAID use. Serology, regardless of NSAID use, would have saved 23 percent in endoscopy workload but would have missed 17 percent of PUD cases if an age threshold of less than 45 years was chosen for omitting endoscopy. The authors conclude that serology was a poor ulcer test despite an excellent performance for detecting H. pylori. A strategy combining serology and an age threshold with a history of NSAID use to reduce endoscopy workloads may not always be appropriate. 1 figure. 4 tables. 47 references. •

Update on the Management of Helicobacter Pylori Infection, Including DrugResistant Organisms Source: Journal of Gastroenterology and Hepatology. 17(4): 482-487. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori infection has many different clinical outcomes and not all infected persons need to be treated. Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision making process. This article offers an update on the management of H. pylori infection, including drug-resistant organisms. Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin, is the established treatment of choice. For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin. H. pylori resistance to metronidazole has been reported in up to 80 percent and resistance to clarithromycin in 2 to 10 percent of strains cultured. Resistance to either one of the antibiotics has been reported to result in a drop in effectiveness of up to 50 percent. To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible. For failed treatment, several strategies can be employed. These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs. The author briefly discusses various options for 'rescue' therapies for patients who are refractory to treatment. 2 tables. 41 references.

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Long-Term Effects of Cure of Helicobacter Pylori Infection on Patients with Atrophic Body Gastritis Source: Alimentary Pharmacology and Therapeutics. 16(10): 1701-1708. October 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori infection induces atrophic body gastritis (chronic inflammation of the stomach, associated with degeneration of the stomach mucosa), but the long-term effect of its cure on body atrophy is unclear. This article reports on a study undertaken to investigate the long term effects of H. pylori cure on gastric (stomach)

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morpho-functional parameters in patients with atrophic body gastritis. Forty patients with atrophic body gastritis were cured of H. pylori infection. At eradication assessment (6 to 12 months), in eight of the 40 patients, body atrophy was no longer observed, whereas in 32 of the 40 it remained substantially unchanged. In the 8 patients with reversed body atrophy, gastrinemia decreased significantly with respect to pretreatment values, and basal and stimulated acid secretion increased significantly after cure. In the 32 patients still presenting body atrophy, gastrinemia was similar to pretreatment values. At follow up, the eight patients with revered body atrophy continued with normal gastrinemia, but in the 19 patients with continued atrophy, both corporal atrophy and intestinal metaplasia remained substantially unchanged. The authors conclude that following successful treatment in patients with atrophic body gastritis and H. pylori infection, long-term histological investigations are crucial in order to detect reversed body damage or to confirm continued body atrophy. 4 figures. 2 tables. 35 references. •

Virulence and Pathogenicity of Helicobacter Pylori Source: Gastroenterology Clinics of North America. 29(3): 649-670. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Helicobacter pylori infection is associated with multiple gastroduodenal (stomach and duodenum) disease manifestations. This article reviews many of the bacterial and host factors important in these diseases. The role of conserved and nonconserved H. pylori genes, genotyping, and effect on the epithelial cell cycle in the pathogenesis of disease are discussed. The authors also summarize the alteration of host physiological and immune response mechanisms and the molecules involved in the inflammatory cascade. Virulence (how strong it is and how much it affects the host) of H. pylori is based on factors that allow colonization and adaptation to the stomach environment, and the stimulation of mediators of inflammation that contribute to the physiologic and histologic (cell) changes that happen in the host (infected person). The complete DNA sequences for two H. pylori strain genomes have been published; however, whether these two DNA sequences are sufficient representation of the diversity of H. pylori genetics is unknown. The authors conclude that a better understanding of the role of H. pylori in apoptosis (sloughing off of mucosa) and cellular proliferation would enable clinicians to understand the bacterium's relationship to ulcer generation and stomach cancer. The development of animal models with H. pylori and other Helicobacter species has set the stage in which in vitro observations can be tested in the in vivo model. 1 figure. 1 table. 109 references.

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Bismuth-Based Multi-Drug Therapies in Helicobacter Pylori Eradication Source: Today's Therapeutic Trends. 18(3): 229-239. Third Quarter, 2000. Contact: Available from Communications Media for Education, Inc. P.O. Box 712, Princeton Junction, NJ 08550. (800) 221-3899 or (609) 799-2300. Fax (609) 275-8745. Summary: Helicobacter pylori infection of the gastric mucosa (stomach lining) causes progressive damage, with impairment of gastric function. In the United States, the presence of H. pylori infection has been shown to carry a lifetime risk of peptic ulcer disease of at least 16 percent and a 1 to 3 percent lifetime risk for gastric (stomach) cancer. Numerous treatment regimens have been used to eradicate H. pylori infection. As the organism readily develops antibiotic resistance to single antibiotics, development of multiple drug treatment regimens occurred. Bismuth containing triple therapies were

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the first treatment approach to prove successful, and they are the focus of this review article. Successful therapies have used both topical and systemic antimicrobials. The combination of a proton pump inhibitor (PPI), clarithromycin and amoxicillin; and the bismuth, metronidazole, tetracycline (BMT) combinations, are both available in convenient dose packs (Prevac and Helidac, respectively) that enhance patient acceptance and compliance. The BMT combinations offer a significant cost advantage. The authors conclude that bismuth compounds are safe and effective, and significant H. pylori resistance has not been described. The increasing incidence of clarithromycin resistance suggests that therapies containing bismuth will continue to be a cornerstone of anti H. pylori therapy. 1 table. 32 references. •

Current Therapy for Helicobacter Pylori Infection in Children and Adolescents Source: Canadian Journal of Gastroenterology. 13(7): 571-579. September 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: Helicobacter pylori infects approximately 50 percent of the world's population and is a definitive cause of gastroduodenal disease (i.e., gastritis, duodenal and gastric ulcers) in children and adults. At each of four international conferences, the objective was to reach a consensus on the development of practical guidelines for the diagnosis and treatment of H. pylori infected individuals. However, it was not until the Canadian H. pylori Consensus Conference, held in November 1997, that the issues of H. pylori infection in children were addressed. This article reviews therapies for H. pylori infection in children. If it is accepted that gastric colonization by H. pylori is associated with pediatric gastroduodenal disease, then eradication of the organism must be the intent of the practitioner caring for the child infected with H. pylori. An ideal treatment for H. pylori in children has yet to be determined. This is due to problems with antibiotic resistance, a lack of research treatment trials conducted in children, and problems with drug side effects. Current H. pylori eradication therapy recommendations have been made by extrapolating findings from adult studies in combination with data available from small case series reported in pediatric patients. One chart offers six potential treatment options for H. pylori infections in children. Dual therapy containing regimens are not included as options, due to the clear superiority of triple therapy containing regimens. 5 tables. 87 references.

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Diagnosing and Managing H. Pylori Infections Source: IM. Internal Medicine. 19(7): 10-20, 25. July 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: Helicobacter pylori is a bacteria that thrives in the acidic environment of the stomach, living in the mucous layer covering the gastric mucosa. This continuing education article updates physicians on the latest techniques for diagnosing and managing H. pylori infections. H. pylori has been strongly associated with gastritis, duodenal ulcers, gastric ulcers, and both gastric adenocarcinoma and gastric lymphoma. Diagnostic tests to determine if a patient is infected with H. pylori fall into two categories: noninvasive and nonendoscopic, or invasive and endoscopic tests. Diagnostic tests that do not require endoscopy include various methods of antibody detection and carbon-labeled urea breath tests. Those that involve endoscopy are the rapid urease tests, histology, and culture. The author stresses that the decision to test for H. pylori must be made with a firm resolve to proceed with treatment if the patient is

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infected. Treating H. pylori-positive duodenal and gastric ulcers produces a definitive benefit and is considered the standard of care. Furthermore, successful bacterial cure almost completely eliminates the risk of recurrent bleeding from gastric or duodenal ulcers. Even in patients who take NSAIDs (nonsteroidal anti-inflammatory drugs), H. pylori should be considered an important independent risk factor for ulcer recurrence and should therefore be treated. The author notes that complications of treatment regimens for H. pylori are usually mild and may include nausea, diarrhea, altered sense of taste, and vaginitis. Sidebars present four brief case histories, and their management. The article includes a recertification review self-test; the answers appear in the same journal issue. 4 tables. 19 references. •

Low Rates of Helicobacter Pylori Reinfection in Children Source: Gastroenterology. 117(2): 336-341. August 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Helicobacter pylori is a bacterium that causes gastritis and is associated with duodenal ulcer disease in adults and children. Reinfection after treatment for H. pylori infection is uncommon in adults. It is more likely to occur in children because they acquire primary infection. This article reports on a study to determine whether children are likely to become reinfected with H. pylori and if there are any risk factors for reinfection. The prospective study included 52 children. Children, parents, and siblings underwent 13C urea breath tests. Details of family size and socioeconomic status were documented. The duration of followup was 103.8 patient years (mean was 24 months). Forty six (88.5 percent) of the index children remained clear of infection, and 6 (11.5 percent) children were reinfected. The mean age of those who became reinfected was 5.8 years (plus or minus 5.6 years) compared with 12.3 years (plus or minus 3.0 years) for those who remained clear of infection. Only 2 of 46 (4.3 percent) children older than 5 years of age were reinfected, although 80.8 percent had 1 infected parent and 65 percent of siblings were infected. Reinfection rate was 2.0 percent per person per year in children older than 5 years. Living with infected parents and siblings and low socioeconomic status were not risk factors for reinfection. In logistic regression analysis, age was the only risk factor for reinfection. The authors conclude that these findings also indicate that it is not necessary to treat all family members to achieve long term eradication of H. pylori. 1 figure. 3 tables. 33 references.

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Helicobacter Pylori and Clinical Risks: Focus on Gastro-Oesophageal Reflux Disease Source: Alimentary Pharmacology and Therapeutics. 16 (6 Supplement 3): 1-10. June 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori is a stomach (gastric) pathogen that is a major cause of peptic ulcer disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma, and is associated with gastric cancer. Yet, in a large proportion of the human population, H. pylori infection has no apparent adverse clinical consequences. Furthermore, recent research suggests that H. pylori may even confer protection against gastroesophageal reflux disease (GERD). This article summarizes a sponsored symposium held in Helsinki. The symposium was introduced by Professor P. Malfertheiner, with papers presented by Dr. H. J. O'Connor, Professor R.M. Genta, Dr.

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P. Unge, and Professor A.T.R. Axon. Emerging epidemiological and retrospective evidence suggests that the presence of H. pylori infection may provide some protection against GERD, but there is other evidence that shows no benefit of H. pylori for the protection of the esophagus. The presenters emphasize that prospective, multicenter studies are needed to explore the H. pylori-GERD relationship further, to avoid confusing potential benefits with known risks. 58 references. •

Recent Developments in the Epidemiology of Helicobacter Pylori Source: Gastroenterology Clinics of North America. 29(3): 559-578. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: Helicobacter pylori is found commonly throughout the world irrespective of how exotic the location. H. pylori remains among the most universal of infections; however, the understanding of some features of infection has changed. This review article on the epidemiology of Helicobacter pylori updates previous reviews and focuses on information made available in the last few years. Several studies of H. pylori have examined identification of new infections and loss of existing infections over time. These studies bring additional information to the many studies on prevalence, however, direct evidence of the major routes of transmission is still lacking. Oral oral, and oral fecal infection has declined rapidly in developed countries, which probably has contributed to declines in duodenal ulcer disease and gastric cancer. Apart from studies of transmission, the influence of H. pylori infection on upper gastrointestinal diseases is undergoing reappraisal. The author notes that the full health implications of the potential elimination of infection are unknown. 2 figures. 2 tables. 143 references.

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Gastritis and Helicobacter Pylori: Forty Years of Antibiotic Therapy Source: Digestion. 58(3): 203-210. May-June 1997. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. Summary: Helicobacter pylori is now at the forefront of gastroenterology, particularly regarding its eradication as the treatment of gastroduodenal ulcer, whereas its role in gastritis is still widely ignored. The author notes that gastritis was the disease for which H. pylori was originally studied. This article reviews the 40 years of antibiotic therapy for gastrointestinal diseases, notably gastritis, and the application of this experience to present considerations for treatment. Forty years ago, it was shown for the first time that antibiotics can eliminate gastric ammonia production in humans; this suggested that this was due to eradication of bacterial urease activity. Researchers also found that the gastric juice ammonia concentration correlates with hypoacidity (low acid levels) or anacidity (no acid) in people with uremia and with mucosal inflammation in subjects with gastritis. In patients with nonalcoholic and alcoholic gastritis, the histology as well as the symptoms of gastritis were strikingly improved by antibiotic treatment. The beneficial effects of eradication of gastric urease activity and the resulting decreased ammonia production were also shown in patients with hepatic encephalopathy. The author concludes by emphasizing that broader studies and clinical applications of these earlier findings are now warranted. 7 figures. 62 references. (AA-M).

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13C-Urea Breath Tests are the Noninvasive Method of Choice for Helicobacter Pylori Detection Source: Canadian Journal of Gastroenterology. 13(8): 681-683. October 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: Helicobacter pylori is recognized as the most important cause of duodenal and gastric ulcers. This article describes the use of the 13C urea breath test for the noninvasive identification of H. pylori infection. The 13C UBT is more accurate than serology (blood tests) with better positive and negative predictive values, is nonradioactive and safe, and can be used to diagnose H. pylori noninvasively both before and after eradication treatment. The test is simple to administer and can be done anywhere. It is particularly more effective in the under 50 years age group in which the 'test and treat' strategy is advocated. Thus, practitioners can conveniently identify patients who are truly positive for H. pylori, and treatment with antibiotics can be given appropriately. As such, the 13C UBT is advocated as the only reliable nonendoscopic means of detecting H. pylori. The authors conclude that, given the need for this test, it should be made more widely available, and reimbursement should be provided by health care plans. 2 figures. 27 references.

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Treatment of Helicobacter Pylori: An Overview Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 1-6. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Helicobacter pylori is recognized to be a serious pathogen, but there is still controversy as to who should be treated. This article reviews the arguments and some of the data advanced to support the differing views; the author briefly considers the currently used therapies and how they may best be employed. There is consensus for treatment of patients with H. pylori positive peptic ulcer and B cell lymphoma. Patients with lymphcytic gastritis and giant fold gastritis (Menetrier's disease) may also respond to treatment. Patients with functional dyspepsia have a 20 percent placebo response with a 5 to 10 percent 'eradication' response, results not dissimilar from empirical treatment with a proton pump inhibitor (PPI). A 'test and treat' policy for patients with uninvestigated dyspepsia remains controversial. Some clinicians have suggested that eradication of the H. pylori may increase the patient's risk of gastroesophageal reflux disease (GERD) or predispose patients to adenocarcinoma at the gastroesophageal junction (stomach cancer). However, PPI treatment without H. pylori eradication induces greater inflammation in the gastric corpus; this is the phenotype associated with non-cardia gastric cancer. A minority of clinicians believe the H. pylori should be eradicated in all individuals. The author concludes that, when choosing treatment, it is logical to start with a combination of antibiotics that, in the event of failure, will allow a second combination to be used without overlap. The author recommends the use of amoxycillin, clarithromycin, and a PPI for the first treatment, which then leaves the option of ranitidine bismuth citrate, tetracycline, and metronidazole, in the event of first line failure. 37 references.

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Helicobacter Pylori: An Emerging Infectious Disease Source: Nurse Practitioner. 25(8): 40, 43-44, 47, 50, 53-55. August 2000. Contact: Available from Nurse Practitioner. Circulation Department, P.O. Box 5053, Brentwood, TN 37024-5053. (800) 490-6580. Fax (615) 377-0525. Summary: Helicobacter pylori is the most common chronic bacterial infection in the world, colonizing the stomachs of more than 50 percent of the human population. The discovery of this bacterium has changed the concept of care and management for peptic ulcer disease (PUD), mucosa associated lymphomas, gastritis, and gastric carcinoma (stomach cancer). Although the mode of transmission is not definitively known, person to person contact is suspected. This article discusses H. pylori, the associated clinical syndromes and diseases, risk factors, and current pharmacologic management. In the United States, H. pylori prevalence increases by 10 percent with each decade of life. The infection is more prevalent in groups of lower socioeconomic status. Crowded living conditions, such as in institutions, increase the incidence and prevalence. Controversy exists regarding testing patients for H. pylori who present with complaints consistent with dyspepsia. Those who should be tested for H. pylori include patients who have a history of PUD and have not been treated for H. pylori in the past, and patients with a history of MALT lymphoma. A recent report suggests screening patients with a parental history of gastric cancer. For outpatient diagnosis, serology or a urea breath test can be used with high sensitivity and relatively low cost. A variety of treatment protocols may be used to eradicate H. pylori; however, only two are currently approved by the Food and Drug Administration. One regimen consists of amoxicillin, clarithromycin, and omeprazole for 14 days; the second regimen uses amoxicillin, clarithromycin, and lansoprazole for 10 days. Reinfection rarely occurs after successful treatment of H. pylori. A posttest with which readers can quality for continuing education credits is appended to the article. 3 figures. 2 tables. 44 references.

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Overexpression of Co-Stimulatory Molecules in Peripheral Mononuclear Cells of Helicobacter Pylori-Positive Peptic Ulcer Patients: Possible Difference in Host Responsiveness Compared With Non-Ulcer Source: European Journal of Gastroenterology and Hepatology. 13(1): 11-18. January 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: Helicobacter pylori is the principal cause of gastritis and peptic ulcer disease. However, H. pylori positive patients do not always have peptic ulcer. This study was carried out in order to determine the difference in host immune reaction to H. pylori between patients with peptic ulcer and those without. The study included 10 H. pylori positive patients with peptic ulcer, 10 H. pylori positive nonulcer patients, and 10 healthy volunteers who were examined for expression of surface molecules in peripheral blood mononuclear cells. The results showed more mononuclear cells expressed molecules ICAM-1, VLA-4, Leu-M3 in H. pylori positive ulcer patients than in nonulcer patients and healthy volunteers. There were also more cells expressing CD28, SLex, CD4, HLA-DR, and NU-B2 in H. pylori positive ulcer patients than in nonulcer patients and healthy volunteers. There were fewer cells expressing CD8 in H. pylori positive ulcer patients than in nonulcer patients and healthy volunteers. The authors conclude that H. pylori infection may cause immunological reactions which are reflected in peripheral mononuclear cells. However, the activity and characteristics of

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peripheral mononuclear cells, in terms of expression of adhesion molecules, may differ between ulcer and nonulcer patients who are infected with H. pylori. 8 figures. 31 references. •

Eradication of Helicobacter Pylori with Pantoprazole and Two Antibiotics: A Comparison of Two Short-Term Regimens Source: Alimentary Pharmacology and Therapeutics. 14(9): 1151-1157. September 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: High rates of Helicobacter pylori (a bacterium that is a causative factor in peptic or stomach ulcer disease) eradication can be achieved by combining proton pump inhibitors with two antibiotics. However, in the search for an optimal therapy, a direct comparison of different regimens is necessary. This article reports on an open study of 331 patients with duodenal ulcer who were screened and randomly allocated to either pantoprazole 40 milligrams twice a day, clarithromycin 500 milligrams twice a day and metronidazole 500 milligrams twice a day (PCM regimen) or pantoprazole 40 milligrams twice a day, amoxycillin 1000 milligrams twice a day, and clarithromycin 500 milligrams twice a day (PAC regimen) for 7 days. Both combinations were followed by a 7 day therapy with pantoprazole 40 milligrames alone. Eradication of H. pylori was assessed by use of a 13C urea breath test 4 weeks after the intake of the last medication. Eradication rates were 90 percent in intention to treat patients from the PCM and the PAC group. H. pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96 percent) and in 119 out of 126 patients of the PAC group (94 percent). Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed. Adverse events were reported in 69 patients; none of the adverse events were related to the intake of pantoprazole. Four serious adverse events, none related to the trial medication, were observed. The authors conclude that both pantoprazole based short term triple therapies are highly effective and well tolerated treatment regimens in the eradication of H. pylori. 3 figures. 1 table. 18 references.

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Helicobacter Pylori Infection, Gastritis and Gastric Cancer: Helicobacter Pylori Infection Among Japanese Children Source: Journal of Gastroenterology and Hepatology. 15(12): 1382-1385. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: In Japan, there are few reports describing Helicobacter pylori infection among young children. This article reports on a study undertaken to identify risk factors associated with H. pylori in school aged children in Japan. Subjects were first grade students of three elementary schools (n = 310) and second grade students of a junior high school (n = 300). Personal information, such as students' medical history, parents' history, family size, siblings, and household pets, was collected using a questionnaire. Saliva samples and personal information were collected twice. Among the children, factors related to Helicobacter antibody in saliva included spending a longer period of time in a nursery school or kindergarten and a maternal history of stomach disease. Birth order, sleeping situation, and number of siblings were not factors that were significantly related to Helicobacter antibody in the saliva. Chewing food for the infant, family size, rooms in the household, sharing a bedroom during childhood, pets, a past

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history, and a paternal history were not related to positivity. The results indicate that transmission is person to person, mainly through close contact with other children and intrafamilial infection. H. pylori infection seems to occur frequently early in life, probably before 6 years of age. 2 tables. 29 references. •

Review Article. Helicobacter Pylori: Where Are We and Where Are We Going? Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 55-58. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: In this article, the author offers a personal view on what has been achieved in Helicobacter pylori research and what the expectations might be for further developments. The author stresses that knowledge about the organism is already extensive. Particularly intriguing are the differences in genetic makeup in the various geographical regions. However, detailed knowledge on how the organism spreads is still lacking. The clinical spectrum of the disease in man is largely known, but as H. pylori is disappearing worldwise, the relative frequency of H. pylori negative ulcer disease is increasing. To what extent H. pylori disappearance and eradication is responsible for the decreasing incidence of gastric cancer remains uncertain. Antimicrobial therapy is dominated by proton pump inhibitor (PPI) triple therapy as first line, with quadruple therapy as second-line therapy. The long term consequences of the rising resistance to the 'key' antimicrobials (clarithromycin, metronidazole) are so far unknown and speculative. The author notes that quadruple therapy appears less influenced by antimicrobial resistance compared with the other treatment modalities. 12 references.

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Future of Helicobacter Pylori Eradication: A Personal Perspective Source: Alimentary Pharmacology and Therapeutics. 11(Supplement 1): 109-115. April 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: In this article, the author presents a personal perspective on current issues in Helicobacter pylori eradication. The author notes that future changes in the use of H. pylori eradication therapy first will involve a decision-making process to determine which individuals require testing for the bacteria. Clearly, only persons who require therapy need to be diagnosed and, at present, the indications for therapy are constantly expanding. The author takes the view that everyone with H. pylori would be better off without the bacterium, but accepts that in many countries resources are inadequate to achieve this goal. Where antibiotic therapy for H. pylori fails because of a resistant organism, second treatment must include a different class of antibiotic. When a third therapy is contemplated, antibiotic sensitivity studies are usually necessary prior to therapy. In developing countries where reinfection with H. pylori is common, lesser goals than permanent cure might be appropriate. Thus, selected patients could have H. pylori suppressive therapy to prevent full expression of H. pylori-associated disease, or to prevent reinfection after an initial eradicative therapy. The author concludes that, after considering all these alternatives, a vaccination strategy, if safe and cost effective, is the ideal future therapy. 2 figures. 1 table. 30 references. (AA-M).

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Gastric Pathology Associated with Helicobacter Pylori Source: Gastroenterology Clinics of North America. 29(3): 705-751. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: In this article, the author reports on a study of approximately 8,000 gastric biopsy specimens, over a period of 20 years. The author has studied these cases in detail, with followup of 10 years in some cases. For much of this work, the author developed quantitative methods, particularly for the study of the antibacterial treatment of duodenal ulcers. The author discusses the range of changes seen in these biopsy specimens, the effect of treatment, and the relation of this work to that of other authors. The article discusses the history of Helicobacter infection and the histology of the normal stomach. The author examines the specific histological features related to Helicobacter pylori infection, including leukocyte infiltration of the epithelium, specific epithelial changes, and the morphology and distribution of the bacteria. Nonspecific changes, including atrophy, metaplasia, and stromal damage, are reported. Finally, the author describes special features: electron microscopy; changes after treatment; duodenal ulcer; other related conditions, including neoplasia; quantification of the histology; and the Sydney and Houston classifications. 27 figures. 7 tables. 23 references.

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In a World of Black and White, Helicobacter Pylori Is Gray Source: Annals of Internal Medicine. 130(8): 695-697. April 20, 1999. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: In this commentary article, the author reviews the past 15 years of treatment for Helicobacter pylori infections, focusing on the question, 'In whom is the elimination of H. pylori beneficial?' The author first summarizes the consensus about the role of H. pylori in gastric ulcer, the use of diagnostic tests to confirm its presence, and the natural history of the organism. The author then summarizes emerging issues, commenting that H. pylori strains are highly diverse and the type of strain with which an individual patient is colonized affects the risk for disease. The author also ponders the problem of increased rates of gastroesophageal reflux disease (GERD), Barrett's esophagus, and adenocarcinomas of the lower esophagus and gastric cardia, even as rates of peptic ulcer disease and noncardia gastric cancers have been decreasing. The role of H. pylori in these epidemiologic changes still needs much investigation. The author discusses terminology (e.g., colonization versus infection), clinical dilemmas, and the present challenges for physicians treating patients with H. pylori infections. The author concludes by recommending that physicians undertake a search for H. pylori only in patients with peptic ulcer disease and gastric MALT lymphomas. In such patients, the benefits of treatment seem to outweigh the risks and costs. However, before treating other patients, physicians should wait to learn what ongoing research will demonstrate. 20 references.

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Review Article: Helicobacter Pylori Vaccines-the Current Status Source: Alimentary Pharmacology and Therapeutics. 14(9): 1107-1118. September 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com.

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Summary: In this review article, the authors take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major etiologic factor (cause) of peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates, to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution, and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles, or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4 positive T cells are essential. Finally, the authors offer their viewpoint on whom should be immunized when a final vaccine becomes available. 63 references. •

Novel Therapies for Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 13(1): 35-41. January 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Increasing antibiotic resistance has begun to impair the ability to cure Helicobacter pylori (H. pylori) infection. This article reports on a study undertaken to evaluate orally administered novel therapies for the treatment of H. pylori infection. H. pylori infected volunteers received hyperimmune bovine colostral immune globulins, an oligosaccharide containing an H. pylori adhesion target, or recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. Results showed that none of the novel therapies appeared effective and no adverse events occurred. The authors conclude that, although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results. 3 figures. 1 table. 41 references. (AA-M).

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Pathogenesis of Helicobacter Pylori Infection Source: Current Opinion in Gastroenterology. 15(1): 66-71. January 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: Intensive investigation into Helicobacter pylori's interactions with the human host during the period of this review article (1998) has led to several important developments in the understanding of H. pylori pathogenesis. The authors note that direct evidence supports a central role for bacterial adhesion to host gastric epithelial (stomach lining) Lewis antigens. Adherence can result in activation of host signaling cascades, including tyrosine phosphorylation events. H. pylori induces an immune response that is skewed toward a T helper (Th) cell 1 phenotype, and an insufficient Th2 response is associated with the inability of the host to eradicate the organism. An area of active investigation has been the induction of epithelial apoptosis (sloughing off of the stomach lining), both in direct response to H. pylori and by T cell mediated pathways. Although the consensus is that the cagA gene product is not involved in pathogenesis,

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the presence of the cag pathogenicity island is associated with increased gastric inflammation and decreased epithelial repair. Interestingly, infection with cagA positive H. pylori appears to result in decreased prevalence of both gastroesophageal reflux disease and adenocarcinoma of the esophagus and cardia. However, this area of research is still controversial. 61 references (13 annotated). •

Helicobacter Pylori Eradication with Proton Pump Inhibitor-Based Triple Therapies and Re-Treatment with Ranitidine Bismuth Citrate-Based Triple Therapy Source: Alimentary Pharmacology and Therapeutics. 13(2): 163-168. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: It has been suggested that short term triple therapy with a proton pump inhibitor, plus clarithromycin and amoxycillin, be used as first choice in treating Helicobacter pylori infection, while eradication failure patients should be further treated with quadruple therapy. However, conflicting results have been reported using these treatment regimens in different countries. This article reports on a study in which a total of 278 patients with H. pylori infection were randomized to receive 1 week of triple therapy comprising clarithromycin 500 mg b.d., amoxycillin 1 g b.d., and either omeprazole 20 mg b.d. (OAC; 90 patients), or pantoprazole 40 mg b.d. (PAC; 95 patients), or lansoprazole 30 mg b.g. (LAC; 93 patients). H. pylori infection at entry, and eradication 4 to 6 weeks after therapy had ended, were assessed. When eradication did not occur, patients were given a 2 week treatment with ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s., and tinidazole 500 mg b.d. (RBTT regimen). Eradication in these patients was assessed by a further endoscopy 4 to 6 weeks after conclusion of treatment. Six patients were lost to the follow up. At the end of the first course of treatment, the overall H. pylori eradication rate was 78 percent at 'intention to treat' (ITT) and 79 percent at 'per protocol' (PP) analysis, without any statistically significant difference between regimens, although a trend for better results with the omeprazole combination was observed. H. pylori eradication was achieved in 82 to 86 percent of 38 patients retreated with the RBTT regimen. The authors conclude that this short term triple therapy is not a satisfactory treatment for H. pylori infection. The 2 week triple therapy used as retreatment in eradication failure patients yielded more promising results. 2 figures. 3 tables. 34 references. (AA-M).

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Alteration of Histological Gastritis After Cure of Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 16(11): 1923-1932. November 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: It is still disputed whether gastric (stomach) atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. If these condition improve, cure of the infection may reduce cancer risk. This article reports on a literature survey undertaken to clarify the histological changes after the cure of H. pylori infection. The authors reviewed 52 selected reports from 1,066 relevant articles. The extracted data were pooled according to histological parameters of gastritis based on the updated Sydney system. Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (more than 100 samples) and in two of five studies with

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a long follow up period (longer than 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Five of 28 studies described significant improvement of intestinal metaplasia. The authors conclude that activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. 5 tables. 65 references. •

Screening Dyspeptic Patients for Helicobacter Pylori Prior to Endoscopy: Laboratory or Near-Patient Testing? Source: European Journal of Gastroenterology and Hepatology. 10(10): 843-846. October 1998. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866. Summary: It is unclear whether near-patient whole blood diagnostic tests for Helicobacter pylori are comparable in accuracy to laboratory based enzyme-linked immunosorbent assay (ELISA) tests for screening dyspeptic patients before endoscopy. This article reports on a study undertaken to compare two ELISA and two whole-blood tests to determine whether near-patient H. pylori diagnostic tests are an acceptable alternative to laboratory based ELISA tests for screening dyspeptic patients before endoscopy. One hundred and seven consecutive patients with dyspepsia (median age 32 years; range 16 to 45 years) were evaluated with Helico-G ELISA, Hmcap ELISA, and Helisal whole blood tests. A further 111 dyspeptic patients (median age, 51 years; range, 16 to 96 years) were evaluated with the Immunocard whole blood test only. The gold standard for infection was based on histology and the rapid urease test (CLO). Compared with the Helico-G test, both near patient tests had a higher false negative rate and lower sensitivity and negative predictive value. The Immunocard had a higher specificity than the Helisal; otherwise, both near patient whole blood tests showed similar performance. At a sensitivity of 95 percent, the Hmcap ELISA was more specific than the Helico-G ELISA and had fewer false positives. The near-patient tests would wrongly classify up to 40 percent of H. pylori positive dyspeptic patients and exclude them from endoscopy, compared with 5 to 6 percent for ELISA. The authors conclude that near-patient whole blood H. pylori diagnostic tests are less accurate and thus not an acceptable alternative to laboratory based ELISA tests. 1 table. 16 references. (AA).

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Cost of Diagnosing Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 15(Supplement 1): 10-15. June 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Noninvasive testing and treatment for Helicobacter pylori have been recommended for dyspeptic patients in primary care and this article reviews a number of recent studies have demonstrated the cost effectiveness of this approach. As the prevalence of H. pylori infection declines, the positive and negative predictive values of individual tests will change. Cost effectiveness is important in determining the appropriate test in individual populations. Recent studies have shown that the stool antigen test and the urea breath test have high sensitivity and specificity in the detection

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of H. pylori infection before and after therapy. Cost effectiveness studies have shown that when the prevalence of H. pylori infection is low or intermediate, serological tests have relatively poor accuracy compared with the stool test or the urea breath test. In populations with low or intermediate prevalence (less than 60 percent) these tests should be preferred to ELISA serology or office based whole blood test or serology. This is particularly true when the prevalence of H. pylori infection is less than 30 percent as is seen in many developed countries. When the prevalence of H. pylori infection is high (greater than 60 percent), low cost antibody tests are cost effective. 42 references. •

Management Strategies for Helicobacter Pylori-Seropositive Patients with Dyspepsia: Clinical and Economic Consequences Source: Annals of Internal Medicine. 126(4): 280-291. February 15, 1997. Summary: Noninvasive testing for Helicobacter pylori is widely available and has been considered as an initial management strategy for uninvestigated dyspepsia. However, data to guide clinicians in the management of patients with dyspepsia who are seropositive for H. pylori are lacking. This article reports on a study to examine the economic, clinical, and policy implications of alternative initial management strategies for patients with uninvestigated dyspepsia who are seropositive for H. pylori. Cost estimates were obtained from the Medicare reimbursement schedule and a health maintenance organization pharmacy; probability estimates were derived from the medical literature. Initial endoscopy costs an average of $1,276 per patient, whereas initial anti-H. pylori therapy costs $820 per patient; the average saving is $456 per patient treated. The financial effect of a 252 percent increase in the use of antibiotics for initial H. pylori therapy is more than offset by reducing the endoscopy workload by 53 percent. Endoscopy-related costs must be reduced by 96 percent before the two strategies become equally cost effective. In patients with nonulcer dyspepsia, the financial benefits of initial anti-H. pylori therapy are not substantially affected by varying the rates of H. pylori eradication, the complications of antibiotics, or the response of symptoms to cure of H. pylori infection. The authors conclude that, unless physicians are concerned about resistance to antimicrobial agents or the lack of proven benefit of anti-H. pylori therapy in nonulcer dyspepsia, the strategy outlined in this analysis can be used as a basis for management and policy decisions about H. pylori seropositive patients with dyspepsia. The article is accompanied by a related editorial. 4 figures. 6 tables. 86 references. (AA-M).

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Effects of Pumaprazole (BY841), A Novel Reversible Proton Pump Antagonist, and of Omeprazole, on Intragastric Acidity Before and After Cure of Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 13(1): 27-34. January 1999. Contact: Available from Blackwell Science Ltd. Journal Subscriptions, P.O. Box 88, Oxford OX2 ONE, UK. 44(0) 1865 206180 or 206038. Fax: 44(0) 1865-206219. E-mail: [email protected]. Summary: Omeprazole (a proton pump inhibitor) produces a higher intragastric pH in the presence of Helicobacter pylori infection before cure than after cure. This article reports on a study undertaken to investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell. In a randomized, crossover, double blind study, 24 hour intragastric (in the stomach) pH was measured in 13 H. pylori positive subjects before and after a 1 week course of

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omeprazole or of pumaprazole. The studies were repeated after the infection was cured. In the absence of drug administration, the median 24 hour pH values before cure did not differ from those after cure. However, the 24 hour pH values were higher before cure of the infection than after during both pumaprazole and omeprazole. Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24 hour period. The median decrease in acid inhibition after cure of the infection during pumaprazole was no different from that during omeprazole. H. pylori infection similarly augments the pH increasing effect of both drugs. This authors stress that this effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment. 4 figures. 2 tables. 28 references. •

Treatment of Helicobacter Pylori Source: Current Opinion in Gastroenterology. 15(1): 72-78. January 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: Overwhelming evidence implicates Helicobacter pylori as a significant causative factor in many gastroduodenal diseases. This article reviews the advances made in the past year in the treatment of H. pylori. Effective multidrug antimicrobial regimens are available to cure the infection, so investigative efforts are focusing on cost effectiveness and treatment outcome in various populations. Potential associations between H. pylori and nongastric disorders are also being examined. Recognition that infection is largely acquired during childhood has emphasized the need to study pediatric issues. Posttreatment studies confirm the importance of the bacterium in pathogenesis and relapse of peptic ulcer disease (PUD). Antimicrobial resistance has a negative impact on cure of the infection and healing of gastroduodenal lesions. Methodology to evaluate H. pylori antimicrobial susceptibility has been standardized by the National Committee for Clinical Laboratory Standards, and minimum inhibitory concentration breakpoints to standardize resistance assays are being established. Surveillance of H. pylori antimicrobial resistance is underway in a Centers for Disease Control and Prevention (CDC) multisite project. The authors conclude that multidrug antimicrobial regimens are most effective in curing H. pylori infection. Triple therapy regimens with proton pump inhibitors (PPI) appear to be more effective, better tolerated, simpler, and associated with better compliance than other regimens. 39 references (7 annotated).

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Helicobacter Pylori and Risk of Ulcer Bleeding Among Users of Nonsteroidal AntiInflammatory Drugs: A Case-Control Study Source: Gastroenterology. 116(6): 1305-1309. June 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Peptic ulcer complications related to use of nonsteroidal antiinflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. The role of Helicobacter pylori infection in causing or contributing to this gastrointestinal toxicity of NSAIDs is still unresolved. This article reports on a case control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid, aspirin), admitted to the hospital because of bleeding peptic ulcer. The controls were 136 NSAID users who did not have gastrointestinal complications. H. pylori was diagnosed by either increased levels of serum immunoglobulin G or by 13C urea breath test. Fifty-eight (44 percent) case subjects had a bleeding gastric ulcer, 54 (41 percent) had a bleeding duodenal ulcer,

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12 (9 percent) had both gastric and duodenal ulcers, and 8 (6 percent) had hemorrhagic gastritis. H. pylori was present in 75 (57 percent) cases compared with 59 (43 percent) controls. The adjusted odds ratio of bleeding peptic ulcer among NSAID users associated with H. pylori infection was 1.81. H. pylori accounted for approximately 24 percent of bleeding peptic ulcers among elderly NSAID users. The authors conclude that NSAID users infected with H. pylori have an almost twofold increased risk of bleeding peptic ulcer compared with NSAID users without H. pylori infection. 2 tables. 23 references. •

Scope and Consequences of Peptic Ulcer Disease: How Important Is Asymptomatic Helicobacter Pylori Infection? Source: Postgraduate Medicine. 105(3): 100-102, 105-108, 110. March 1999. Summary: Peptic ulcer disease (PUD) is a worldwide problem, affecting 1 in 10 people. Similarly, Helicobacter pylori, the now undisputed culprit in most cases of PUD, is found virtually everywhere on the planet. Although the organism causes problems in only a minority of those who carry it, it is linked to a number of serious consequences. In this article, a panel of experts discusses the scope, risks, and relationships of H. pylori and peptic disease, cancer, and other disorders. Transmission is believed to be primarily person to person. The pathogen invariably damages the gastric mucosa, resulting in both structural and functional abnormalities. H. pylori causes histologic gastritis and is critical in the pathogenesis of the gastritis associated diseases: gastric ulcer, duodenal ulcer, gastric adenocarcinoma, and primary gastric lymphoma. Elimination of the infection results in healing of gastritis and cure of PUD. 2 tables. 28 references. (AA-M).

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Risk of Ulcer Bleeding in Patients Infected with Helicobacter Pylori Taking NonSteroidal Anti-Inflammatory Drugs (commentary) Source: Gut. 46(3): 310-311. March 2000. Contact: Available from BMJ Publishing Group. P.O. Box 590A, Kennebunkport, ME 04046. (800) 236-6265. Summary: This article reports on a study to determine whether Helicobacter pylori is an independent risk factor for bleeding peptic ulcer in users of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. The prospective matched case control study included 132 patients with a bleeding peptic ulcer (n = 124) or hemorrhagic gastritis (n = 8) at endoscopy who had taken an NSAID in the previous week, and 136 controls who had taken NSAIDs without gastrointestinal complications. The controls were recruited from rheumatology and geriatric outpatient clinics. H. pylori was present in 57 percent of cases and 43 percent of controls. The adjusted odds ratio of bleeding from a peptic ulcer owing to H. pylori infection in NSAID users was 1.81 and was similar in aspirin and nonaspirin NSAID users. Peptic ulcer bleeding was also statistically significantly associated with a history of previous ulcer bleeding, dyspepsia within the previous 3 months, and drinking alcohol, but not with smoking. The authors contend that about 16 percent of bleeding peptic ulcers in NSAID users could be attributed to H. pylori infection. NSAID users infected with H. pylori have an almost doubled risk of bleeding peptic ulcer compared with uninfected NSAID users. 12 references.

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Accuracy of the Stool Antigen Test in the Diagnosis of Helicobacter Pylori Infection Before Treatment and in Patients on Omeprazole Therapy Source: Alimentary Pharmacology and Therapeutics. 15(1): 73-79. January 2001.

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Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article reports on a study undertaken to evaluate the Helicobacter pylori stool antigen (HpSA) test in the assessment of H. pylori infection and the effect of omeprazole treatment on its accuracy. In the first study, 140 patients with dyspepsia (heartburn, indigestion) were enrolled and defined as H. pylori positive if histology and rapid urease test, or culture alone, were positive. HpSA was performed on all patients and 13C urea breath test (UBT) on 87 patients. In the second study, 75 patients testing positive using both UBT and HpSA were given omeprazole 20 mg for 2 weeks (Group A) or omeprazole 40 mg for 2 weeks (Group B), or omeprazole, amoxicillin, clarithromycin OAC for 1 week (Group C). Results showed that 80 of 140 patients were H. pylori positive. The sensitivity and specificity of HpSA were 93.8 and 90 percent, similar to UBT (93.9 and 92.1 percent, respectively). Omeprazole significantly reduced both HpSA and UBT values, resulting in a decreased accuracy. Of 25 patients receiving 20 mg of omeprazole, HpSA gave 5 and 6 false negatives after 7 and 14 days treatment respectively, while UBT gave 4 and 7 false negatives after 7 and 14 days treatment. Of the 25 patients receiving 40 mg omeprazole, HpSA gave 7 and 9 false negatives after 7 and 14 days of treatment, while UBT gave 8 and 9 false negatives after 7 and 14 days of treatment. Two weeks after stopping omeprazole treatment, the HpSA and UBT were positive in all cases. The authors conclude that the H. pylori stool antigen test is valuable in the assessment of H. pylori infection. Short term omeprazole treatment decreases the accuracy of both HpSA and UBT in a similar manner. 3 figures. 1 table. 33 references. •

Helicobacter Pylori Gastritis and Gastric Physiology Source: Gastroenterology Clinics of North America. 29(3): 687-703. September 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32821-9816. (800) 654-2452. Summary: This article reviews Helicobacter pylori gastritis and gastric physiology. Helicobacter pylori gastritis (stomach inflammation) can alter stomach physiology, leading to increased or decreased acid secretion, depending on the pattern of gastritis present. These changes in physiology are related to the disease outcome, with increased acid secretion leading to duodenal ulcer disease and reduced acid secretion being a risk factor for gastric (stomach) cancer. Gastric acid secretion also affects the pattern of gastritis induced by the infection, with low acid secretion leading a pangastritis and possibly atrophy. This two way interaction between H. pylori gastritis and gastric acid secretion is important in understanding the role of H. pylori infection in the response to proton pump inhibitor therapy. This interaction explains the more profound control of gastric acid secretion in H. pylori positive patients and why rebound acid hypersecretion is confined to H. pylori negative subjects. 6 figures. 60 references.

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Endoscopic Methods for the Diagnosis of Helicobacter Pylori Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 3-9. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected].

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Summary: This article reviews endoscopic methods for the diagnosis of Helicobacter pylori. The authors note that at the time of endoscopy, certain findings (gastroduodenal ulceration and or antral nodularity) may be highly suggestive of H. pylori infection. Endoscopic acquisition of gastric biopsies, however, leads to a definitive diagnosis of infection on the basis of both direct and indirect tests. Direct tests include culture and histological detection (considered the gold standard). There are a variety of stains available for the detection of H. pylori; their choice is influenced by local expertise and the clinical situation. If at least three biopsies are obtained from nonadjacent gastric sites, incorrect assessment of H. pylori status should be rare. Indirect methods utilize the detection of urease. The three biopsy rapid urease tests commercially available in the United States have similar performance characteristics, except that two are gel tests requiring up to 24 hours to read, while one is a strip test that is read up to 1 hour. Specificity is excellent for these tests, while sensitivity is more variable. Rapid urease tests are the endoscopic tests of choice for initial evaluation due to their low cost. The authors note that diagnostic methods for H. pylori are of special interest because therapy for the infection is not 100 percent effective. Therefore, assessment of cure after treatment is important, especially in patients with either complicated ulcers or gastric MALT lymphomas. 1 table. 28 references. (AA-M). •

Role of Helicobacter Pylori in Extradigestive Diseases Source: Current Opinion in Gastroenterology. 15(Supplement 1): S29-S33. 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: This article reviews recent studies on the association between Helicobacter pylori infection and various extragastroduodenal (outside the stomach and duodenum) diseases, including cardiovascular, immunological, and miscellaneous other pathologies. The correlation between H. pylori and cardiovascular (heart) diseases appears to remain contentious, while association with some autoimmune diseases is supported by growing evidence. Recent studies have correlated H. pylori infection with functional vascular disorders, such as primary Raynaud's phenomenon and migraine. The mechanisms behind this phenomenon remain unknown, but some role for cytokines, prostaglandins, leukotrienes, and other vasoactive substances that are released as a consequence of H. pylori infection has been suggested. Finally, various Helicobacter species have been detected in the liver and bile; this important finding could lead to a revision of diagnostic and therapeutic approaches to various idiopathic diseases (those without a known cause) of the hepato-biliary tract. The author concludes that increasing evidence seems to support the existence of at least some extragastric manifestations of H. pylori infection. 46 references (18 annotated).

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Diagnosis of Helicobacter Pylori Source: Practical Gastroenterology. 25(4): 28, 30, 32, 34-37, 41. April 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This article reviews the diagnosis of Helicobacter pylori infection, focusing on patient selection issues (which patients should be tested for this infection). There is a clear link between Helicobacter pylori infection and the pathogenesis (development) of peptic ulcer disease (PUD). Cure of this infection is the most cost effective means of managing patients with PUD. A consensus conference statement from the National Institutes of Health recommended that all patients with PUD and those on long term

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medical therapy for a history of PUD should be tested for H. pylori. The incidence of H. pylori infection in patients with gastric adenocarcinoma (stomach cancer), and non Hodgkins lymphoma is significantly higher than in controls. In addition, a recent medical position statement by the American Gastroenterological Association recommended that patients with dyspepsia (indigestion, heartburn) under the age of 45 to 50 years with no 'alarm features' undergo a test and treat strategy for H. pylori. In this strategy, patients undergo a non endoscopic test for H. pylori and those with a positive test receive antimicrobial therapy. The test and treat strategy may reduce the utilization of upper endoscopy (EGD) and costs associated with the care of patients with dyspepsia. The author reviews the nonendoscopic and endoscopic tests that can be used for H. pylori detection, including those used to prove cure of H. pylori infection after treatment. The author concludes that it is important to consider overall costs associated with testing (including costs for inappropriate therapy and its consequences or lack thereof) rather than only the acquisition costs associated with a specific test. 1 figure. 2 tables. 48 references. •

Extradigestive Manifestations of Helicobacter Pylori Infection: Fact and Fiction Source: Digestive Diseases and Sciences. 44(2): 229-236. February 1999. Contact: Available from Plenum Publishing Corporation. 233 Spring Street, New York, NY 10013. (212) 620-8468. Fax (212) 807-1047. Summary: This article reviews the extradigestive manifestations of Helicobacter pylori (H. pylori) infection. H. pylori infection is the main etiological factor for gastritis and peptic ulcer and has recently been found to have a potential role in several extraintestinal pathologies. The postulated role of H. pylori in the pathogenesis of extraintestinal manifestations is based on the facts that local inflammation has systemic effects, H. pylori gastric infection is a chronic process lasting for decades, and persistent infection induced a chronic inflammatory and immune response capable of inducing lesions both locally and remote to the primary site of infection. The authors review the available literature about extradigestive manifestations of H. pylori infection. Topics include vascular diseases and H. pylori infection, including coronary heart disease, primary Raynaud's phenomenon, functional vascular disorders, and primary headaches; autoimmune diseases, including Sjogren's syndrome, Schonlein-Henoch purpura, and autoimmune thyroiditis; skin diseases; and other diseases associated with H. pylori infection. 1 figure. 1 table. 70 references.

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Review Article: Non-Steroidal Anti-Inflammatory Drugs and Helicobacter Pylori Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 43-47. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article reviews the impact of nonsteroidal antiinflammatory drugs (NSAIDs) and Helicobacter pylori, both well recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prostaglandin metabolism. Clinical trials on the interrelationship between H. pylori, NSAIDs, and gastroduodenal mucosal injury have yielded conflicting results. The authors note that no consensus has been reached on what recommendations should be implemented with regard to H. pylori eradication in patients on long term NSAID therapy. Currently, the presence of H. pylori is identified

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at endoscopy and eradication of the bacterial infection is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients on NSAID therapy and at risk of gastrointestinal hemorrhage, acid suppression therapy should be prescribed. 23 references. •

Lack of Effect of Treatment for Helicobacter Pylori on Symptoms of Nonulcer Dyspepsia Source: Archives of Internal Medicine. 159(19): 2283-2288. October 25, 1999. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10946, Chicago, IL 60610-0946. (800) 262-2350. Fax (312) 464-5831. E-mail: [email protected]. Summary: Prior studies have yielded conflicting results on whether or not Helicobacter pylori causes nonulcer dyspepsia. This article reports on a study undertaken to determine whether H. pylori infection causes nonulcer dyspepsia. The study enrolled 100 consecutive patients with nonulcer dyspepsia into a randomized, doubleblind, placebo controlled trial. Patients with peptic ulcer disease, esophagitis, hepatobiliary disease, irritable bowel disease (IBS), or predominately reflux related symptoms were excluded by history and upper endoscopy. H. pylori infection was determined by biopsy and histologic examination. Enrolled patients were randomized to a 14 day regimen of omeprazole (20 mg twice daily) and clarithromycin (500 mg three times daily) or placebo. Dyspeptic symptoms were assessed by use of a visual analog scale at baseline and at 1, 3, 6, and 12 months after treatment. Followup upper endoscopy with biopsy was performed 4 weeks after treatment. Compliance was measured by tablet counts. At 1 year, the change in dyspeptic symptoms was negative 24.0 in the omeprazole and clarithromycin group and negative 24.2 in the placebo group. Furthermore, patients with persistent H. pylori infection demonstrated a greater, but not significant, improvement in symptoms than those with successful eradication. The authors conclude that patients with nonulcer dyspepsia should not routinely be treated for H. pylori, since it is not a cause of this condition in most patients. 3 figures. 2 tables. 34 references.

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Eradication of Helicobacter Pylori Increases Gastric Acidity in Patients with Atrophic Gastritis of the Corpus: Evaluation of 24-h pH Monitoring Source: Alimentary Pharmacology and Therapeutics. 13(2): 155-162. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion that decreases to normal levels in patients with duodenal ulcer disease. This article reports on a study undertaken to evaluate the effect of eradicating H. pylori in a 24 hour study of gastric acidity in patients with atrophic gastritis of the corpus. Intragastric acidity was measured by continuous 24 hour pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pylori positive patients (10 men, 4 women; mean age 57 years)with histologically proven atrophic gastritis of the corpus before and 1 year after anti H. pylori therapy. H. pylori was absent in 13 of 14 patients 1 year after treatment. Both gastritis and atrophy scores were significantly lower after eradication therapy. The 24 hour medical pH and the percentage of 24 hour pH readings above 4.0 units were significantly decreased after

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eradication therapy. The authors conclude that improving the histology of the gastric antrum and corpus may lead to the normalization of gastric acidity. 3 figures. 1 table. 45 references. (AA-M). •

Helicobacter Pylori Antibiotic Resistance: Trends Over Time Source: Canadian Journal of Gastroenterology. 14(10): 895-899. November 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: Resistance to antibiotics can be a major problem in the treatment of bacterial infections. As the use of antibiotics increases, bacterial resistance to these agents is rising and in many cases is responsible for the failure of treatment regimens. This review article considers the trends in H. pylori antibiotic resistance over time. Although the treatment of H. pylori infection requires the use of more than one antibiotic to obtain adequate eradication rates, the efficacy of the currently used antibiotic combinations has been shown to be decreased by resistance to one of the antibiotics. The use of antibiotics in regimens for the treatment of H. pylori is increasing in many countries, including Canada. This increase is both in the use of these antibiotics alone for the treatment of nongastrointestinal infections and in their use in association with proton pump inhibitors for the treatment of H. pylori infection. In several European and Asian countries, where resistance to antibiotics is being monitored, it has been demonstrated that H. pylori resistance to metronidazole and to clarithromycin increased throughout the 1990s. Thus far, the data available in Canada do not show increased resistance to either of these antibiotics. As for other antibiotics used in the treatment of H. pylori infection, such as tetracycline and amoxicillin, the rate of resistance to these agents is still very low and does not constitute a significant problem. However, because the efficacy of the regimens used in the treatment of H. pylori infection is compromised by resistance to the antibiotics used, it is important that H. pylori resistance rates in Canada and throughout the world continue to be monitored. 6 figures. 2 tables. 32 references.

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One-week Triple vs. Quadruple Therapy for Helicobacter Pylori Infection: A Randomized Trial Source: Alimentary Pharmacology and Therapeutics. 16(7):1261-1267. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Seven day triple therapy (omeprazole, clarithromycin, and amoxicillin) has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole, and bismuth may be an alternative to triple therapy. This article reports on a study undertaken to compare triple versus quadruple therapy for H. pylori eradication. The study included 339 patients with peptic ulcer and H. pylori infection. No significant differences between the triple versus quadruple therapy groups were found in the cure rates, compliance, or side effects. The authors conclude that one week triple and quadruple therapy show similar results when used as first line eradication treatment. 2 figures. 1 table. 33 references.

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Helicobacter Pylori Infection Source: New England Journal of Medicine. 347(15): 1175-1186. October 10,2002.

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Summary: Since the first culture of Helicobacter pylori 20 years ago, the diagnosis and treatment of upper gastroduodenal disease have changed dramatically. This review surveys scientific knowledge concerning H. pylori and focuses on the many aspects of this infection that are relevant to the clinician. The authors discuss epidemiology and transmission, pathogenesis, host responses to H. pylori, clinical outcomes of infection, diagnostic tests, treatment of H. pylori infection, first line therapies, proton pump inhibitor (PPI) based triple therapies, ranitidine bismuth citrate based therapies, bismuth based triple therapies, second-line therapies, and indications for therapy. Peptic ulcer disease is now approached as an infectious disease, in which elimination of the causative agent cures the condition. The role of H. pylori infection in gastric cancers is increasingly recognized, and its role in other diseases of the upper gastrointestinal tract is being evaluated. Effective antimicrobial therapy is available, although there is still no ideal treatment, and indications for therapy continue to evolve. 3 figures. 2 tables. 107 references. •

Helicobacter Pylori-Positive Functional Dyspepsia in Elderly Patients: Comparison of Two Treatments Source: Digestive Diseases and Sciences. 44(5): 863-867. May 1999. Summary: The association between Helicobacter pylori and functional dyspepsia is not well defined. The role of H. pylori in dyspeptic symptoms is still controversial. This article reports on a study undertaken to confirm the efficacy of H. pylori eradication by two different commonly used treatment regimens, as well as to examine the improvement of the dyspeptic symptoms by eradicating H. pylori. In the age group over 60 years, the authors treated 126 patients with bismuth plus metronidazole and amoxicillin (group A, 67 patients) versus omeprazole plus amoxicillin (group B, 59 patients). Two months after the end of therapy the authors observed an eradication rate of 66.1 percent in group A versus 64.3 percent in group B. All treated patients showed improvement in symptomatology. Although there was no significant difference between patients in whom H. pylori was or was not eradicated within the respective groups, when examining all H. pylori positive patients versus H. pylori negative posttreatment patients, there was a significant reduction in all four symptoms of functional dyspepsia measured. In conclusion, the authors suggest that patients treated with H. pylori eradicating therapeutic regimens have an improvement in functional dyspepsia symptoms. The authors prefer the dual therapy as compared to the triple therapy. The authors also note that eradicating treatment to eradicate H. pylori in the elderly patients with H. pylori related functional dyspepsia will reduce health care costs by reducing the number of subsequent visits. 5 tables. 15 references. (AA-M).

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Practical Advice On Eradicating Helicobacter Pylori Infection Source: Postgraduate Medicine. 105(3): 137-140, 145-148. March 1999. Summary: The days of putting patients with peptic ulcers on a diet of bland food and antacids are past. Today, curing ulcers is simply a matter of eradicating Helicobacter pylori infection. The authors of this article, the third in a series on peptic ulcer disease (PUD), question whether it is really that simple. The authors summarize combination regimens that have been found to be most effective against the organism and discuss what to do when such treatment fails. They also discuss issues to consider in preventing drug resistance and provide tips on improving patient compliance, which is vital to successful treatment. The important factors in selecting therapy are efficacy of eradication, prevention of resistance, avoidance or minimization of adverse effects, patient compliance, and cost. The most effective regimens include a bismuth preparation

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or antisecretory drug (proton pump inhibitor or H2 receptor antagonist) plus two antibiotics administered for 14 days. Dual drug therapies are not recommended. Triple drug regimens are more likely to eradicate H. pylori and less likely to generate resistant strains among surviving organisms. In general, cure of the infection should be confirmed 4 weeks after completion of the treatment. Antibiotic resistance is an important consideration in choosing therapy, and patients should be taught the importance of compliance. When treatment fails, antibiotic combinations should not be repeated. Considerations for anti H. pylori treatment in a managed care environment mirror those for good medical practice in general, with special attention to stringent cost control or outcomes driven measures. The authors include a patient care algorithm for treatment decisions in patients with suspected PUD associated with H. pylori infection. 1 figure. 1 table. 22 references. (AA-M). •

Cure of Helicobacter Pylori Infection in Atrophic Body Gastritis Patients Does Not Improve Mucosal Atrophy But Reduces Hypergastrinemia and Its Related Effects on Body ECL-Cell Hyperplasia Source: Alimentary Pharmacology and Therapeutics. 14(5): 625-634. May 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The effects of Helicobacter pylori eradication on atrophic body gastritis are controversial. This article reports on a study undertaken to investigate the effect of triple therapy on atrophic body gastritis in H. pylori positive patients and its effect on morphofunctional gastric parameters. Consecutive patients (n = 35) with atrophic body gastritis with histological or serological evidence of H. pylori infection were treated. Before and 6 and 12 months after H. pylori eradication the patients were evaluated for fasting gastrinemia and pepsinogen I, basal and peak acid output, and detailed histological assessment including the ECL cell proliferative patterns. Six months after treatment, 25 out of 32 patients were cured (78 percent). Cure of infection was associated with improvement in both basal and stimulated acid secretion, as well as with reduction in hypergastrinemia. In contrast, the eradication had no effect on body corporal atrophy and intestinal metaplasia, or pepsinogen I levels. These results were confirmed at 12 months after eradication. A statistical inverse correlation was obtained between the corporal chronic infiltrate score and peak acid output values. A total of 53 percent of atrophic body gastritis patients showed a regression in severity of body ECL cell hyperplastic change. The authors conclude that cure of H. pylori infection in patients with atrophic gastritis reverses some adverse effects on gastric function and ECL cell hyperplasia. 3 figures. 2 tables. 38 references.

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Eradicating Helicobacter Pylori Infection Source: Patient Care. 35(7): 91-92, 94, 97-100. April 15, 2001. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: The eradication of Helicobacter pylori infection is now recognized as an integral component in the successful management of patients with peptic ulcer disease (PUD). The diagnosis of an active H. pylori infection can be made using the noninvasive urea breath test, serology, stool antigen test, or one of several biopsy based tests. H. pylori eradication is best accomplished with triple therapy consisting of a proton pump inhibitor (PPI) plus clarithromycin plus either amoxicillin or metronidazole given twice

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daily for 10 to 14 days. This regimen provides a cost effective means for reducing ulcer recurrence and complications. This article reviews the patient indications for H. pylori eradication and discusses general patient care management. The author notes that testing should only be conducted if eradication therapy will be used. Physicians should consider testing patients with recurrent dyspeptic symptoms, including epigastric pain (heartburn), abdominal discomfort, and nausea. The test should be matched to patient characteristics. Gastric mucosal (stomach lining) biopsy offers high sensitivity and specificity but is invasive. Serologic (blood) tests are the noninvasive approaches most commonly used. Antibiotic resistance to clarithromycin may slow treatment effectiveness. Confirmation of the successful eradication of H. pylori is not necessary in asymptomatic patients with uncomplicated peptic ulcer. Long term antisecretory therapy may be needed in patients who fail to respond to H. pylori eradication therapy and in those in whom antibiotic therapy may be too complicated or otherwise contraindicated. 2 tables. 25 references. •

Third Line Treatment for Helicobacter Pylori: A Prospective, Culture-Guided Study in Peptic Ulcer Patients Source: Alimentary Pharmacology and Therapeutics. 14(10): 1335-1338. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The first line treatment of Helicobacter pylori bacterial infection cures the infection in the majority of patients. However, failures are common and 5 to 25 percent of patients remain infected in spite of using current recommended regimens. Even after two courses of treatment, 2 to 5 percent of patients remain infected. This article reports on a prospective study undertaken to investigate the effectiveness of third line treatment of H. pylori infection in patients with ulcers. Two week quadruple, culture guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studies by E test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks. Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate of 36 percent (five patients out of 14). If amoxycillin was used in place of the clarithromycin, the rate was 67 percent (eight patients out of 12). The difference was not significant. No clinical factor was found to be associated with failure to eradicate. The authors conclude that third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation. 2 tables. 15 references.

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GERD and H. Pylori: Does It Matter? Source: Practical Gastroenterology. 25(7): 26, 31-32, 34, 36-37. July 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: The incidence of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma (cancer of the esophagus) have increased in recent years while the incidence of peptic ulcer disease (PUD) and distal gastric (stomach) cancer have declined. Given the simultaneous decline in Helicobacter pylori infection, it is tempting to propose a relationship between H. pylori infection and these opposing time trends. This review article puts into perspective the current understanding of the complex,

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incompletely understood relationship between H. pylori infection and GERD. While H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from developing GERD and its complications. The most likely mechanism whereby H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. 4 figures. 20 references. •

Non-Helicobacter Pylori, Non-NSAID Peptic Ulcer Disease Source: Practical Gastroenterology. 25(9): 15, 18,20, 22. September 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: The majority of patients with peptic ulcers are infected with Helicobacter pylori bacteria but the organism may not always be responsible for the ulcer. Most patients have more than one risk factor for ulceration that then makes it difficult to establish the exact cause for the peptic ulcer. This article summarizes the current thinking in the etiology (cause) of peptic ulcer disease (PUD) and updates the reader on the prevalence and management of H. pylori, NSAID (nonsteroidal antiinflammatory drug) negative ulcer disease. Ulcer studies in the United States have found that approximately 20 percent of patients with duodenal ulceration have ulcer recurrence despite successful eradication of H. pylori. The phenomenon of non-H. pylori, nonNSAID mediate ulcer disease is also being increasingly recognized as defining a distinct subgroup of ulcer patients who have true idiopathic (with unknown cause) ulcer disease. The etiology for ulceration in these patients and their management is not well understood. The authors concludes that patients with an idiopathic duodenal ulcer have gastric (stomach) acid hypersecretion and are likely to have a more complicated course than their H. pylori-positive counterparts. 1 table. 18 references.

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Usefulness of Helicobacter Pylori Stool Antigen Test to Monitor Response to Eradication Treatment in Children Source: Alimentary Pharmacology and Therapeutics. 15(2): 203-206. February 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The monitoring of the results of eradication treatment is a crucial step for patients with Helicobacter pylori gastritis. A noninvasive test for H. pylori antigens in stools (HpSA) was recently validated for children. This article reports on a study undertaken to evaluate the accuracy of HpSA in monitoring eradication treatment in children. In 60 children, H. pylori gastritis was diagnosed by endoscopy and the 13C urea breath test. The children were treated and returned for a followup 13C urea breath test 6 weeks after the end of treatment. Children were considered cured when the 13C urea breath test was negative. Stool were collected at baseline and at 2 and 6 weeks. Stool antigens were measured by HpSA. According to 13C urea breath test, 6 weeks after the end of treatment, 49 children were cured and 11 were still H. pylori positive. The sensitivity and specificity of HpSA on stools collected 2 weeks after therapy were 100 percent. At 6 weeks, specificity was 93.9 percent and sensitivity 100 percent. Results by visual reading were concordant with the plate reader in all but two cases at baseline.

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The authors conclude that HpSA is accurate for monitoring treatment in children as early as 2 weeks after therapy, when information is most useful and unachievable with other tests. In addition, the HpSA is more cost effective than the 13C urea breath test and it is not available everywhere. Results of the HpSA by visual reading are accurate, and this can make the test cheaper and more practical. 1 figure. 1 table. 8 references. •

Helicobacter Pylori-Positive Duodenal Ulcer: Three-Day Antibiotic Eradication Regimen Source: Alimentary Pharmacology and Therapeutics. 14(10): 1329-1334. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The most widely used treatments for ulcer healing and Helicobacter pylori eradication consists of a 1 to 2 week regimen of a proton pump inhibitor (PPI) plus two or three antimicrobials. This article reports on a study undertaken to evaluate the efficacy, safety, cost, and tolerance of a three day regimen with three antibiotics versus a 10 day treatment with a PPI inhibitor or versus a ranitidine bismuth citrate triple therapy. The study included 221 patients with endoscopically proven H. pylori positive duodenal ulcers. Recruited patients were assigned to one of four regimens: OAC (n = 55 patients) consisting of omeprazole, amoxycillin, clarithromycin; OACM (n = 56 patients), consisting of omeprazole, amoxycillin, clarithromycin, and metronidazole; RAC (n = 54 patients), consisting of ranitidine bismuth citrate, amoxycillin, and clarithromycin; or RACM (n = 56 patients) consisting of ranitidine bismuth citrate, amoxycillin, clarithromycin, and metronidazole. Fisher's exact test was used to compare data regarding healing and eradication in the four groups. The intention to treat eradication and ulcer healing rates for the RACM regimen were 95 percent and 98 percent, respectively. Statistically significant differences were observed, relating to the eradication and healing of ulcers, between RACM and either the RAC or OAC regimens. The authors conclude that the three day antibiotic therapy with amoxycillin, clarithromycin, and metronidazole, in addition to ranitidine bismuth citrate, is a very effective anti H. pylori regimen. 1 figure. 3 tables. 26 references.

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Failure of a 1-Day High-Dose Quadruple Therapy for Cure of Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 13(2): 173-177. February 1999. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The optimal duration of treatment for eradication of Helicobacter pylori has still to be defined. A 1 day, high dose, quadruple therapy with a combination of amoxycillin (or tetracycline), metronidazole, a bismuth salt, and a proton pump inhibitor has led to eradication rates of 57 to 77 percent. This article reports on a study in which the authors hypothesized that by using clarithromycin in place of metronidazole and by increasing the dose of proton pump inhibitor, the efficacy of a this therapy could be improved. The authors focused on this aspect of the therapy because of the high frequency of metronidazole resistant strains of H. pylori in Europe. The authors originally intended to include 100 patients. The first planned interim analysis performed after follow up was completed for 30 patients and revealed H. pylori eradication rates of 80 percent (12 out of 15 patients) in the 7 day triple therapy group (amoxycillin 1000 mg

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b.d., clarithromycin 500 mg b.d., and lansoprazole 30 mg b.d.) and 20 percent (3 out of 15 patients) in the 1 day quadruple therapy group (amoxycillin 2000 mg q.d.s., clarithromycin 500 mg q.d.s., lansoprazole 30 mg t.d.s., and bismuth subcitrate 240 mg q.d.s. for 1 day); the difference was highly significant (P = 0.003). Because the efficacy of the 1 day treatment was so low, the study was stopped for ethical reasons. Eleven patients who failed with the 1 day treatment were given the 7 day triple therapy: the eradication rate was then 91 percent (10 out of 11 patients). The authors conclude that 1 day, high dose quadruple therapy with amoxycillin, clarithromycin, lansoprazole, and bismuth subcitrate is dramatically less effective than the classic 7 day triple therapy with the same antibiotics. 3 tables. 32 references. (AA-M). •

Furazolidone-Based Triple 'Rescue Therapy' vs. Quadruple 'Rescue Therapy' for the Eradication of Helicobacter Pylori Resistant to Metronidazole Source: Alimentary Pharmacology and Therapeutics. 16(7):1277-1282. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The optimal treatment of patients with Helicobacter pylori who are resistant to metronidazole has not been established. This article reports on a study undertaken to compare the efficacy of quadruple and furazolidone-based triple therapy in the eradication of H. pylori resistant to metronidazole. The study included duodenal ulcer patients (n = 70) in whom initial eradication therapy failed and who harbored H. pylori strains that are resistant to metronidazole. Patients were randomized to receive one of the following 7 day regimens: colloidal bismuth subcitrate, tetracycline, and furazolidone (BTF), or omeprazole, colloidal bismuth subcitrate, tetracycline, and metronidazole (OBTM). Duodenal ulcers were healed in nine of 10 (90 percent) patients in the BTF group and in all patients (12 of 12) in he OBTM group. A significantly lower rate of adverse events was observed in the BTF group than in the OBTM group (31.4 percent versus 60 percent, respectively) but there was no difference in terms of discontinuation of treatment. The authors conclude that the 1 week BTF regimen was as effective as the OBTM regimen, and produced less adverse events. Thus, it may be used in patients in whom resistance of H. pylori to metronidazole is suspected. 3 tables. 22 references.

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Helicobacter Pylori Infection and Gastric Outlet Obstruction: Prevalence of the Infection and Role of Antimicrobial Treatment Source: Alimentary Pharmacology and Therapeutics. 16(7): 1203-1208. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The prevalence of Helicobacter pylori infection in peptic ulcer disease complicated by gastric outlet obstruction seems to be, overall, lower than that reported in noncomplicated ulcer disease, with a mean value of 69 percent. However, H. pylori infection rates in various studies range from 33 percent to 91 percent, suggesting that differences in variables, such as the number and type of diagnostic methods used or the frequency of nonsteroidal anti-inflammatory drug (NSAID) use, may be responsible for the low prevalence reported in some studies. This article reviews these issues, including the prevalence of the infection and the role of antimicrobial treatment. The resolution of gastric outlet obstruction after the eradication of H. pylori has been demonstrated by

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several studies. The beneficial effect of H. pylori eradication on gastric outlet obstruction is observed early, just a few weeks after the administration of antimicrobial treatment. Furthermore, this favorable effect seems to remain during long term follow up. Nevertheless, gastric outlet obstruction does not always resolve after H. pylori eradication treatment and an explanation for the failures is not completely clear. The authors hypothesize that NSAID intake perhaps plays a major role in these cases. Treatment should start pharmacologically with the eradication of H. pylori, even when stenosis is considered to be fibrotic, or when there is some gastric stasis. Dilation or surgery should be reserved for patients who do not respond to medical therapy. 1 table. 29 references. •

Density of Helicobacter pylori Infection in Patients with Peptic Ulcer Perforation Source: Journal of the American College of Surgeons. 186(6): 659-663. June 1998. Summary: The prevalence of severe ulcer complications requiring emergency surgery has not been reduced, despite the common use of H2 receptor antagonists and proton pump inhibitors. This article reports on a study in which Helicobacter pylori (HP) infection and the severity of histologic change was investigated were evaluated semiquantitatively in patients with peptic ulcer who required surgery. The authors reviewed a total of 113 consecutive patients (98 men and 15 women) operated on for perforation, hemorrhage, or stenosis of gastroduodenal ulcer between 1986 and 1995. HP detection was by immunohistochemical staining and the severity of gastritis was evaluated by histologic examination using Rauw's criteria. Although the number of operations for gastroduodenal ulcer declined significantly, the rate of emergency operations for gastroduodenal ulcer increased from 60 to 90 percent, with the result that the frequency of operations for perforation or bleeding remained virtually constant while that for stenosis decreased significantly. HP infection was more prevalent in perforated ulcer (92 percent) than hemorrhagic ulcer (55 percent) or stenotic ulcer (45 percent). The authors conclude that perforated ulcer was associated with significantly more severe HP infection and gastritis changes than hemorrhagic or stenotic ulcer. 4 tables. 33 references. (AA-M).

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Epidemiology of the Antibiotic Resistance of Helicobacter Pylori in Canada Source: Canadian Journal of Gastroenterology. 14(10): 879-882. November 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: The rate of Helicobacter pylori resistance to antibiotics determines the cure rate of treatment regimens containing such antibiotics. This article reports on a review of the literature, undertaken to determine the rates of H. pylori resistance to metronidazole and clarithromycin in Canada, and to determine whether these rates vary in different regions of Canada. Eleven studies that estimated H. pylori resistance to metronidazole and nine studies that estimated resistance to clarithromycin in Canada were identified. Rates of resistance for metronidazole and clarithromycin varied from 11 percent to 48 percent and 0 percent to 12 percent, respectively. Studies that obtained their estimates using the E test and those that did not clearly exclude patients who had undergone previous attempts at H. pylori eradication had higher estimates of resistance, accounting for this variability in results. The author concludes that the prevalence of primary H. pylori resistance in Canada appears to be 18 to 22 percent for metronidazole and less than 4 percent for clarithromycin. These rates appear to be consistent across the

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different regions studied in Canada, but many regions have not been studied. 2 figures. 23 references. •

Effect of Helicobacter Pylori Eradication Therapy on Dyspepsia Symptoms in Industrial Workers in Japan Source: Alimentary Pharmacology and Therapeutics. 15(6): 805-811. June 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The relationship between Helicobacter pylori infection and non ulcer dyspepsia (heartburn, impaired digestion) is still controversial. The potential benefits and risks of the treatment could depend on local conditions, such as the prevalence of the infection and the local rates of gastric (stomach) cancer. This article reports on a study undertaken to evaluate the effects of H. pylori eradication therapy on non ulcer dyspepsia symptoms in industrial workers in Japan. A total of 615 employees of an industrial corporation were examined for H. pylori infection and symptom scores: 215 H. pylori positive non ulcer dyspepsia cases underwent eradication therapy. Symptom scores were also analyzed 12 months after the eradication therapy. Serum pepsinogen A and pepsinogen C levels were analyzed and chronic atrophic gastritis was serologically diagnosed. The symptom score improved significantly in the cured cases, but not in the non cured cases. The authors conclude that in both groups (cases with atrophic gastritis and cases with chronic gastritis only) the cure of H. pylori infection was effective in improving non ulcer dyspepsia symptoms. 1 figure. 3 tables. 35 references.

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Eradication Rates of Clarithromycin-Resistant Helicobacter Pylori Using Either Rabeprazole or Lansoprazole plus Amoxicillin and Clarithromycin Source: Alimentary Pharmacology and Therapeutics. 16(11): 1933-1938. November 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure. This article reports on a study undertaken to compare the eradication rates of triple therapy using amoxicillin (A), clarithromycin (C), and rabeprazole (R) or lansoprazole (L) against clarithromycin-sensitive and clarithromycin-resistant strains of H. pylori. The study included 295 patients who were randomly divided into 4 groups and treated for 1 week: 147 cases were treated with RAC and 148 cases were treated with LAC. According to intention-to-treat and perprotocol analyses, the eradication rates were 88 percent and 91 percent with RAC and 78 percent and 81 percent with LAC, respectively. In addition, the eradication rates for clarithromycin-sensitive strains with RAC and LAC were 98 percent and 89 percent, respectively, and for clarithromycin-resistant strains with RAC and LAC were 8.1 percent and 0 percent, respectively. The authors conclude that the eradication rate was significantly higher with RAC than LAC. The eradication rate for clarithromycinresistant strains was low in both groups and an improved eradication rate could not be achieved by changing the dose of clarithromycin or proton pump inhibitor (PPI). 4 tables. 22 references.

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Increased Gastric Acid Secretion After Helicobacter Pylori Eradication May Be a Factor for Developing Reflux Oesophagitis Source: Alimentary Pharmacology and Therapeutics. 15(6): 813-820. June 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: The role of acid secretion in reflux esophagitis, which may develop after Helicobacter pylori eradication, is not well known. This article reports on a study undertaken to investigate the participation of altered gastric (stomach) acid secretion and the presence of hiatal hernia in the development of reflux esophagitis after eradication therapy for H. pylori. A total of 105 patients with H. pylori infection, but without reflux esophagitis at the time of eradication therapy, were followed prospectively for 7 months after the clearance of this microorganism. Gastric acid secretion was assessed by endoscopic gastrin test and the presence of hiatal hernia was assessed by endoscopy. Reflux esophagitis developed in 11 out of 105 (10.5 percent) patients when examined at 7 months after the eradication therapy. The incidence was correlated significantly with the increase in gastric acid secretion after the eradication of H. pylori and was significantly higher in the patients with hiatal hernia (20 percent) than in those without it (0 percent). The authors conclude that increased acid secretion after H. pylori eradication is an important risk factor of reflux esophagitis, especially in patients with hiatal hernia. 3 figures. 41 references.

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Favourable Effect of an Acidified Milk (LC-1) on Helicobacter Pylori Gastritis in Man Source: European Journal of Gastroenterology and Hepatology. 13(1): 25-29. January 2001. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London SE1 1GB, UK 44(0)20-7940-7502. Fax: 44(0)20-7940-7574. Website: http://www.eurojgh.com/. Summary: The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid independent suppressive effect on Helicobacter pylori in humans. This study investigated the effect of L. johnsonii La1 acidified milk (LC-1) on H. pylori infection in 53 volunteers infected with H. pylori. Volunteers were randomized to received either LC-1 or placebo 180 milliliters twice a day for 3 weeks. All subjects also received clarithromycin 500 milligrams twice a day (bid) during the last two weeks of acidified milk therapy. Esophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4 to 8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. Results showed that LC-1 ingestion induced a decrease in H. pylori density in the antrum (the passage from the esophagus to the stomach, i.e., the first part of the stomach) and the corpus (the body of the stomach). LC-1 also reduced inflammation and gastritis activity in the antrum and of activity in the corpus. Clarithromycin eradicated H. pylori in 26 percent of the subjects; LC-1 did not improve the antibiotic effect. These results suggest that H. pylori infection and gastritis can be down regulated by LC-1. 4 tables. 33 references.

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Review Article: Invasive and Non-Invasive Tests for Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 13-22. October 2000.

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Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: There are two general ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or a noninvasive procedure. This article reviews the current thinking on the use of these tests. The invasive procedures involve an endoscopy and biopsy. A biopsy is essential because often the mucosa may appear macroscopically normal but nevertheless be inflamed. A biopsy is obtained by histological examination, culture, polymerase chain reaction (PCR), or detection of the presence of urease activity in biopsy material. The noninvasive tests that can be used to diagnose the infection are serology (blood tests); detection of labeled metabolic products of urea hydrolysis in the breath, the urine, or the blood; and detection of H. pylori antigen in a stool specimen. The authors conclude that at present, no single test can be relied upon to detect definitely colonization by H. pylori, and a combination of two is recommended if this is feasible. The choice of the test to be used is not straightforward and may vary according to the clinical condition and local expertise. 8 tables. 95 references. •

Helicobacter Pylori Eradication and its Implications for the Future Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 103-107. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article addresses the eradication of Helicobacter pylori infections in humans. The rationale for eradicating H. pylori infection is its causal role in gastric malignancies and peptic ulcer disease. However, H. pylori are highly diverse and at least part of this variation involves characteristics related to pathogenicity. A large amount of evidence suggests that H. pylori infection of humans is ancient, and in general, the interaction is not terribly destructive. Current evidence indicates that fewer than 20 percent of all infected persons will develop any clinical consequences from their infection. However, the author stresses the need for better understanding of the risks associated with infection with particular H. pylori strains, and for limiting treatment to those situations in which the indications for eradicating H. pylori are clear cut. It is entirely possible that some H. pylori strains are commensals, and that others are symbionts. Eradicating those infections could ultimately cause more harm than good. The author concludes that it is too early to reach firm conclusions about whether all H. pylori infections need to be eradicated. 2 tables. 26 references. (AA-M).

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Transmission of Helicobacter Pylori from Stomach to Stomach Source: Alimentary Pharmacology and Therapeutics. 15(Supplement 1): 33-42. June 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article considers the mode of transmission of Helicobacter pylori, at present largely unknown and a matter of circumstantial evidence and speculation rather than fact. However, the principle evidence is of two sorts: the epidemiological data, providing evidence of possible risk factors associated with transmission, and the

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identification of potential sources from which H. pylori could be acquired. Evidence exists for several potential sources of infection and several possible modes of transmission, and it is feasible that the transmission of H. pylori varies according to the cultural and demographic circumstances. The author considers age factors, ethnicity, and socioeconomic factors. However, the most likely recognized source for H. pylori is the human stomach, although it is not known by what route the organism is transmitted to the stomach. The author reviews the evidence for the gastro oral route of transmission, fecal route and environmental sources, occupational exposure in hospitals, and food source animals and pets as a reservoir of infection. Evidence suggests close personal contact is important and that acquisition occurs mainly in childhood. 103 references. •

Role of Helicobacter Pylori Infection in Non-Ulcer Dyspepsia Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 63-69. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article considers the role of Helicobacter pylori infection in nonulcer dyspepsia. The author notes that it is currently unclear whether H. pylori infection plays a role in patients who fulfill the criteria for nonulcer dyspepsia. The author reviews evidence for H. pylori-induced changes in gastric emptying, gastrointestinal motility, gastric acid secretion, and gastric perception in patients with nonulcer dyspepsia. Problems in study design and execution of nonulcer dyspepsia treatment trials are covered. The author reviews the results of nonulcer dyspepsia treatment trials which have been performed in H. pylori-positive patients. To date, none of these studies has convincingly shown that cure of the H. pylori infection leads to a sustained improvement in symptoms. There is agreement that H. pylori infection does cause changes in gastric physiology. 55 references. (AA-M).

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Resistance of Helicobacter Pylori to Antibiotics Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 43-53. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article describes the resistance of Helicobacter pylori to antibiotics, a major reason for failure of the current regimens used to eradicate H. pylori. The author stresses that the definition of resistance is not simple, and the clinical relevance of in vitro results must be considered. The different methods of testing antibiotics cannot apply in all cases. Resistance to clarithromycin has a low prevalence rate (less than 10 percent) and its mechanism is well defined. Its clinical relevance is not questioned and, because of a clear occurrence of a bimodal strain population, the method for detecting resistance is not crucial. Resistance to nitroimidazoles is much more common, probably in the range of 30 percent or more in Europe. Neither the mechanism of action of metronidazole resistance nor its mechanism is well known. Metronidazole resistance was found to be clinically relevant when standard triple therapy was used. The relevance is questioned for triple therapies including a proton pump inhibitor, clarithromycin and metronidazole. More clinical data are needed in this field and the use of agar dilutions is recommended to assess the susceptibility of H. pylori to metronidazole. The mechanism of resistance to quinolones has been described but these

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compounds are not currently used for H. pylori infection. No resistance has yet been described for amoxycillin but continuous surveillance is needed in order to detect new cases, as was recently the case for tetracycline resistance. 2 figures. 5 tables. 39 references. (AA-M). •

Breath Testing in Health and Disease: Lactose Maldigestion, Bacterial Overgrowth, Intestinal Transit Time and Helicobacter Pylori Infection Source: Practical Gastroenterology. 23(4): 72, 74, 76, 78, 80. April 1999. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: This article describes the use of breath testing, a convenient and reliable method of evaluating lactose maldigestion, bacterial overgrowth, intestinal transit time, and H. pylori infection. These tests are inexpensive, noninvasive, and present little risk to the patient. The normal colonic flora produces hydrogen (H2) gas from food processed in the gastrointestinal tract. A portion of the H2 is absorbed and excreted by the lungs. In bacterial overgrowth, the bacteria are located more proximally and expired H2 will increase sooner after ingestion of food. Maldigested lactose, present in lactose intolerant patients, provides more substrate and consequently increases expired H2. Helicobacter pylori bacteria produce an urease that hydrolyzes urea producing carbon dioxide. If radiolabeled urea is given to a patient with an active infection, radiolabeled CO2 will be discharged from the lungs. The authors conclude that breath testing is an effective diagnostic aid that is well suited for the gastroenterologic and primary care clinic. 7 references.

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Understanding Disease Outcome Following Acquisition of Helicobacter Pylori Infection During Childhood Source: Canadian Journal of Gastroenterology. 13(3): 229-234. April 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Summary: This article discusses disease outcome following acquisition of Helicobacter pylori infection during childhood. The article is taken from a presentation at the Canadian Helicobacter Pylori Consensus Conference held in June 1998 in Ottawa, Ontario. H. pylori causes chronic active (type B) gastritis in the overwhelming majority of infected individuals. Current research activities center around the relative contribution of virulence factors in the bacterium and host responses to the microbial infection in determining which subjects will go on to develop complications. These can include peptic ulceration, gastric cancers, and gastric lymphomas. The authors conclude that a likely possibility is that both the virulence of the infecting organism (H. pylori) and the host response to infection work in concert to determine which people will remain asymptomatic throughout their lifetime and which will develop complications. The authors call for the development of a reproducible model of peptic ulcer disease in an animal model of H. pylori infection. 2 tables. 75 references.

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Reinfection Versus Recrudescence in Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 55-61. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected].

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Summary: This article explores reinfection versus recrudescence in Helicobacter pylori infection. Reinfection is defined as the acquisition of a new infection and recrudescence as the event of reappearance of H. pylori although initial posttreatment assessment tests were negative. Antimicrobial treatment of H. pylori is the proper management strategy in patients with ulcers. A high rate of H. pylori reinfection after successful eradication therapy however, may give rise to ulcer recurrence. The risk of reinfection, depending on the prevalence and the rate of acquisition of H. pylori infection, varies with socioeconomic status, age, and geographical location. The rate of reinfection may vary in a similar way. The available data in the literature reveal that reinfection by H. pylori is low or absent in developed countries and may be lower than the initial rate of acquisition. In addition, reported cases of H. pylori reinfection are often cases of recrudescent H. pylori infection. Acquisition rate in developing countries is high, so the reinfection rate is expected to be higher than in developed countries. However, studies discriminating reinfection from recrudescence are lacking. Therefore, more data from developing regions are needed to settle if 'cured once, cured forever' holds true. 1 figure. 1 table. 68 references. (AA-M). •

Review Article: Is Helicobacter Pylori Status Relevant in the Management of GORD? Source: Alimentary Pharmacology and Therapeutics. 14(Supplement 3): 31-42. October 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This article explores the growing interest in the relationship between Helicobacter pylori infection and gastroesophageal reflux disease (GERD). The authors note that this relationship is complex, as yet not fully clear, and probably based on multiple factors. The prevalence of H. pylori infection in patients with GERD is similar, but more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GERD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GERD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GERD. Patients after H. pylori eradication may develop GERD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and preexisting GERD. Long term therapy of GERD in patients infected with H. pylori may lead to rapid progression of atrophic gastritis (stomach inflammation), intestinal metaplasia and dysplasia, and increase the risk of developing gastric (stomach) cancer. More recently, it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GERD. The authors propose that the progression of gastritis depends on the threshold of acid output at which H. pylori can flourish. Any decrease of acid secretion changes the behavior of H. pylori. During proton pump inhibitor (PPI) treatment, H. pylori redistribution occurs within the stomach. The authors also discuss Barrett's esophagus, as growing evidence is compiled on the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's esophagus patients is not different from that exhibited by controls, roughly one third of the subjects. Intestinal metaplasia (overgrowth) of the gastric cardia (the proximal part of the stomach) seems to be equally frequent in patients with and without GERD. The authors conclude that it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's associated adenocarcinoma. 1 figure. 100 references.

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Helicobacter Pylori and Peptic Ulcer Disease: Bridging the Gap Between Knowledge and Treatment Source: Postgraduate Medicine. 103(3): 231-234, 236-238, 243. March 1998. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article looks at the latest diagnostic techniques and therapies used to identify and treat Helicobacter pylori associated peptic ulcer disease, with an emphasis on cost-effectiveness and patient compliance. H. pylori is widely accepted as the pathogenic cause of peptic ulcer disease, and studies show that its eradication cures infected patients. Combination antimicrobial therapy has been successful in not only curing the disease, but also significantly decreasing recurrence. However, only about one third of primary care physicians prescribe this therapy. Primary care physicians who do prescribe the treatment must better educate patients regarding compliance with the dosing schedule as well as the benefits of treatment. For example, patients should be advised that although the dosing schedule may be demanding, the treatment duration is short and the side effects are generally tolerable. Physicians may further motivate patients by explaining that once they have successfully completed treatment, they should be symptom-free with a low risk of ulcer recurrence. 3 tables. 32 references. (AAM).

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Update on Testing and Treatment for Helicobacter Pylori in Primary Care Patients with Uninvestigated Dyspepsia Source: Practical Gastroenterology. 26(3): 42,45-47, 50,52. March 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This article offers an update on the testing and treatment for Helicobacter pylori in patients with dyspepsia (heartburn), a prevalent condition often seen in primary care practice. Multiple practice guidelines endorse testing and treatment for H. pylori as the initial step in the management of patients with uninvestigated dyspepsia. Recent clinical trials have provided support for this 'test and treat' approach over prompt endoscopy by demonstrating comparable clinical outcomes between these two strategies, with reduced costs and endoscopy rates with the test-and-treat strategy, but a slight compromise in patient satisfaction. The test-and-treat strategy appears to be costeffective even though many patients with dyspepsia have non-ulcer dyspepsia, in which H. pylori eradication yields little or no benefit. This cost-effectiveness advantage is explained in large part by the avoidance of endoscopy without adverse consequences in a large fraction of patients. Remaining questions include whether the test-and-treat strategy results in long-term cost savings, and how patient satisfaction and costeffectiveness should be balanced against each other in the care of patients with uninvestigated dyspepsia. 1 figure. 1 table. 13 references.

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From Bench to Bedside to Bug: An Update of Clinically Relevant Advances in the Care of Persons with Helicobacter Pylori-Associated Diseases Source: Canadian Journal of Gastroenterology. 14(3): 188-198. March 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected].

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Summary: This article presents an update of clinically relevant advances in the care of patients with Helicobacter pylori associated diseases. The information was compiled after meetings at the XIth International Workshop on Gastroduodenal Pathology and Helicobacter Pylori (September 1998, Budapest, Hungary). The mode of transmission of H. pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer. The role of H. pylori eradication in persons with uninvestigated dyspepsia remains controversial. New clinical trials of H. pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer like or reflux like dyspepsia. Clearly, the move is toward symptom based management of persons with dyspepsia, with fewer endoscopies being needed in otherwise healthy young patients with dyspepsia. It remains controversial whether eradicating H. pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease. The 1 week proton pump inhibitor based triple regimens remain the gold standard of H. pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80 percent H. pylori eradication rate on an intention to treat basis. While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H. pylori infection. The number of H. pylori associated gastroduodenal diseases grows to include possible liver, vascular, immune, and skin conditions. 2 tables. 157 references. •

Treatment of Helicobacter Pylori Infection Source: BMJ. British Medical Journal. 320(7226): 31-34. January 1, 2000. Contact: Available from BMA House. BMJ Fulfilment Department, Tavistock Square, London WC1H 9TD. 44(0)171 383 6270. E-mail: [email protected]. Summary: This article provides a basic framework for the treatment of Helicobacter pylori infection. The authors base their recommendations on basic bacteriological principles and on a regularly updated in-house database of all published therapeutic studies. The authors maintain that treatment to eradicate H. pylori in patients with a proved ulcer is both cost effective and benefits the patient and society. Several equally effective regimens are available, but even the best fail in 5 to 20 percent of patients. Antibiotic resistance is usually induced after failure, and initial regimens should not compromise future therapeutic possibilities. The authors recommend that physicians should choose two complementary regimens, which when used consecutively come close to 100 percent cure. Treatment should start with a regimen based on clarithromycin with a backup regimen based on metronidazole unless resistance is above 15 percent, in which case the order of therapies should be reversed. Triple regimens that combine clarithromycin and metronidazole should not be used as there is no valid empirical backup regimen after failure. In general, the likelihood of cure can be increased by increasing the length of treatment. 2 figures. 1 table. 30 references.

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Clinical Presentation of Helicobacter Pylori-Positive and-Negative Functional Dyspepsia Source: Journal of Gastroenterology and Hepatology. 15(5): 498-502. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com.

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Summary: This article reports on a study in which a questionnaire was used to record the clinical presentation of functional dyspepsia (heartburn) in relation to Helicobacter pylori infection in a consecutive series of patients sent for upper gastrointestinal endoscopy. Only patients without macroscopic abnormalities in their esophagus, stomach, and duodenum were included. The study questionnaire included two questions related to daily life, and the calculation of a symptoms score. In the study, 222 patients were H. pylori positive and 182 patients were H. pylori negative. Loss of weight was significantly more common in the H. pylori positive group. Patients with H. pylori infection had a significantly higher overall symptom score compared with H. pylori negative subjects. In addition, the severity of epigastric and nocturnal pain, heartburn, retrosternal (behind the breastbone) heartburn, and vomiting was significantly higher in H. pylori positive functional dyspeptic patients, and the influence on daily life and activities was significantly worse. The authors conclude that the combination of retrosternal pain, weight loss, food intolerance, and the absence of halitosis signified a 64 percent accuracy in predicting H. pylori infection. Although it was not possible to differentiate between H. pylori positive and H. pylori negative functional dyspeptics on the basis of clinical presentation and the number of complaints, overall symptom score and severity of several symptoms was significantly higher in the H. pylori positive group. 3 tables. 23 references. •

Treatment of Helicobacter Pylori Infection in Clinical Practice in the United States: Results from 224 Patients Source: Digestive Diseases and Sciences. 45(2): 265-271. February 2000. Summary: This article reports on a study that explored treatment success, compliance, and side effects for treatment of Helicobacter pylori in clinical practice. In all, 224 consecutive patients received H. pylori treatment: 97 received 2 weeks of bismuth subsalicylate, metronidazole, tetracycline four times a day with a H2 receptor antagonist twice a day (BMT); 89 received 1 week of metronidazole, lansoprazole, and clarithromycin twice a day (MLC); and 38 received 1 week of BMT with lansoprazole twice a day (BMT PPI). Cure rates were: BMT 81 percent, MLC 90 percent, and BMT PPI 87 percent. More patients who were prescribed a bismuth based regimen discontinued medications due to side effects, compared to MLC. Nausea was more common for BMT compared to MLC. In conclusion, treatment of H. pylori infection with a 1 week course of MLC achieves a high rate of cure in clinical practice. 5 tables. 40 references.

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Role of Antisecretory Drugs in the Treatment of Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 21-25. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article reviews the role of antisecretory drugs in the treatment of Helicobacter pylori infection. The author notes that the efficacy of antibiotics against H. pylori is enhanced by the coadministration of antisecretory drugs. While proton pump inhibitors appear to have some direct effect on H. pylori and extreme hypochlorhydria has a deleterious effect on the organism, the most likely mechanism by which antisecretory drugs as a class provide this effect is by improving the efficacy of the antibiotics themselves. Although proton pump inhibitors are the most widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic effects. The author concludes that it is possible to cure H. pylori infection with regimens that do not include

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antisecretory drugs. However, the addition of antisecretory drugs enhances the efficacy of almost all such regimens and, in patients with active peptic ulcers, speeds the relief of symptoms. The mechanisms by which antisecretory drugs enhance antimicrobial efficacy have not been clearly determined but are probably multiple. 3 tables. 36 references. (AA-M). •

Non-Endoscopic Tests in the Diagnosis of Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 11-20. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This article reviews the use of nonendoscopic tests in the diagnosis of Helicobacter pylori infection. The author notes that upper gastrointestinal endoscopy is expensive, uncomfortable for patients, and carries a small but finite risk. Nonendoscopic tests are cheaper and more convenient, and thus should be preferred in situations where the extra information yielded by an endoscopy is not needed. In this article, the two main types of noninvasive tests, urea breath tests (UBT) and antibody detection tests, are described, with special reference to recent advances. Other noninvasive tests are briefly mentioned, and finally, the place of noninvasive tests in treatment trials and clinical practice is discussed. For the UBT, either nonradioactive 13C or radioactive 14C is used as an isotopic marker. 14C-UBTs are cheaper and are safe, but licensing regulations may make them inconvenient. Some UBTs have been simplified by omitting the normal test meal and encapsulating the urea to avoid metabolism by oral bacteria. These modified tests need further validation, especially when used for assessing H. pylori status after treatment. Serological tests detect circulating IgG or IgA. They are of variable accuracy, the best performing as well as UBTs. Paired serum samples pretreatment and 6 months posttreatment accurately assess treatment success. Rapid inoffice tests appear less accurate and cannot be used for posttreatment assessment. In practice, for primary diagnosis of H. pylori infection, endoscopic tests are best because endoscopy allows assessment of treatment indications. Where indications already exist or taking biopsies is dangerous, UBTs or serology are suitable, but serology is cheaper and more convenient. After treatment, endoscopy is usually unnecessary and UBTs accurately assess H. pylori status at 4 weeks. Serology is an alternative only if results are not required before 6 months. 107 references. (AA-M).

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Treatment Strategies for Helicobacter Pylori Infection Source: American Family Physician. 55(8): 2765-2774. June 1997. Summary: This article updates readers on treatment strategies for Helicobacter pylori infection. Peptic ulcer disease is strongly associated with infection by H. pylori; more than 90 percent of duodenal ulcers and adenocarcinomas of the distal stomach are associated with H. pylori infection. Eradication of the organism effectively prevents relapses of gastroduodenal ulcers associated with H. pylori. In patients undergoing endoscopy, the rapid urease test is highly sensitive and specific in diagnosing H. pylori infection. Noninvasive diagnostic methods include serologic antibody measurements and urea breath testing. Empiric therapy may be tried if the diagnosis is suspected on a clinical basis. Traditional 14 day triple therapy with bismuth, metronidazole, and either amoxicillin or tetracycline has consistently produced eradication rates of approximately 90 percent. Compliant patients who suffer side effects after 1 week of therapy can stop treatment. Those who have not completed 1 week of therapy should be switched to an

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alternate regimen. Newer combination regimens have shown promise in a smaller number of studies. No single agent given as monotherapy has proved to be acceptably effective in clinical studies. 3 figures. 2 tables. 34 references. (AA-M). •

Helicobacter Pylori Eradication Did Not Change Ulcer Recurrence or Dyspepsia Rates in Patients Who Used NSAIDs (commentary) Source: ACP Journal Club. 130(2): 38. March-April 1999. Contact: Available from American College of Physicians-American Society of Internal Medicine (ACP-ASIM). 190 North Independence Mall West, Philadelphia, PA 191061572. Summary: This brief article offers a summary of a recent research study, with an accompanying commentary. The study was undertaken to determine whether Helicobacter pylori eradication in patients who use nonsteroidal antiinflammatory drugs (NSAIDs) can decrease dyspepsia (heartburn) without affecting the ulcer recurrence rate. The study comprised 285 patients who were 18 to 85 years of age, who required NSAID treatment, who had H. pylori infection of the gastric mucosa, who had peptic ulcers at baseline or in the previous 5 years, or who had moderate or severe NSAID associated dyspepsia. Patients were allocated to H. pylori eradication treatment twice a day with omeprazole, amoxicillin, and clarithromycin (n = 142) or to control treatment twice a day with omeprazole and placebo antibiotics (n = 143) for 1 week. All patients subsequently received omeprazole until endoscopy at week 4. No difference was found between groups in the number of patients who had treatment failure during followup. Fewer patients in the eradication group than in the control group were free of ulcers at 8 weeks (89 percent versus 100 percent). The author concluded that in patients who used NSAIDs, H. pylori eradication did not influence the rates of ulcer recurrence or dyspepsia over 6 months. The commentary discusses the results and concludes that it could still be argued that eradicating H. pylori is worth considering before ulcers form in patients who are about to start taking NSAIDs. 1 table. 1 reference.

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Helicobacter Pylori Infection in Nonulcer Dyspepsia: To Treat or Not to Treat? Source: Consultant. 39(2): 416. February 1999. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: This brief article summarizes two recent studies of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. The author notes that the results of these studies are contradictory. In the first study (McColl et al., 1998) the authors suggest that all patients with H. pylori infection and nonulcer dyspepsia be treated with omeprazole plus antibiotics, since it is not possible to predict which patients might benefit. In the second study (Blum et al., 1998) the rate of symptom relief among those with persistent H. pylori infection who had been given omeprazole and antibiotics was similar to that in persons in whom the infection was eliminated. The authors of this study remark that the role of H. pylori in nonulcer dyspepsia is still unclear and conclude that although the eradication of H. pylori infection may help prevent or cure peptic ulcer disease, it is not likely to relieve symptoms in patients with nonulcer dyspepsia. The author of this summary reports that consensus statements recommend diagnostic endoscopy for patients older than 45 years with dyspepsia, or patients of any age with unexplained weight loss, vomiting, dysphagia (swallowing difficulty), gastrointestinal bleeding, or anemia. Endoscopy is also recommended for patients of any age with dyspepsia who have a heightened risk of gastric cancer based on their

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ethnic, socioeconomic, or familial background. For patients younger than 45 years, the recommended approach is to perform serologic tests for H. pylori and prescribe eradication therapy for those with positive results. In all instances, dietary, emotional, and environmental triggers of nonulcer dyspepsia should be identified and managed. 3 references. •

Gastric Biopsy-Based Rapid Urease Tests for the Detection of Helicobacter Pylori: Progress, Advantages and Limitations. (editorial) Source: Journal of Gastroenterology and Hepatology. 17 (6): 629-632. June 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This editorial comments on a study reported in this same issue of the Journal of Gastroenterology and Hepatology on the use of gastric (stomach) biopsy-based rapid urease tests for the detection of Helicobacter pylori. The gastric biopsy based rapid urease test has many advantages over other invasive methods: the test is simple to perform and the results are easy to read; the test is relatively inexpensive; and the test provides a prompt result (positive results occur within 1 hour in 53 to 99 percent of cases with H. pylori infection, allowing the initiation of the therapy soon after endoscopy for these cases). However, the gastric biopsy-based rapid urease tests also suffer from several limitations: they are invasive; they are not accurate in monitoring the effectiveness of eradication therapy; and less accurate results (including false-negative results) may occur, particularly in patients who are receiving treatment with antimicrobial agents or antisecretory drugs, in patients with bleeding peptic ulcers, and in children or the elderly. 1 table. 47 references.

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Interactions Between Helicobacter Pylori and Gastroesophageal Reflux Disease Source: Diseases of the Esophagus. 11(4): 203-209. October 1998. Contact: Available from Harcourt Brace and Company, Ltd. Journal Subscription Department. Foots Cray, Sidcup, Kent, DA 14 5HP. Summary: This literature review explores the relationship between Helicobacter pylori and gastroesophageal reflux disease (GERD). The authors begin by noting the differences in nomenclature, particularly between European and American researchers; European terminology is used in this article. The authors discuss the research articles and summarize their conclusions. H. pylori colonization rates do not differ between patients with uncomplicated GERD and controls. Eradication of H. pylori infection in patients with duodenal ulcer disease may provoke the development of reflux esophagitis. Cardiac mucosa is as susceptible to H. pylori infection as antral and corpus mucosa. An inflammatory cell response to infection in cardiac mucosa is similar to that observed in antral mucosa. In patients with Barrett's esophagus, H. pylori infects gastric epithelium but not intestinal epithelium. In patients without endoscopic Barrett's esophagus, intestinal metaplasia at the gastroesophageal junction may result from H. pylori infection. 2 tables. 72 references.

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H. Pylori, GERD Should Be Treated As Separate Conditions Source: Gastroenterology and Endoscopy News. p. 7. January 2000. Contact: Available from McMahon Publishing Group. 545 West 45th Street, 8th Floor, New York, NY 10036. (212) 957-5300. Website: www.gastroendonews.com.

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Summary: This news article reports on soon to be published studies that support the contention that Helicobacter pylori infections and gastroesophageal reflux disease (GERD) should be treated as separate conditions. The article stresses that the relationship between H. pylori and GERD is complex and controversial. Epidemiologic evidence supports a protective role of H. pylori in GERD; the prevalence of H. pylori in patients with GERD is about 10 percent lower than in controls, and H. pylori positive patients are more likely to present with fewer cases of esophagitis than those who are H. pylori negative. Additional studies of H. pylori therapy suggest that eradication of the organism causes an increase in the incidence of GERD, but those studies have been challenged. The article refers to a study of a group of patients with active gastric and duodenal ulcers in which heartburn was decreased after 6 months of eradication therapy. The researcher interviewed concludes that H. pylori must be eradicated before initiating long term treatment of reflux esophagitis; however, reflux esophagitis will not necessarily increase after eradication. •

Helicobacter Pylori and the Risk and Management of Associated Diseases: Gastritis, Ulcer Disease, Atrophic Gastritis and Gastric Cancer Source: Alimentary Pharmacology and Therapeutics. 11(Supplement 1): 71-88. April 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: This review article addresses the role of Helicobacter pylori and the effect of H. pylori eradication on gastritis, peptic ulcer disease, atrophic gastritis, and gastric cancer. The author emphasizes the various factors that influence the clinical course of this infection. H. pylori induces chronic gastritis in virtually all infected subjects. This inflammation can lead to peptic ulceration and atrophic gastritis in a considerable number of infected subjects. A minority eventually develops gastric cancer. The risk of such complications depends upon the severity of gastritis, which is determined by various host-and bacteria-related factors. Among bacterial factors, most of the evidence addresses the cagA pathogenicity island, the presence of which has been associated with more severe gastritis, peptic ulceration, atrophic gastritis, and gastric cancer. Among host factors, most of the evidence focuses on acid production in response to H. pylori infection. An increase in acid secretion limits H. pylori gastritis to the antrum at the risk of duodenal ulcer disease; a reduction allows more proximal inflammation at the risk of atrophic gastritis, gastric ulcer disease, and gastric cancer. Gastritis and atrophy negatively influence acid secretion. H. pylori eradication is required in peptic ulcer disease and may be advocated in patients on profound acid suppressive therapy; it has been shown to cure gastritis and prevent ulcer recurrence. The author concludes that further study is required to determine the efficacy of H. pylori eradication in the primary and secondary prevention of atrophic gastritis and gastric cancer. 3 figures. 193 references. (AA).

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Gastric Cancer and Helicobacter Pylori Source: Alimentary Pharmacology and Therapeutics. 16 (Supplement 4): 83-88. July 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com.

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Summary: This review article discusses gastric (stomach) cancer, the second most common cause of death from malignancy in the world. The pathogenesis of stomach cancer is comparatively well understood and its etiology (cause) multifactorial. Noncardia gastric cancer usually arises in a stomach that has been inflamed over a long period and where atrophy and intestinal metaplasia have supervened. The most common cause of gastric inflammation is infection with Helicobacter pylori. Colonization with this organism increases the relative risk of developing stomach cancer by about six. The likelihood of stomach cancer increases with the severity and extent of the gastritis. Severity is influenced by the virulence of the infecting organism, the genetics of the host, bile reflux, dietary factors, and the presence of hypochlorhydria which influences the extent, as well as the severity, of the inflammation. The only predisposing factor which can easily be manipulated is H. pylori infection, which can be successfully treated in 80 to 90 percent of cases using a 1 week therapeutic regimen. 1 table. 27 references. •

Review Article: The Control of Gastric Acid and Helicobacter Pylori Eradication Source: Alimentary Pharmacology and Therapeutics. 14(11): 1383-1401. November 2000. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: This review article focuses on the gastric (stomach) acid pump as a therapeutic target for the control of acid secretion in peptic ulcer and gastroesophageal reflux disease (GERD). The mechnism of the proton pump inhibitors (PPT) is covered as well as their clinical use. The biology of Helicobacter pylori as a gastric resident is then discussed, with special regard to its mechanisms of acid resistance (i.e., how it survives in the seemingly hostile environment of stomach acid). The authors explore the properties of the products of the urease gene clusters, ureA, B, and uerI, E, F, G, and H, in order to explain the unique location of this pathogen. The dominant requirement for acid resistance is the presence of a proton gated urea transporter, UerI, which increases access of gastric juice urea to the intrabacterial urease 300 fold. This enables rapid and continuous buffering of the bacterial periplasm, allowing acid resistance and growth at acidic pH in the presence of urea. The authors also present a hypothesis for the use of combination therapy to eradicate H. pylori infections. 11 figures. 58 references.

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Is a One-Week Course of Triple Anti-Helicobacter Pylori Therapy Sufficient to Control Active Duodenal Ulcer? Source: Alimentary Pharmacology and Therapeutics. 15(7): 1037-1045. July 2001. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Triple therapy currently forms the cornerstone of the treatment of patients with Helicobacter pylori positive duodenal ulcer. This article reports on a study undertaken to establish whether prolonged antisecretory therapy is necessary in patients with active duodenal ulcer. A total of 77 patients with H. pylori positive duodenal ulcer were included in the prospective, controlled, double blind study. All patients received a 7 day treatment with omeprazole 20 milligrams twice daily (b.d.), clarithromycin 500 milligrams b.d., and amoxicillin 1000 milligrams b.d. Patients in the omeprazole group underwent an additional 14 day therapy with omeprazole 20 milligrams; patients in the placebo group received placebo. Endoscopy was performed

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upon inclusion in the study and after 3 and 8 weeks. After 3 weeks, the healing rate was 89 percent in the omeprazole group and 81 percent in the placebo group. After 8 weeks, the ulcer healed in 97 percent of the patients in the total group. H. pylori was eradicated in 88 percent of patients in the omeprazole group and in 91 percent in the placebo group. No statistically significant differences between the groups were found in ulcer related symptoms or in ulcer healing. The authors conclude that in patients with H. pylori positive duodenal ulcer, a 7 day triple therapy alone is sufficient to control the disease. 5 figures. 3 tables. 18 references. •

Outcomes Research in Helicobacter Pylori Infection Source: Alimentary Pharmacology and Therapeutics. 11(supplement 1): 95-101. February 1997. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. E-mail: [email protected]. Summary: While the medical community has accepted the role of H. pylori in the pathogenesis of peptic ulcer disease, confusion persists among clinicians regarding when and on which patients to attempt H. pylori eradication. This article explains the role of outcomes research in helping clinicians to identify which patients benefit from H. pylori eradication and to determine the cost-effective strategies for their diagnosis, treatment, and follow up care. Economic evaluation of the impact of H. pylori infection has focused primarily on assessment of the patient with documented peptic ulcer disease, with particular attention to costs of pharmaceuticals. However, drug costs are only one portion of the total costs of management for patients with acid-related disorders and therefore must be put in the appropriate context. Additional aspects of patient benefit (e.g., patient satisfaction) and health care expenditures (e.g., over the counter medications, specialist visits, hospitalizations) must be included in an evaluation of the value of a particular diagnostic test, treatment, clinical guideline, or disease management strategy. As a result of the high quality and quantity of data emerging, the author concludes that H. pylori eradication is cost effective in selected patient populations: newly documented peptic ulcer disease; history of peptic ulcer disease and taking maintenance therapy; and suspected peptic ulcer disease using a serological test to guide initial treatment. The role of eradication in other areas, for example, patients with nonulcer dyspepsia and screening to prevent gastric cancer, remains to be seen. In addition to the performance of rigorous studies, researchers must respond to the 'information overload' on busy clinicians, by effectively disseminating their findings. If data generated from outcomes research are not integrated into everyday clinical practice, the enormous benefits associated with H. pylori eradication will not be achieved. 1 figure. 19 references. (AA-M).

Federally Funded Research on Helicobacter Pylori The U.S. Government supports a variety of research studies relating to Helicobacter pylori. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable

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

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database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Helicobacter pylori. 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 Helicobacter pylori. The following is typical of the type of information found when searching the CRISP database for Helicobacter pylori: •

Project Title: A NOVEL METHOD TO DETECT HELICOBACTER PYLORI IN CHILDREN Principal Investigator & Institution: Wagner, David A.; Metabolic Solutions, Inc. 460 Amherst St Nashua, Nh 03063 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): In the avalanche of publicity surrounding H. pylori infection, children have been the one segment of the population that has been virtually ignored. However, there is a growing body of evidence that children, and especially minority children, are commonly afflicted with this disease. There are no FDA approved tests, other than the onerous endoscopic-based tests, to detect active H. pylori in children. We intend to address this need for a simple, minimally invasive and accurate diagnostic test for children. Metabolic Solutions has developed a test to determine the presence of active H. pylori infection that we named the Ez-HBT(TM). Although this is a blood test it should not be confused with serology tests that detect the presence of antibodies. The Ez-HBT(TM) is superior to antibody based tests because it detects the presence of gastric urease activity. Urease activity is only present when H. pylori have colonized the stomach. The test begins with the patient ingesting an oral dose of 13Curea (non-radioactive label). The enzyme urease associated with gastric H. pylori breaks urea down into 13CO2 and ammonia. This results in an increase in the ratio of 13C/12C in blood carbon dioxide if H. pylori are present in the stomach. H. pylori infection impairs a child's growth, ability to function in school and may have long term implications for gastric cancer. The simplicity of the Ez-HBT(TM) including no test meal, a tablet that can be dissolved in a glass of water and a single traditional venipuncture makes it an ideal and cost effective tool for identifying H. pylori infection in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACETONE METABOLISM IN HELICOBACTER PYLORI Principal Investigator & Institution: Hoover, Timothy R.; Microbiology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Helicobacter pylori is a major human pathogen that colonizes the gastric mucosa, leading to gastric inflammation that can progress to chronic gastritis, peptic ulcer, gastric cancer or mucosal-associated lymphoma. The ability of H. pylori to establish a chronic infection in the human stomach indicates that it is well adapted to acquire the nutrients it needs for growth in this unique environment. Complete genomic sequences for two unrelated H. pylori strains, 26695 and J99, have greatly aided the understanding of the physiology of this bacterium. Both sequenced

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strains were reported recently to have the genes for a potential acetone carboxylase, an enzyme that initiates the metabolism of acetone by converting it to acetoacetate. Acetone is produced in the body upon the spontaneous decarboxylation of acetoacetate, one of the ketone bodies produced by the liver and used as an energy source when glucose is not readily available. Ketones are always present in the blood, with up to 185 grams of ketone bodies produced per day by the liver of a healthy adult. This proposal will test the hypothesis that H. pylori utilizes acetone as an important energy source for the bacterium in the gastric mucosa. The first specific aim of the proposal is to verify that H. pylori has a functional acetone carboxylase by expressing the protein in Escherichia coli, purifying it, and examining its ability to catalyze the carboxylation of acetone. The second specific aim is to determine if this enzyme is needed by H. pylori to establish a chronic infection in the gastric mucosa. The operon encoding the H. pylori acetone carboxylase will be disrupted and the resulting mutant strain will be examined for its ability to colonize the stomachs of mice and Mongolian gerbils. The proposed studies will expand knowledge of metabolic pathways in H. pylori, which will lead to a better understanding of how this pathogen establishes infections in humans and may provide new strategies for the prevention or treatment of H. pylori infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACID INDUCIBLE RESPONSES IN H PYLORI Principal Investigator & Institution: Mcgowan, Catherine C.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): Helicobacter pylori are curved Gram-negative bacteria that are now recognized as the cause of chronic superficial gastritis in humans, and this organism plays an important etiologic role in the pathogenesis of peptic ulcer disease and distal gastric adenocarcinoma. H. pylori colonizes the mucus layer overlying the gastric epithelium, where it is exposed to a wide range of pH values. Urease activity is required for H. pylori survival at low pH, and its presence is essential for colonization. However, little else is known about the mechanisms which allow H. pylori to survive in acidic environments. In previous studies, the investigators have used the strategy of subtractive RNA hybridization to identify an acid-inducible gene in H. pylori, wbcJ, that is essential for O-antigen expression and which contributes to acid survival of the organism. The long-term goal of this study is to isolate and identify additional acid-inducible factors in H. pylori which are required for establishment and maintenance of infection. The hypothesis of this study is that H. pylori possesses a regulated, inducible acid stress response system. The specific aims are 1) to study the transcriptional regulation of the acid-inducible H. pylori gene, wbcJ and to characterize its role in LPS biosynthesis and structure, 2) to identify other H. pylori genes whose expression is increased in response to acidic pH, and 3) to isolate acid-inducible promoters in H. pylori. To accomplish the first objective, analyses will be done to characterize the promoter region and genetic organization of wbcJ and its co-transcribed genes. Transcriptional wbcJ fusions then will be constructed using xylE to examine the expression of wbcJ under different environmental conditions in vitro. The LPS structure of wbcJ mutants will be analyzed to determine the role of this gene in H. pylori LPS biosynthetic pathways. The method of subtractive RNA hybridization will be used to isolate H. pylori genes whose expression is increased during growth at acidic pH. Genes identified by this approach will be cloned and disrupted using insertional mutagenesis, which will permit the study of their role in H. pylori acid survival and colonization. As an alternate strategy to identifying acid-

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regulated genes, we will employ the technique of differential fluorescence induction to enrich for promoters that are up-regulated following exposure to acidic pH, utilizing GFP and a fluorescence-activated cell sorter. The proposed work will further elucidate the mechanisms used by H. pylori to colonize and persist within the gastric environment and will lead to improved understanding of how H. pylori causes disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASPIRIN, HELICOBACTER PYLORI, AND PEPTIC ULCER DISEASE Principal Investigator & Institution: Lew, Edward A.; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: Aspirin and other non-steroidal anti-inflammatory drugs are widely used to treat pain and inflammation, and at low doses, aspirin is also increasingly being used for cardiovascular prophylaxis. However, these drugs have substantial gastrointestinal toxicity and a significant number of patients develop peptic ulcers and GI bleeding. Although infection with Helicobacter pylori is another major risk factor for ulcers, the relationships between aspirin and H. pylori in the development of ulcers remain highly controversial. It is unclear, for example, whether there is an addictive or synergistic interaction between these factors in conferring ulcer risk such that aspirin interacts with H. pylori to increase ulcer complications. Aspirin impairs mucosal protective mechanisms by decreasing prostaglandin production, whereas H. pylori promotes mucosal injury through cytokines and inflammation to form ulcers. Past studies have provided conflicting data on the ulcer risks associated with both factors but they have been limited by recall bias of aspirin use, selection bias, and small sample sizes with short follow-up. The primary goals of the proposed research are to determine the risk of peptic ulcers associated with the joint effects of low dose aspirin and H. pylori infection, the ulcer risk associated with low dose aspirin and a specific virulent strain of H. pylori, known as cagA+ H. pylori, and the risk of GI bleeding associated with low dose aspirin and H. pylori (especially cagA+ H. pylori strains) as compared to those without infection. We will have 80% power to detect a difference of 1.56 in the odds ratio, when comparing the association of aspirin use and ulcer formation in H. pylori positive and negative subjects. As the US population grows older, the chronic use of aspirin for cardiovascular prophylaxis and the subsequent development of ulcers are likely to increase, involving health care costs. The proposed study will provide important information to make an informed decision about aspirin related GI complications and whether H. pylori infected patients are at risk for ulcers and GI bleeding while on aspirin. These results may help identify high-risk patients and lead to strategies that will reduce ulcer complications among aspirin users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTOIMMUNE GASTRITIS INITIATED BY HELICOBACTER INFECTION Principal Investigator & Institution: Lorenz, Robinna G.; Associate Professor; Pathology and Immunology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2002 Summary: (Taken from the Investigator's Abstract) The bacteria, Helicobacter pylori, is a major pathogen which, in addition to infecting over half of the world's population, is linked to gastric and duodenal ulcer disease, mucosal-associated lymphomas, and adenocarcinoma. Infection with H.pylori initially leads to recruitment and activation of

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the non-specific innate immune response. These mononuclear cells secrete proinflammatory cytokines that directly affect the gastric epithelium, as well as recruit lymphocytes into the inflammatory focus. Very little is known about the characteristics of this immune infiltrate, its antigen specificity, or its role in subsequent development of gastric diseases; however, it has now been shown that infection with H.pylori can lead to the production of anti- parietal cell antibodies. This has led to the hypothesis that Helicobacter infection induces an autoimmune response that causes subsequent gastric epithelial cell destruction and pathology. A small animal model of Helicobacter infection, the H.felis mouse model, closely mimics the human disease and allows a careful analysis of the adaptive immune response to Helicobacter infection. The investigator has shown that it is the host T cell response that is crucial for the development of H.felis-associated gastric pathology. This has directed attention to the role of the cellular immune response, and its potential autoimmune nature, in the development of Helicobacter-associated gastric epithelial cell destruction and pathology. This grant application focuses on understanding the relationship between the cellular immune response to Helicobacter infection, and the development of subsequent gastric epithelial alterations. These changes in epithelial proliferation, differentiation, and cell death lead to clinical ulcer disease and increased metaplasia. In order to elucidate this immune/epithelial cell relationship and its sequelae, the investigators propose to identify the immune T lymphocyte subset critical for the development of Helicobacter- associated gastric pathology and to determine the mechanism by which Helicobacter-induced immune responses generate gastric epithelial pathology. The understanding of the basic mechanisms by which the host immune response to Helicobacter induces gastric epithelial pathology will lay the foundation for further studies on the regulation of the inflammatory response and the design of immunotherapies for Helicobacter infection and associated digestive diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BETA2 INTEGRIN SIGNALING IN HUMAN NEUTROPHILS Principal Investigator & Institution: Takami, Mimi S.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-MAY-1999; Project End 31-MAR-2004 Summary: A variety of gastrointestinal disorders, that include H. pylori, NSAID induced gastritis and inflammatory bowel disease, involve the recruitment of leukocytes from the circulation to the site of injury. The severity of the mucosal injury in these disease processes has been directly correlated with the extent of the neutrophil infiltration. In addition, the persistent neutrophil infiltrate which is the hallmark of chronic H. pylori infection, has been implicated as a possible mechanism facilitating malignant transformation in the gastric mucosa. Central to the modulation of adhesion and migration of leukocytes in inflammatory processes such as these, is a subfamily of cell surface receptors, the beta2 integrins. Adhesion through beta2 integrins is a complex process that involves activation of the integrin through an inside out signaling mechanism, triggered by the engagement of well characterized receptors such as the chemokine receptors, IL-8, C5a, and N-Formylmethionlleucyl- phenylalanine (FMLP), cytokine receptors, such as TNF, and activation of Protein Kinase C. Integrin activation results in enhanced binding to ligand, and subsequently, generation of an outside-in signal cascade that may lead to changes in gene expression and cytoskeletal rearrangement, enabling the leukocyte to migrate to sites of injury, and facilitating the physiologic response of the cell. Recent reports have identified Interleukin-8 as an important epithelial-derived inflammatory mediator in both IBD and H. pylori gastritis.

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In neutrophils, I1-8 has been shown to induce chemotaxis, respiratory burst and granule release, and to enhance cellular adhesion. However, the specific effects of IL-8 on beta2 integrin activation and ligand binding have not been closely examined. In addition, while recent reports indicate that IL-8 activates the MAPK pathway through Ras/Rafmediated events, the relationship of these events to beta2 integrin function has yet to be elucidated. Our goal, within this proposal, is to delineate the signal transduction cascades involved in beta2 integrin activation, with a particular focus on the physiologic stimulus at the chemokine receptor. In addition, we will examine post-ligand-binding events, including protein tyrosine phosphorylation and protein-protein interactions that are central to the outside-in signaling cascade initiated by engagement of beta2 integrins on human neutrophils. We will examine the relationship of these events to the complex shape changes involved in aggregation and transmigration. And, as a biological model, we will explore the way in which exposure to Helicobacter pylori, may impact these signals and affect neutrophil adhesion and migration on epithelial surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOSENSOR FOR CONTAMINANT-FREE PLATELETS Principal Investigator & Institution: Elson, Edward C.; Opto-Gene, Inc. 7100 Baltimore Ave, Ste 203 College Park, Md 20740 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-NOV-2002 Summary: Development of a Bacterial Biosensor is proposed to ensure that platelets are sufficiently free of bacteria to be safely transfused into patients. Preliminary results with one prototype demonstrated that rRNA from Helicobacter pylori, a model bacterial pathogen for humans, could be detected by hybridization sandwich assay within two minutes and at 10/4 cells sensitivity. A second prototype with a long-period with alongperiod Bragg grating, which does not require a sandwich assay or signal fluorophore, showed that human IgG could be identified even in a crude bacterial lysate. Both prototypes work with either nucleic acids or proteins, can function as point-of-care devices, and are faster than commercially available tests. Each prototype will be modified and then tested two ways: first, by hybridization with a universal rRNA probe to detect bacterial contamination of platelets. Second, with receptor and/or antibody to detect extracellular release of soluble vascular endothelial growth factor (sVEGF) from platelets when bacteria are present. Each of the four possible configurations will be optimized and compared for sensitivity, specificity, ease of cooperation, potential cost, and other factors. The resulting instrument should prove a powerful and effective tool for rapid and direct determination of platelet safety and for other health related applications. PROPOSED COMMERCIAL APPLICATIONS: The risk of receiving bacterially contaminated platelets may be 50 to 250 times higher than the combined risk per unit of transfusion-related viral infection with HIV-1/2, HCV, HBV, and HTLV-I/II. About four million units of platelets are transfused globally every year. Medicare already adds a $35 premium to each unit of viral-cleansed blood product. By extrapolation, therefore, a minimal cost of $5 per unit to certify platelets as sufficiently free of bacteria would create an estimated $20 million market and would save 100 to 150 lives every year just in the United States alone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOSYNTHESIS OF MEMBRANE GLYCOLIPIDS IN RHIZOBIUM Principal Investigator & Institution: Raetz, Christian R.; Professor & Chairman; Biochemistry; Duke University Durham, Nc 27706

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Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 30-JUN-2004 Summary: Lipopolysaccharides (LPSs) are remarkable glycolipids that comprise the outer surfaces of Gram-negative bacteria, including the symbiotic organism, Rhizobium leguminosarum. In Escherichia coli, the lipid A anchor of LPS is a hexa-acylated disaccharide of glucosamine, bearing phosphate moieties at positions 1 and 4'. The minimal LPS required for a growth of E.coli consists of lipid A and two extra sugars. Emerging genomic sequences indicate that the enzymes that make lipid A in E. coli are present in most other Gram-negative bacteria. Lipid A (often termed endotoxin) is also the active component of LPS responsible for the clinical complications of Gram-negative sepsis. Minor modifications in the structure of lipid A can have profound effects on pathogenesis. Some lipid A analogs are actually potent endotoxin antagonists. Compared to E. coli, the chemical structures of the lipid A and core domains of R. leguminosarum LPS are very unusual. R. leguminosarum lipid A lacks the and 4'phosphates, but is modified with galacturonic acid at position 4'. It is acylated with a peculiar 28 carbon fatty acid, and contains 2-deoxy-2-aminogluconate in place of the proximal glucosamine. The structure of R. leguminosarum LPS indicates the existence of novel enzymes for generating diverse lipid A and core species. It is now established that the first seven enzymes of lipid A biosynthesis are in fact the same in E. coli and R. leguminosarum. The differences arise in the later stages of the pathway. To date, enzymes identified as unique to R. leguminosarum include a 4'-phosphatase that is also a phosphotransferase, a 1-phosphatase, a long chain acyltransferase with its own acyl carrier protein, and three distinct core glycosyltransferases. Characterization of the R. leguminosarum system should provide insights into the function of lipid A-like molecules, including special roles during symbiosis in plants, and affords the opportunity to create novel lipid A hybrids that may have interesting adjuvant or antagonist activities. Some structural features of R. leguminosarum lipid A are seen in human pathogens. Legionella pneumophila lipid A contains a C28 chain, while Porphyromonas gingivalis and Helicobacter pylori lipid A lack the 4' phosphate. In the coming grant period, the specific aims are: I) cloning of the C28 acyltransferase of R. leguminosarum; II) analysis of the lipid A 4'-phosphatase/phosphotransferase, especially its ability to synthesize PtdIns-4-P; III) determination of the enzymatic basis for proximal unit diversity in R. leguminosarum lipid A; and IV) characterization of enzymes that incorporate the unique inner core sugars of R. leguminosarum LPS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BREATH AMMONIA METHOD FOR H. PYLORI DETECTION Principal Investigator & Institution: Putnam, David L.; Pacific Technologies 21806 Ne 1St Redmond, Wa 98053 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-MAY-2004 Summary: (provided by applicant): The project will develop a simple test for noninvasive diagnosis of active Helicobacter pylori infection in the stomach based on measuring ammonia in patients' breath. A novel highly sensitive optical technique will be used to measure breath ammonia, leading to an inexpensive diagnostic procedure that can be conducted in any general practitioner's office. An improved method of detecting gastric H. pylori is of clinical significance because the organism is the cause of most peptic ulcers and is associated with other gastrointestinal diseases including cancers. The new breath ammonia sensing method will be useful for diagnosis of infected patients, as well as for follow-up determinations of infectious status after therapy. Phase I results demonstrated 100 percent agreement with conventional 14Clabeled breath tests The research will optimize the clinical instrumentation, expand the

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scope of the Phase I clinical trial to a larger, more diverse patient set, and study test parameters that maximize the clinical diagnostic value of the test. This work will redisign the sensor and instrument as a logical and practical step to final product commercialization. Subsequent pre-market testing for commercialization will implement those instrument and test procedure and confirm their clinical efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER SERO EPIDEMIOLOGY AMONG THE JAPANESE IN HAWAII Principal Investigator & Institution: Nomura, Abraham M.; Director; Kuakini Medical Center 347 N Kuakini St Honolulu, Hi 96817 Timing: Fiscal Year 2002; Project Start 15-SEP-1983; Project End 30-JUN-2004 Summary: (Adapted from the Investigator's Abstract) This is a sero-epidemiologic prospective study to identify biochemical markers related to common cancers occurring among 11,132 American Japanese subjects examined in Hawaii. Their unthawed serum, obtained many years prior to the diagnosis of cancer, will be used in the investigation. The proposal is focused on five specific cancer sites: prostate, colon, breast, stomach and urinary bladder. Eight specific aims will be addressed: 1) to determine whether low serum isoflavonoid levels increase the risk of prostate cancer; 2) to see if low serum selenium levels increase prostate cancer risk; 3) to determine whether high serum insulin level increases the risk of colon cancer risk in men; 4) to find out if low serum isoflavonoid levels increase breast cancer risk in women; 5) to determine whether men carrying the Helicobacter pylori Vac-A strains are at increased risk for stomach cancer; 6) to see if the presence of H. pylori serum markers increase the risk of total and causespecific mortality in men; 7) to find out if serum levels of vitamin A and carotenoids are inversely associated with urinary bladder cancer risk in men; 8) to determine whether low serum selenium levels increase urinary bladder cancer risk in men. The population base for aim 4 consists of 1787 women, born from 1900 to 1935 who were interviewed and examined from 1975-1977. The subjects for the rest of the aims are 9345 men born from 1896 to 1935, who were interviewed and examined from 1971 to 1976. A wealth of epidemiologic-based data was collected on these participants, and they have been under continuous hospital surveillance for cancer since their examination. Two types of study design will be used in this proposal: 1) prospective study (aim 6); 2) nested case-control study (the rest of the aims). It is estimated that the number of incident cases will be as follows: 376 prostate, 387 colon, 120 breast, 293 stomach, and 131 urinary bladder cancer cases. The number of cause -specific mortality cases should be at least 870 coronary deaths, 1277 cancer deaths and 4145 deaths among the men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOPREVENTION OF GASTRIC DYSPLASIA-LONG TERM FOLLOW UP Principal Investigator & Institution: Fontham, Elizabeth T.; Professor and Chairman; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 08-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): While Helicobacter pylori is now established as a pivotal factor in gastric carcinogenesis, its mechanisms of action and timing in the premalignant process are the subject of research. This project builds upon a recently completed 6-year randomized chemoprevention trial in a high-risk region of Colombia. A significantly greater regression of premalignant lesions was observed in study

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participants who were treated and were cleared of H. pylori infection. Upon completion of the trial, participants who had not been in the anti-H. pylori treatment arm were offered standard triple therapy. Quarterly contact has been maintained with trial participants, and this project now proposes to evaluate the long-term effectiveness of anti-H. pylori treatment in an adult population in which the community prevalence of infection is greater than 90 percent. The specific aims of the study are to: 1. determine the proportion of subjects free of infection in 2002; 2. document the reinfection rates from 2002 to 2007 in subjects free of infection in 2002; 3. compare the H. pylori genotypes in persons receiving treatment and found to be free of infection during the follow-up phase with prior pre-treatment genotypes (1998); 4. determine the status of histopathologic lesions (progression; regression; no change) at the end of the follow-up phase (2006-7) in relation to their infection status over time and previous histopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COORDINATE REGULATION OF BACTERIAL VIRULENCE FACTORS Principal Investigator & Institution: Mekalanos, John J.; Professor; Microbiol & Molecular Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-MAY-1988; Project End 30-APR-2008 Summary: (provided by applicant): For the next funding period of AI-26289, our overall goal is to understanding the biology of five pathogenic microorganisms (Vibrio cholerae, Pseudomonas aeruginosa, Helicobacter pylori, Haemophilus influenzae, and Escherichia coli) in order to discover anti-infective strategies based on the use of small molecule inhibitors. These studies will be horizontally integrated by use of common technologies and genetic approaches. For example, we will use differential fluorescence induction (DFI) to define and study genes expressed in vivo or associated with virulence regulons of biological interest. Genomic microarrays will be used to measure gene expression at the global transcriptional level under various growth conditions, in various defined mutants, and under a series of imposed stresses. These stress challenges will include exposure to host milieu during infection, exposure to host cells, withdrawal of essential gene products through conditional expression, and exposure to toxic compounds, toxic protein aptamers, and inhibitory antibiotics. We will use a variety of methods including the new DNA-chip based "TraSH method" to identify genes required for bacterial growth and viability in vitro and in vivo. We will attempt to identify the function of new essential proteins by characterizing complexes they form with other proteins through micro liquid chromatography tandem mass spectrometry (microLCMS) analysis. Other proteomic projects will include the use of microLCMS to define proteins expressed on the surface of bacteria grown in vitro and in vivo. We will also explore the use of "protein chips" as a means of doing protein-protein interaction analysis and as a new tool for studying host immune responses. Computational methods will be used to mine expression and genomic databases for interesting potential virulence or essential gene products, which will then be analyzed genetically for attenuation in experimental animals. We will use the information we gain on essential processes in pathogenic bacteria to devise sensitive bioscreens that can detect small molecule inhibitors of these processes. Finally, we will screen diverse combinatorial compound libraries in high-throughput formats for "hits" that pharmacologically interfere with essential and virulence related functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--GENETIC CHARACTERIZATION OF H PYLORIA STRAINS Principal Investigator & Institution: Schneider, Barbara A.; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 08-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Helicobacter pylori (H.p.) gastritis is the most common chronic infection worldwide, affecting about half the world's population. In most infected persons, the bacteria produce few ill effects, but in a minority, ulcers and gastric cancer are associated with infection. Factors affecting the severity of results of infection are poorly understood. One factor likely to be important in controlling severity of symptoms is the virulence of the strain of H.p. This core laboratory will perform genotyping of major virulence factors of H.p. strains for the other laboratories of the program project. One key virulence factor is vacA, a secreted cytotoxin, which resembles an ion channel or transport protein. When the toxin binds to gastric epithelial cells, it is taken into the cells in vacuoles (hence the name). Subsequently the cells lyse, and the cell debris contributes to inflammation. The vacA gene contains 2 portions, one coding for a signal peptide, or s portion, and one coding for the middle or m portion. Both s and m are present in multiple alleles (s1a, s1b, s1c, s2, m1, m2a, and m2b), some of which are associated with more severe pathology. In addition, some strains of H.p. produce a cagA protein, which is a marker for a pathogenicity island, a group of 40 genes, which encode proteins, which enhance the virulence of the strain. Another virulence determinant is babA, which encodes an adhesion, which binds the bacteria to the surface of the gastric epithelial cells. This core laboratory will genotype clinical strains of H.p. for cagA, s and m regions of vacA, and babA. The laboratory will culture and genotype clinical strains of H.p. isolated from Colombian and New Orleans patients, and will serve all projects in the application. Genotyping will be performed by the line probe assay (LiPA) and with PCR using radioactive primers. In addition, we have developed and will employ for project 3, a method for performing genotyping from stool samples, which will greatly expand our abilities to genotype strains found in asymptomatic persons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CURE: DIGESTIVE DISEASES RESEARCH CENTER Principal Investigator & Institution: Rozengurt, Juan Enrique.; Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 15-JAN-1990; Project End 30-NOV-2004 Summary: (Taken from the application) The CURE: Digestive Diseases Research Center is composed of a cohesive group of physicians and basic scientists with strong independent grant-supported research programs in the biology of the gut, with special emphasis upon regulation of mucosal cell function and gut neuroscience. CURE first received NIDDK funding in 1974 as a center to study peptic ulcer disease and became a Digestive Disease Core Center in 1989. The research emphasis of the center is acquisition of new knowledge about cellular and physiological processes that control gut function and translation of this knowledge into development of therapy for patients with gastrointestinal diseases. CURE initially established its reputation for work in clinical peptic ulcer disease, physiological regulation of acid secretion, and parietal cell mechanisms for secreting acid. Demonstration that Helicobacter pylori is an essential factor in pathogenesis of ordinary peptic ulcer disease brought new aspects of mucosal cell biology into the forefront of research at CURE. The interests and activities of center members have evolved along with science in this area and now include several facets of

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gastrointestinal regulatory physiology and cell biology. CURE's new name reflects more appropriately the broad interests of its members, including gastroduodenal mucosal physiology and disease; intestinal transport, intestinal inflammation, nutrition, and pancreatic secretion; neurophysiology and neuroenteric disease; and hormones, receptors, and signal transduction. The five Biomedical Research Cores outlined in this proposal provide ready access to technology and to clinical and biological materials that are essential to the programs of center members. These cores provide custom antibody production, sophisticated peptide chemistry techniques, access to modem cellular imaging to study membrane proteins and their functions, animal models for studying physiology and pathophysiology, and access to a broad range of techniques and patients for clinical studies. The Administrative Core provides a wide range of administrative support for members and for center activities including a dynamic enrichment program. The Pilot and Feasibility Program has provided a successful mechanism for aiding development of new research programs by young investigators, and recipients usually have obtained independent funding. The center provides an optimal environment for cooperation and collaboration among its investigators, who have had a major impact on mucosal biology and on peptic ulcer disease over the past two decades and promise to have an even larger impact upon expanded research areas with continued support from the center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINE IMMUNIZATION

RESPONSES

TO

H.

PYLORI

INFECTION,

Principal Investigator & Institution: Ernst, Peter B.; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-MAY-2007 Summary: (provided by applicant): Gastric immune responses interact with bacterial virulence factors to promote the pathogenesis of diseases associated with H. pylori infection. While helper T (Th) cells promote inflammation in response to H. pylori in both humans and mice, they are also essential for immunity in animal models. Effective immunity can be induced by vaccination although antibody responses are not necessary. Since/-/. pylori is a noninvasive pathogen, the "protective" Th cells are believed to modify epithelial cell gone expression such that the niche favoring colonization is disrupted. Th1 cells can augment expression of receptors that bind H. pylori and favor the epithelial damage that ensues. As such, they act as a "pathogenic" T cell. Either endogenous or exogenous ROS can regulate the expression of genes associated with Th1 cells. In contrast, Th2 cells, through the production ofIL-4, IL-5, IL-10, IL-13, IL-25 and TGF-Beta can antagonize the effects of Th1 cells. Tr1 cells, a recently described subset of Th cells, resemble Th2 cells by producing IL-5 and -10 but also produce IFN-gamma similar to Th1 cells. Importantly, Tr1 cells are present in the digestive tract and attenuate the host response to luminal antigen including the induction of colitis in animal models. Cytokines associated with Tr1 cells prevent the generation of ROS, the expression of genes associated with Th1 cells and their effects on bacterial binding and epithelial cell damage. These observations suggest that a "protective" response to vaccines will induce Tr1 cells, or related regulatory Th cells, that are responsible for limiting inflammation. How these cells are derived is unknown and their role in host defense has yet to be defined. This background leads to our general hypothesis that a relative imbalance in helper T cell subsets favors the stimulation of inflammation and epithelial damage in response to persistent infection with H. pylori. More specifically, oxidative stress associated with H. pylori infection selects for "pathogenic" Th1 responses that contribute

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to epithelial damage while a regulatory "protective" Th1 cell will favor tissue integrity and immunity. The overall objective is to define the T cell response to natural infection with H. pylori or immunization and elucidate the mechanisms governing lymphoepithelial cell interactions in disease versus immunity. This will be achieved in the following Specific Aims: 1). Define the factors selecting for "pathogenic" Th cells associated with H. pylori infection. 2). Identify T cell markers that are correlates of immunity. 3). Define mechanisms of host defense attributed to "protective" Th cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION OF H. PYLORI USING ELECTRICAL DNA SENSING Principal Investigator & Institution: Kelley, Shana O.; Chemistry; Boston College 140 Commonwealth Ave Newton, Ma 02467 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): This proposal describes the development of a new class of biosensors exploiting an intrinsic property of DNA: electrical conduction. The capability of dsDNA to conduct electricity, in combination with the ability to measure this conduction in short (<100bp) and specific DNA sequences, will be harnessed to produce sensors with unprecedented sensitivity and portability. Conventional methods of detecting sequences on DNA arrays employ optical detection, and lack the sensitivity required to detect microbial species in clinical samples without extensive processing. The goal of this project is to construct a nanoscale DNA sensor with electrical detection that can sensitively and accurately detect Helicobacter pylori, a bacterium associated with gastric ulcers and cancer, in clinical samples. The specific aims of this project include (1) the demonstration of proof-of-principle for electrical DNA sensing carried out with synthetic DNA molecules modeling a unique H. pylori gene, and (2) the detection of H. pylori in clinical samples using electrical DNA detection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIFFERENTIAL TRANSCRIPTION FACTOR ACTIVATION BY H. PYLOR Principal Investigator & Institution: Smoot, Duane T.; Professor of Medicine; Medicine; Howard University 2400 6Th St Nw Washington, Dc 20059 Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 31-MAR-2007 Summary: (provided by applicant): The discovery of Helicobacter pylori (H. pylori) infection has greatly changed our understanding of upper G.I. tract diseases, including peptic ulcer disease and stomach cancer. The world health organization has classified H. pylori as a group one carcinogen. Reactive oxygen species (ROS) are known carcinogens and have been shown to play a role in gastric cancer. Our studies have shown that H. pylori stimulates the generation of ROS within gastric cells. By placing gastric cells into a pro-oxidant state, H. pylori increases the risk of DNA damage from ROS and the development of cancer. Epithelial cells protect themselves from DNA damage by undergoing apoptosis. H. pylori induce apoptosis is associated with activation of both NF-kappaB and p53. Also H. pylori induced apoptosis is associated with stimulation of the CD95/Fas pathway. Our preliminary studies show that the increase in p53 protein after exposure of gastric cells to H. pylori is associated with increased expression of p14 ARF and down regulation of mdm2. The studies planned in this proposal will identify any interactions between p53 mediated apoptosis and CD95/Fas-mediated apoptosis in response to H. pylori We hypothesize that stimulation of intracellular reactive oxygen species within eukaryotic cells is a major mediator of H. pylori induced cellular injury

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resulting in oxidant associated DNA damage and apoptosis. We further hypothesize that transcription factors p53 and NF-KappaB are important downstream mediators of ROS induced cellular injury from exposure to H. pylori. Our more recent studies show that the rise in p53 after exposure to H. pylori is secondary to stimulation of ARF which stabilizes p53 by preventing Mdm2 inhibition of p53 activity and Mdm2 mediated degradation of p53. Therefore, ROS may be responsible for stimulation of ARF resulting in increased p53. The specific aims of this proposal are: (1) to determine whether or not ROS leads to activation of NF-KappaB which may sensitize gastric cells to apoptosis, dependent or independent of p53; (2) To elucidate mediators of ARF activation by H. pylori leading to increased p53 protein and apoptosis; (3) To determine the involvement of the CD95 (Fas/Apo-1) receptor/ligand system in p53 sensitization of gastric cells to apoptosis induced by H. pylori. Identification of transcription factors activated by this bacterium and elucidation of apoptotic pathways involved will assist us to develop better treatment strategies to prevent serious disease from this infection. By protecting gastric cells from ROS, one may be able to negate the carcinogenic properties of this bacterium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNAK PROTEIN INHIBITOR ANTIMICROBIALS Principal Investigator & Institution: Sturgess, Michael A.; Chaperone Technologies, Inc. 801 Mockingbird Ln Audubon, Pa 19403 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): The activity spectrum and mode of action of native antibacterial peptides represent some of the most exciting subjects of the Millennium, mostly because of the rapid increase of bacteria that become resistant to conventional antibiotics, and the promise of native antibacterial peptides to combat these strains in the clinical setting. Many antibacterial peptides have intracellular target biopolymers, but because the peptides have to reach the cell interior, their action on bacterial and host cell membranes often mask their major mode of action. The best molecules to study these processes are the short, proline-rich antibacterial peptides originally isolated from insects. Pyrrhocoricin, drosocin and perhaps apidaecin appear to inhibit chaperoneassisted protein folding via binding to the multihelical lid region of the 70 kDa heat shock protein DnaK with their amino terminal halves. The carboxy-terminal domains are likely involved in the process of penetration into bacterial and host cells. A designed dimeric pyrrhocoricin analog is currently studied for its ability to protect mice against systemic and local Klebsiella pneumoniae, Escherichia coli, Haemophilus influenzae, Moraxella catarrhalis and Salmonella typhimurium infections. This lead compound cannot kill Staphylococcus aureus, Streptococcus pneumoniae, Helicobacter pylori or Haemophilus ducreyi, among other strains, in vitro. This grant application is concerned with the development of novel peptidic and non-peptidic Hsp70 inhibitors for later development as antibacterial, anti-fungal, anti-parasitic or insecticide agents. In the Phase I stage of this proposal, we will identify the role of each individual amino acid residue in pyrrhocoricin and drosocin in inactivating DnaK and in promoting bacterial or eukaryotic cell entry. These properties will be initially studied on peptides in which each native residue is replaced by alanine or tyrosine. The experiments involving DnaK will include binding studies to the recombinant protein and its synthetic DE helix fragment, the inhibition of the inherent ATPase activity of the protein, and, if inconclusive data are obtained, the inhibition of protein folding as indicated by the alkaline phosphatase and beta-galactosidase activity of E. coli cultures. The ability of the peptide analogs to enter E. coli cells and mouse macrophages will be studied by confocal

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fluorescence microscopy and scanning electron microscopy. In Phase II, we will identify the pyrrhocoricin-interacting residues in E. coli, H. influenzae and Agrobacterium tumefaciens DnaK by using spectroscopic and molecular modeling techniques as well as by fluorescence polarization studies between the peptides and mutated DnaK fragments. When the required structural framework for the two independent peptide functions is identified, a new generation of peptide analogs and peptidomimetic structures will be designed. To this end, the DnaK-interacting residues will be modified to bind to the 70 kDa heat shock protein of currently unresponsive bacterial and fungal strains as well as that of Drosophila modeling obnoxious insects. This line of investigations will include a peptide library with fixed delivery and variable DnaKbinding residues as well as de novo design of Hsp70 inhibitors. Measurements of the in vitro Hsp70-binding and antimicrobial activities will be complemented with a limited set of in vivo efficacy studies. It is our hope that by the end of the grant period we will be able to dissect the native antibacterial peptide sequences to functional domains with amino acid residue accuracy and will provide a new generation of peptide and peptidomimetics lead compounds to fight currently life-threatening infectious diseases and will present a new family of biopesticides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUG RESISTANCE AND GENE TRANSFER IN H PYLORI Principal Investigator & Institution: Berg, Douglas E.; Professor; Molecular Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 30-JUN-2004 Summary: Helicobacter pylori (HP) is a major cause of peptic ulcer disease and an early risk factor for gastric cancer. The two most widely used types of therapies against HP depend on metronidazole (Mtz) or clarithromycin (Cla), in combination with other agents, but resistance (R) to Mtz is common, and CIaR is also known. The resistance mechanisms that predominate in American and European populations have been identified: inactivation of a nitroreductase gene, rdxA (MtzR); and sequence changes in one segment of 23S rRNA. Our analyses of MtzR indicated that Mtz is a prodrug, activated (metabolized) by MtzS HP to hydroxylamine, a mutagen and a bacteriocidal agent. HP is an extremely diverse species, with each isolate readily distinguishable from most others. There are numerous duplicate and divergent genes in the HP genome. We suggest that recombination among these genes, gene transfer among different HP strains, and mutation, can all contribute to bacterial adaptation to different human hosts and in changing gastric environments, and more generally in the evolution of virulence. My long term goal is to understand how HP colonizes its human host, establishes infections that persist for years or decades, and in some cases cause overt disease; how it evolves as a human commensal and pathogen; and how best to combat the infections that it causes. Four sets of experiments are proposed: First, we will seek to better understand the emergence and persistence of drug resistance in HP populations. In these experiments, we will test the idea that mutations resulting in MtzR and/or CIaR diminish bacterial fitness (vigor of growth) in culture and in vivo in mouse infection models. Second, we will examine factors affecting the formation of recombinants in HP, with a special focus on duplicate and divergent genes. This will be modeled using alleles for CIaR, which occur in the 23S rRNA gene; there are two copies of the 23S rRNA gene per HP genome. We will examine transformation of HP to CIaR, and test factors determining if a given HP strain can exhibit a CIaR phenotype while being heterozygous for cIaR and cIaS alleles, vs. if if it must be cIaR/cIaR homozygous. Recombination will also be examined using "synthetic merozygotes", in which a cIaR

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Helicobacter pylori

allele is present in truncated (inactive) 23S rRNA gene in a plasmid vector, along with the duplicate expressed chromosomal 23S rRNA genes. Genetic exchange between different HP strains, and the importance of a mutS-like possible mismatch correction function will also be studied. Third, we will seek to better understand the control of mutation in HP, and test whether Mtz therapy itself is mutagenic. Sensitive genetic tests will be used to assess the mutagenic potency of Mtz in HP in culture and in mouse models. Fourth, we will seek to more fully understand mechanisms of drug resistance in HP. We will assess whether any significant fraction of MtzR and CIaR HP isolates from as yet unstudied human populations (India, China, minorities in the US) acquire resistance by mechanisms that are distinct from rdxA inactivation (MtzR) or 23S rRNA mutation (CIaR), the mechanisms found to underly resistance in the mainstream US population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY AND INCIDENCE OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Corley, Douglas A.; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Although the incidence of esophageal adenocarcinoma is rising more rapidly than that of any other malignancy, little is known about its pathogenesis. In particular, little population-based information is known about its main precursor lesion, Barrett's esophagus. The presence of Barrett's esophagus, a metaplastic esophageal columnar epithelium, effectively identifies persons at risk for esophageal adenocarcinoma. Thus, there is a compelling rationale for characterizing the incidence and major modifiable risk factors for Barrett's esophagus, and how these relate to purported risk factors for esophageal adenocarcinoma. Specific Aims/Methods: A. Evaluate the association between obesity/body fat distribution and Barrett's esophagus using a nested case-control study in the Northern California Kaiser Permanente (NCKP) population. The NCKP population contains approximately 3 million people, and is representative of the gender and ethnic distribution of Northern California. The study would use 313 cases, 313 population-based controls, and 313 controls with gastroesophageal reflux disease (who do not have Barrett's esophagus). We would employ a supplementary dietary questionnaire to evaluate for potential dietary confounders of the obesity-Barrett's esophagus relationship. B. Evaluate the association between serum antibody status for Helicobacter Pylori (including the virulent cagA+ strain) and Barrett's esophagus using a case-control study. C. Assay Barrett's esophagus patients and controls for iron stores and heterozygosity for the C282Y hemochromatosis gene mutation. D. Use the patients identified in these case-control studies to estimate the annual population-based incidence of Barrett's esophagus diagnosis. Obesity and body fat distribution, H.pylori infection, and iron stores represent potentially major, modifiable risk factors for Barrett's esophagus and esophageal adenocarcinoma. Our proposed study will: substantially extend current knowledge regarding the epidemiology of Barrett's esophagus; may partially explain why Barrett's esophagus/esophageal adenocarcinoma occurs predominantly in Caucasian males; estimate the population-based incidence of Barrett's esophagus diagnosis in the United States; and provide information for future intervention trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGICAL STUDIES OF GASTRIC CARCINOMA Principal Investigator & Institution: Correa, Pelayo; Boyd Professor; Pathology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-JUN-1981; Project End 30-JUN-2008 Summary: (provided by applicant): The goal of this Program Project has been and continues to be the multi-disciplinary study of the etiology of gastric cancer. This neoplastic disease is second only to lung cancer in incidence and mortality worldwide. In the United States gastric cancer rates have decreased considerably. There are, however, high-risk groups, especially African Americans, Amerindians, and immigrants from Asia, Northern/Eastern Europe and Latin America. It has become increasingly clear that a major etiologic factor is chronic infection with Helicobacter pylori. About one half of today.s world population is infected, especially groups of lower socioeconomic status. The International Agency for research on Cancer has classified Helicobacter infection as a class 1 carcinogen. There are great differences in the outcome of the infection. Most infections are mild and subclinical. Clinical infections may lead to duodenal ulcer accompanied by non-atrophic gastritis, which does not increase gastric cancer risk, or to multifocal atrophic gastritis, which may lead to gastric ulcer and gastric cancer. Our general hypothesis is that the immune and inflammatory responses determine the outcome of the infection. Our Program Project explores the dynamics of the response with immunologic and histopathologic techniques in adults and children (Project 1,2 and 3). Two epidemiologic projects are also proposed: 1) follow-up of the chemoprevention cohort, which explores the natural history of infection after eradication attempts (Project 1); and 2) study of the dynamics of infection and reinfection in children of a hyper-endemic area in search for answers to the critical events in initiating the possible carcinogenesis pathway, namely persistence of infection in childhood. (Project 3). COLLABORATING INSTITUTION(S): Delft laboratories, The Netherlands Emory University Medical Center Atlanta, GA University del Valle, Cali, Colombia University de Narino, Colombia University de Antioquia, Medellin, Colombia University of Texas School of Public Health, Houston TX APR NOTE: This Program Project Grant has addressed the etiology of gastric cancer for 20 years and is in the fifth cycle of funding. This competitive renewal application continues the unique and multidisciplinary study of gastric cancer. The general hypothesis put forward by this Program Project is that the immune and inflammatory responses determine the outcome of the Helicobacter pylori infection leading to gastric ulcer or gastric cancer. The Program includes 3 Projects and 4 Cores. It was felt at the accelerated review that the investigators had resolved all the problems identified in the last review. The Program Project has continued to build on the broad clinical, pathological, and molecular experience accumulated by the Principal Investigator and his program project staff. Two unique populations of H. pylori-infected individuals located in Colombia are being studied. In one population non-atrophic gastritis (NAG) is more common along with low gastric cancer rates and in the second population multi-focal atrophic gastritis (MAG) is more common with a much higher gastric cancer rate. A major strength of this research and the Program Project is the investigators' matchless understanding of the etiology of gastric cancer in these unique and well-characterized populations. These two populations (a major world-wide resource for studying H. pylori pathogenesis) constitute the major strength of this application along with the more than 18 years of study of this gastric cancer problem by the Principal Investigator in a program project environment. In a previous review there were problems with some of the work not being adequately described for an accurate assessment of its feasibility, but these deficiencies have been eliminated. The program is totally unique, has been highly successful in the past, and should make substantial progress in this new funding period.

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Helicobacter pylori

The recommended merit scores of all three projects was 1.4. Three of the cores, Histopathology, Administrative and Field Activites, and Genetic Characterization are rated superior, and the Administrative and Data Management Core is rated satisfactory. The Program is highly integrated and in a very special way makes the whole more valuable than the parts. This was a unanimous observation by the reviewers. The Program is recommended for 5 years of funding. Project 1, "Chemoprevention of gastric Dysplasia", is led by Elizabeth Fontham, Ph.D. The focus of this project continues to be an important population from Colombia who are at high risk for gastric cancer and who have been the focus of this program project since its inception. A unique cohort of subjects with MAG from this population were the subjects of an interventional study in the 1990's to examine the effect of beta carotene and Vitamin C and/or eradication of H. pylori on the progression of gastric precancerous histological lesions. Contact has been maintained with these subjects, around half of who are now H. pylori-negative. This project will continue to follow these subjects closely by endoscopy and clinical evaluation to determine whether the continuing natural history of progression in gastric preneoplasia is altered by the persistent eradication of H. pylori. A secondary aim will be to determine whether those subjects who become reinfected by H. pylori are infected by less virulent strains, as suggested by preliminary data. The project has many strengths, including its focus on a unique and well-defined clinically relevant population, and the expertise of the clinicians and pathologists, who have proven their ability to work cohesively under the supervision of Drs Correa and Fontham over many years. This project received an average merit rating of 1.4. Project 2. "Immune Response to H. pylori in Non-atrophic Gastritis and Multifocal Gastritis" is led by Augusto Ochoa, M.D. It has continued to improve since the first review. One major exception was the validation of using PBL responses to reflect the immune and inflammatory status of leukocytes in the gastric mucosa. This was addressed satisfactorily in the accelerated peer review. The investigators responded by stating that for the first third of the patients analyzed (numbering 20), in vitro PBL responses will be compared with in situ gastric tissue responses. If concordance is observed, the remaining patients in the study will be followed as initially proposed, with concentration of efforts on PBL analysis. If, on the other hand, concordance between the PBL vs. in situ tissue analysis is not observed, the investigators will be able to adjust their analysis to include both PBL's and in situ analysis of all remaining subjects. This response is entirely appropriate and alleviates the biggest uncertainty in the approach taken in Project 2 during the previous submission. The greatest strengths of this project include the unique patient resources available and the previous productivity of the investigators. The overall goal of defining differences in the host immune response between H. pylori-infected patients at risk of developing gastric cancer versus duodenal ulcers is very worthwhile, and within the capability of the investigators. The project has the potential to help dissect the relative contributions of host and bacteria to the development of gastric cancer. This project received an average merit rating of 1.4. Project 3, "Community Intervention-Follow-up of Colombian Children" is led by Karen Goodman in a consortium arrangement with The University of Texas School of Public Health. This project addresses important questions in an appropriate fashion. In the previous version of this project, a clerical effort resulting in the reviewers not seeing the final draft. This problem has been resolved with many of the perceived scientific problems also being clarified. The 3-drug therapy chosen was identified by the reviewers as "a peculiar combination". In the most recent submission, Metronidazole has been added to create a 4-drug therapy. This regimen is consistent with contemporary medical practices. This project received a merit rating of 1.4 Core A, Histopathology, is led by the Principal Investigator, Dr. Pelayo Correa. This laboratory will perform all the histological and histochemical processing and evaluation of the numerous biopsies taken from each of the projects. It is a critically

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important core for this program project. It will be essential for all three projects, especially Project 1. This laboratory has proven over many years that it is ideally equipped for these purposes, and Dr Correa, the Core director, has an unequalled expertise in the interpretation of gastric pathology. This is a superior core. Core B, "Genetic Characterization of H. pylori Strains" led by Barbara Schneider, Ph.D., provides resources for genotypic characterization of three putative virulence genes in H. pylori strains. The LiPA assay for this purpose is well validated and supported by the experience of its inventor, Dr. van Doorn, who will serve as a consultant. The highthroughput advantages of the LiPA assay will be exploited in Projects 1 and 2. It is not clear whether babA typing will also be done by LiPA or by other, independent PCR's. In addition development of non-invasive genotyping methods using fecal samples is proposed. This core received a superior rating. Core C, "Administrative and Data Management (New Orleans)" is led by Dr. Pelayo Correa, M.D. who is also the Principal Investigator of this grant application. This administrative effort has been quite successful in the past and is very well organized and efficient. This Core had the deficiency during the last review of an underpowered statistical analysis effort. Dr. Correa has addressed this deficiency, and both Ms. Du and Ms. Camargo have been assigned to work under Dr. Mera. The question during the last review was regarding the amount of time Dr. Mera could devote to this Program Project. His credentials are perfectly matched for this Program Project, but his time available was considered inadequate because of the large amount of statistical analysis needed by this Program Project. To satisfy this criticism, two new faculty were recruited the biostatistics area. One of these individuals, Dr. Velasco, is Spanish speaking and could help the program project and reports to Dr. Fontham, the Project Leader of Project 1. Most importantly, the new head of the Cancer Center Statistical Department (just hired the week of the current review at the full professor level) will give 15 percent of his time to this Program. This individual is highly qualified and very experienced with the types of statistical problems that will occur in these studies. Thus, the program project statistical effort is going to be run 25 percent time by Dr. Mera and 15% by the new senior faculty member with 2 capable support people at LSU. This is a strong addition to the Core and resolves the major statistical problem from the last review. This core received a satisfactory rating. Core D, "Administrative and Field Activities (Colombia)" is led by Luis Eduardo Bravo, M.D. As was stated previously this is an outstanding core. The cost effectiveness of this effort is remarkable. Past history of this effort and the intact staff from the previous funding period make this core effort convincing and very workable. Some of the details missing about data flow and quality assurance from the previous review were not entirely provided in this new submission, but the effort is still superior, as the overall coordination between the various units in Colombia and between Colombia and the US look strong. This core received a superior rating. Commentary related to Progress in the current funding period, Integrated Effort, Principal Investigator, Support to be negotiated for replacement and Human Subjects are unchanged from the previous review. REVISION NOTE: Modified to include review panel roster. INDIVIDUAL PROJECTS AND CORES PROJECT 1: Chemoprevention of Gastric Dysplasia: Long-term follow-up of a cohort treatment for H. pylori infection (Elizabeth T.H. Fontham, Dr. Ph.H., 15 percent effort) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF BOTANICALS FOR H.PYLORI INFECTIONS Principal Investigator & Institution: Mahady, Gail B.; Assistant Professor; Prog/Collab Res/Pharmactl Scis; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612

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Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-DEC-2002 Summary: (Applicant's Abstract): After more than a decade of research and controversy, it has been conclusively demonstrated that Helicobacter pylori is the main cause of peptic ulcer disease. High infection rates around the world pose serious health and economic problems. In the U. S. alone, 500,000 new cases, and 4 million recurrences are reported annually, at a cost of $3 to $4 billion dollars. Current therapies for H. pylori infections consist of combinations of antibiotics, and H2 blockers. However, due to the serious adverse reactions, patient compliance is low, leading to the development of antibiotic resistance. Thus, new approaches to the treatment H. pylori infections are urgently needed. For thousand of years traditional systems of medicine have successfully used botanicals (plant-based medicines) for the treatment of dyspepsia, gastritis and peptic ulcers. However, most of these botanicals have not been systematically screened for anti-H. pylori activity. This proposal describes an international, multidisciplinary approach to investigating botanical extracts for the treatment and prevention of H. pylori infections. The work is designed to generate sufficient preliminary data to serve as the basis of more definitive studies. The major goal of the project is to identify and standardize botanical extracts and combinations of extracts for the treatment of H. pylori infections. To accomplish this goal, the project involves (1) selection and procurement of botanicals to be tested (2) extraction of the source materials, (3) short-term in vitro and fn vivo testing biological studies to determine activity and mechanistic information (4) in vivo evaluations to establish safety and efficacy, and (5) determination of the major chemical constituents for standardization of the active extracts. Over the two-year period, approximately 60 new botanicals will be selected and evaluated for antibacterial activity against H. pylori. The list of high priority botanicals for testing will be generated based on data analysis from the Napralertsm database, Medline, German Commission E Monographs and other data sources. The success of this method for plant selection is seen in our preliminary results where an initial testing of 25 identified botanicals led to 13 active extracts. In this project, the botanicals will be procured and extracts prepared. The botanical extracts will be subjected to in vitro bioassay protocols using 15 H. pylori strains. Active extracts will be utilized for in vivo studies. The long-term objectives are to develop safe and effective botanical extracts for the treatment and prevention of H. pylori infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOLDING & MISFOLDING OF PARALLEL BETA-HELIX PROTEINS Principal Investigator & Institution: King, Jonathan A.; Assistant Professor; Biology; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-SEP-1978; Project End 31-AUG-2006 Summary: (provided by applicant): The pathways through which amino acid sequences direct the intracellular folding of polypeptide chains into beta-sheets and beta-helices remain unclear. This limits the ability to extract information from human and other genome sequences. An additional problem in biomedical research and the biotechnology industry is the failure of many protein chains expressed from cloned genes to fold into their native state, instead associating into inclusion bodies. Related protein misfolding and aggregation processes underly a number of human amyloid and protein deposition diseases.A subclass of beta-sheets is the processive parallel beta-helix fold. For the parallel beta-helix P22 tailspike trimer, partially folded intermediates in both in vitro and in vivo folding and inclusion body pathways have been characterized. In the past period of GM17,980, we have resolved additional subunit assembly intermediates, and isolated and characterized three new classes of folding mutants (in

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addition to temperature sensitive folding mutants, and their global suppressors); buried hydrophobic core mutants, triple beta-helix assembly mutants, and cysteine folding mutants. These identity sets of residues directing difterent stages of chain folding and assembly. Using monoclonal antibodies, we identified a role for the ribosome itself in tailspike nascent chain folding within cells. A triple stranded beta-helical region has been shown to act as a molecular clamp in subunit assembly. An algorithm has been developed for efficiently predicting beta-helices, which identifies surface proteins of many human pathogens as beta-helices. Human gamma-D crystallin mutants associated with juvenile onset cataract have been expressed and characterized, giving insight into their molecular pathology. In the next period, we propose to: a) Identify additional hydrophobic stack residues controlling parallel beta-helix folding in both the talispike and monomeric chondroitinase B; b) Identify early in vitro intermediates in the folding of beta-helices; c) Identity sequences which control the formation of the interdigitated triple beta-helix that acts as a molecular clamp; d) Test whether predicted beta-helices of Helicobacter pylori have the beta-helix structure; e) Pursue the unfolding, refolding and aggregation of the all beta-sheet human aamma-D crvstallin, which forms lens cataracts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION POLYPEPTIDE/TFF2

&

REGULATION

OF

SPASMOLYTIC

Principal Investigator & Institution: Wang, Timothy C.; Chief; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Adapted from the Applicant's Abstract): Spasmolytic polypeptide (SP/TFF2) is a member of the trefoil factor family specifically expressed in gastric mucous neck cells, a poorly understood stomach cell lineage that is believed to represent the cell of origin for gastric adenocarcinoma. Previous studies have shown that SP-expressing cells are upregulated at sites of gastric injury, and that SP may play a role in mucosal repair. Work from this laboratory employing a H. felis-mouse model has demonstrated a close relationship between SP-expressing cells and the proliferative precursor lineage, and the investigator has shown that Helicobacter-dependent amplification of the SP-expressing cells is paralleled by a decline in parietal cells, followed later by the development of gastric cancer. This group has generated an SP knockout mouse, and their hypothesis regarding a role for SP in gastric differentiation has been strengthened by preliminary findings in these mice of increased parietal cell number. Transient transfection studies in AGS gastric cancer cells of SP promoter-luciferase constructs have led to the identification of trefoil/growth factor response elements, as well as gastric cell-specific basal enhancers. Taken together, these observations have suggested the hypotheses that: the SP gene represents a marker for proliferating precursor (stem) cells in the gastric mucosa: that it is regulated by trefoil peptides and Helicobacter pylori through a specific cis-acting element: and that SP functions in mucosal regeneration and repair through modulation of gastric epithelial differentiation. They propose to study the function and regulation of SP through the following aims: (1) determine the molecular basis of gastric cell-specific SP gene expression. They will characterize the trefoil response element and cell specific elements in the human and murine SP promoters, and explore possible regulation of SP expression by H. pylori in vitro. (2) Characterize gastric cell-specific promoter elements through in vivo expression in transgenic mice. They will generate mSP-GFP and mSP-beta-Gal transgenic lines and analyze changes in transgene expression in response to Helicobacter in gastric cancer mouse models. (3) Investigate the function of SP utilizing the SP deficient mice generated through targeted

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gene disruption. Changes in gastric differentiation will be quantitated, and the SP deficient mice tested in both NSAID and H. felis models. Overall, these studies will utilize gastric cancer models to explore the function and regulation of SP, and may provide further insight into the biology of mucous neck cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF HELICOBACTER PYLORI VACA TOXIN Principal Investigator & Institution: Torres, Victor J.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-DEC-2003; Project End 30-NOV-2006 Summary: (provided by applicant): Helicobacter pylori infection is a risk factor for duodenal ulcer disease and gastric cancer. One H. pylori virulence factor associated with disease is the vacuolating cytotoxin (VacA). VacA exerts a variety of effects on epithelial cells in vitro, including the formation of intracellular vacuoles and anionselective pores in the plasma membrane. VacA domains involved in assembly of the toxin into oligomeric structures or membrane channels have not been analyzed yet. Also, domains of VacA essential for toxin binding to cells have not yet been analyzed in any detail. The aims of this proposal are: (i) identification of domain(s) required for VacA assembly into oligomeric structures. To accomplish this aim, the yeast-two hybrid method is being used. Preliminary data suggest that the yeast-two hybrid system is suitable for the screening of oligomerization domains within VacA. (ii) mapping the cell binding domain(s) required for VacA binding to target cells. To achieve this aim, a library of VacA carboxyl-terminal deletions has been generated. The mutant recombinant toxins are being expressed in E. coli and tested for their cytotoxic activity as well as their ability to bind to cells. (iii) understanding the mechanism of the dominant-negative phenotype observed with the VacA delta6-27 deletion mutant. To fulfill this aim I am using the VacA recombinant system to determine the minimum amino acid sequence required for the delta6-27-VacA toxin to exhibit a dominantnegative phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GASTRIC PRENEOPLASIA IN H FELIS INFECTED IL10 MICE Principal Investigator & Institution: Berg, Daniel J.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 08-DEC-1997; Project End 30-NOV-2002 Summary: (adapted from the investigator's abstract) The objectives of this proposal are to define the mechanisms by which chronic Helicobacter infection leads to the development of preneoplastic gastric epithelium, using a novel animal model, Helicobacter felis-infected interleukin 10-deficient mice (IL10-/-). Helicobacter pylori infection is the major etiologic agent of peptic ulcer disease, and chronic H. pylori infection can lead to the development of preneoplastic gastric epithelium and gastric cancer. Observations in this application demonstrate that Helicobacter felis infected IL10 deficient mice develop severe chronic inflammation and preneoplastic gastric epithelium. The overall hypothesis of this application is that absence of IL-10 results in the development of a dysregulated immune/inflammatory response to Helicobacter. The chronic, severe inflammation in H. felis-infected IL10-/- mice leads to dysregulated production of growth mediators which alters the normal growth and differentiation of gastric epithelium resulting in the development of preneoplastic gastric epithelium. The

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specific aims of the project are: (1) Characterize the immune and inflammatory response to H. felis in wild-type and IL10-/- mice. The composition of the inflammatory infiltrate in H. felis-infected wild-type and IL10-/- mice will be defined using immunohistochemistry and flow cytometry. The role of immune cell types in H. felis infection will be evaluated using mice deficient in B cells (IL10-/-/Bcell-/-), B and T cells (IL10-/-Rag2-/-), and neutrophil-depleted IL10-/- mice. Cytokine mediators in H. felis-infected IL10-/-mice will be assessed via (a) inhibition of cytokines with neutralizing antibodies; (b) inhibition of prostaglandin production using a cyclooxygenase inhibitor; and (c) the role of NO will be assessed through use of IL10-/NOS-/- mice. (2) Characterize the epithelial phenotype in H. felis infected IL10-/- mice. Northern blot, RNAse protection, and in situ hybridization with lineage specific markers will be used to assess epithelial differentiation in H. felis-infected IL10-/- mice. Proliferation and apoptosis in the development of preneoplastic epithelium will also be assessed. (3) Define the role of candidate growth factors and their receptors in the development of preneoplastic epithelium in H. felis-infected IL10-/- mice. Northern blot analysis, RNAse protection assays, and in situ hybridization techniques will be used to evaluate the level and spatial pattern of growth factor and growth factor receptor expression. Characterization of this model of Helicobacter-induced preneoplasia will enhance our understanding of the mechanism by which chronic H. pylori infection leads to gastric cancer in humans and may lead to new strategies for the prevention of gastric ulcer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION DURING H. PYLORI-HOST INTERACTIONS Principal Investigator & Institution: Solnick, Jay V.; Associate Professor of Medicine; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 01-DEC-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Helicobacter pylori causes an inflammatory infiltrate in gastric mucosa that in about 10% of cases progresses to peptic ulcer disease or gastric cancer. Disease results from an interaction between strain-specific bacterial virulence genes and the particular host response, neither of which is well understood. Since experimental inoculation of rhesus macaques with H. pylori causes gastritis that closely mimics human infection, this model provides a unique opportunity to further our understanding of H. pylori pathogenesis. Rapid progress in genomics and gene expression technologies makes it possible to use the macaque model to study the H. pylori host-pathogen interaction by in vivo analysis of gene expression. We propose to extend our work in the rhesus model of H. pylori into an analysis of bacterial (Specific Aim 1) and host (Specific Aim 2) gene expression during experimental infection. Monkeys will be inoculated with a wild type H. pylori strain that reproducibly infects macaques, or with an isogenic mutant deleted in a specific gene implicated in H. pylori pathogenesis. Since pH is fundamental to host gastric physiology and to the niche in which H. pylori thrives, bacterial and host gene expression will also be examined after pharmacological manipulation of gastric pH. Quantitative real-time RT-PCR will be used to examine expression of H. pylori gene families that are likely involved in H. pylori-related disease or immune evasion. Gene expression in bacterial cells grown in vitro will be compared to that in cells isolated directly from infected monkeys. DNA microarray analysis will be used to study host expression of genes thought to be important in the fundamental processes of inflammation, proliferation, apoptosis, and cell signaling. Since the host immune response is increasingly recognized as a critical

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variable in the outcome of infection, we will also study host gene transcription after immunization with urease coupled with either CpG or alum adjuvant, in order to promote aTh1 or Th2 immune response, respectively (Specific Aim 3). These studies will provide a functional genomic understanding of the H. pylori host-pathogen relationship that may have implications for novel treatment or vaccine strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFECTION

GENETIC

REQUIREMENTS

OF

HELICOBACTER

PYLORI

Principal Investigator & Institution: Salama, Nina R.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Helicobacter pylori (Hp) chronically infect the human stomach of 50% of the population worldwide. Ten to 20% of those infected will eventually present with severe disease including ulcers and gastric cancers. Our working hypothesis is that Hp disease is a by-product of the interaction between bacterial factors necessary for establishing and maintaining infection and the resultant host defenses. Furthermore, this interaction is dynamic with the bacteria modifying the host and the host modifying the bacteria over decades of infection. To study this complex process, we utilize a mouse model of infection which recapitulates many aspects of human disease including a robust immune response that is unable to clear the infection and alteration of gastric gland architecture. Using this model we will characterize the function of known Hp virulence factors in vivo and perform a saturating screen for new Hp virulence genes. Such a screen has not been possible until recently due to lack of experimental tools. In Aim 1 we examine the in vivo role of the major secreted cytotoxin, VacA, which we were the first to demonstrate has a phenotype during mouse infection. In Aim 2 we describe a screen to identify additional Hp virulence genes. Here we take advantage of two tools we recently developed: an Hp transposon mutant library and a novel methodology we call MATT to monitor transposon mutants in a pool using our Hp cDNA microarray. We believe this screen has the potential to gives us a global view of the Hp genetic requirements for establishing and maintaining infection. Finally, in Aim 3 we investigate the PAI, a group of virulence genes that have been recently shown to mediate a number of specific interactions with cultured cells. We describe experiments that address why no in vivo phenotype for this locus has been described to date and new experiments to measure a role for the PAI during mouse infection. Careful study of infection with mutants in vacA, the PAI genes and newly identified virulence factors have the potential to teach us a great deal about wild type infection by revealing process that fail to occur in mutant infections. These processes likely contribute to the various diseases associated with Hp and may highlight potential therapeutic targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC SUSCEPTIBILITY TO INFECTION RELATED CANCER Principal Investigator & Institution: Kato, Ikuko; Pathology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): The long-term goal of the proposed study is to provide a scientific basis to develop efficient primary prevention strategies against infection/inflammation-related cancers. Mounting evidence suggests that a variety of

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infectious agents have a role in the pathogenesis of human cancers. It is estimated that 15.6 percent of the worldwide cancer incidences in 1990 can be attributed to these infectious agents, accounting for a total of 1,450,000 cases. Helicobacter pylori (HP) is ranked top among various infectious agents and represents approximately 5 percent of new cancer cases in the world. These cancers are important from a public health point of view because they are potentially preventable by antibiotics treatment or vaccination. Whereas HP infection is very common (80-90 percent) in populations with high risk for stomach cancer, it is known that only a very small fraction of the population infected with HP actually develops cancer, suggesting a role for genetic components in HPrelated carcinogenesis in addition to that of environmental co-factors. This proposal will specifically focus on the 2 groups of polymorphic genes, receptors to HP lipopolysaccharide (LPS), a cell wall component, which elicits immediate proinflammatory responses, (1) CD14 (C-260T), (2) TRL4 (A896G) and (3) NOD2 (3020insC); and resultant cytokines, (4) IL-8 (T-251A), (5) MCP1 (G-2518A), (6) IL-lbeta (T-31C) and (7) TNF-alpha (G-308A). These polymorphic genes are known to be functional and have been postulated to modify host responses to HP infection. The proposed study will be designed as a spin-off study of a chemo prevention trial for gastric cancer in Venezuela, taking advantage of unique characteristics of the study population, i.e., a strikingly high (95 percent) HP infection rate and high prevalence of gastric premalignant lesions. It will utilize biological specimens and epidemiological and histopathological data collected at the baseline examination from the 2200 participants. Genomic DNA will be isolated from these specimens and tested for the polymorphic genes listed above. The specific aim of the proposed study is to evaluate whether those genotypes or alleles of the polymorphic genes which lead to greater responses to HP infection are associated with increased risk of high-grade gastric precancerous lesions. Secondary aims include to examine histopathological correlates of these polymorphisms and to determine whether selected environmental factors modify the above associations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSEMBLY

GENETICS

AND BIOCHEMISTRY

OF RNA

POLYMERASE

Principal Investigator & Institution: Severinov, Konstantin V.; Associate Professor; None; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: Our long-term goal is to understand the molecular mechanism of transcription and the structure of DNA-dependent RNA polymerase (RNAP)-- the principle enzyme of transcription, and a primary target of regulation. Cellular RNAPs are multifunctional, multisubunit molecular machines. Isolated RNAP subunits do not possess partial biochemical functions of the enzyme (e.g., the ability to melt DNA, or bind NTP substrates). Thus, RNAP functional sites may form by allosteric changes or at subunit interfaces upon assembly of complete enzyme. Understanding inter- and intrasubunit interactions during the enzyme assembly could provide an important key to RNAP structure and the mechanism of transcription. We will continue examining the assembly and structure of RNAP from Escherichia coli (subunit composition alpha2betabeta'), the best understood enzyme of its class, and also the RNAP of the gastric pathogen Helicobacter pylori, which we have recently shown contains a most unusual natural fusion of the two largest subunits (beta-beta ). This will entail: in E. coli-suppressor analysis of conditional RNAP assembly mutants; identification of interacting domains using the yeast two-hybrid system, and biochemical analysis of

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assembly intermediates formed with fragments of RNAP subunits, as well as metal substitution, atomic absorption spectroscopy, localized radical footprinting and fluorescence energy transfer measurements to localize each of the two RNAP zinc ions important for the enzyme assembly; in Helicobacter- DNA sequence analyses of rpoB(beta)-rpoC(beta') gene organization in Helicobacter species other than H. pylori, and in related genera such as Arcobacter; engineering an H. pylori strain with separate rpoB and rpoC genes, tests of this strain for viability and vigor of growth in culture and in appropriate animal models, purification and/or in vitro reconstitution of H. pylori RNAP, and establishment of an in vitro transcription system on defined promoters, and the search for regulatory factors. The results of studies of each RNAP should greatly enrich our studies with the other, and collectively lead to new important insights into eubacterial RNAP assembly, structure, function and biological regulation. Because of strong evolutionary conservation of RNAP, this work is also highly relevant to eukaryotic transcription, where the proposed analyses are not yet feasible. Much of the health relatedness of this project derives from its contribution to the understanding of basic transcription machinery in gastric pathogen H. pylori, and related pathogenic bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GI MUCOSAL BARRIER IN HEALTH AND SURGICAL DISEASE Principal Investigator & Institution: Hagen, Susan J.; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-JAN-1977; Project End 31-JUL-2003 Summary: The major thrust of the proposed work is to identify at cellular level the mechanisms by which surface and other epithelial cells of the stomach and duodenum are injured and are repaired in circumstances commonly encountered in daily life. Simultaneously, factors which affect such injuries, both favorably and adversely, will be evaluated. The circumstances which allow or facilitate recovery of a cell, or those which lead to necrosis or programmed cell death are of special interest. Finally, the process of rapid repair of superficial injuries (restitution) and conditions which influence this restitution of epithelial continuity will be examined in detail. The investigations will be directed toward the following: a) To further understanding of the process of rapid epithelial repair (restitution) with particular reference to the role of intracellular pH, growth factors, and the extracellular matrix. Specifically, the following will be tested: whether activation of the Na+/H+ antiporter is essential for cell migration (restitution) to occur; whether the effect of growth factors to facilitate restitution is mediated by stimulation of the Na+/H+ antiporter; and whether various components of extracellular matrix influence restitution by affecting the Na+/H+ antiporter. b) To define both morphologically and biochemically in gastric mucosal epithelial cells differences between necrotic cell death and programmed cell death. c) To evaluate the reversibility of gastric mucosal epithelial injury of the type encountered in daily living or as a result of an infection such as that caused by Helicobacter pylori and to investigate mechanisms of protection against such injuries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GIS FOR EXTANT DATA: MODELING H.PYLORI AND GI TUMORS Principal Investigator & Institution: Parsonnet, Julie; Associate Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005

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Summary: (provided by applicant): Many large demographic and health datasets exist in the public domain and significant federal resources have been committed to their collection and maintenance. We postulate that, using geographic information systems (GIS) technology, the enormous body of information within these unrelated datasets can be integrated to efficiently explore novel hypotheses. For such purposes, however, precise methods of using GIS have not been well standardized. In this proposal, we intend to develop a method for integrating diverse data sets using GIS and then use the spatial capacities of GIS to answer epidemiologic questions. We will validate these methods using the model of Helicobacter pylori and malignancy. H. pylori is a known cause of stomach cancer, and has been purported to cause colorectal and pancreatic adenocarcinomas and to protect against esophageal adenocarcinoma. The vast array of epidemiologic knowledge on this bacterium and its associated cancers makes it an excellent subject for validation of these methods. We will use GIS to combine data from the U.S. Census, NHANES III, and the SEER cancer registry. We will then assess the spatial correlations between H. pylori infection and specific cancer incidences and mortality rates. Development and validation of this methodology will highlight the utility of GIS in epidemiologic research. It will provide a cost-effective means to harness the power and efficiency of large-scale surveys to address specific hypotheses at low expense, even if they were not considered during the design of the surveys. Application of these methods could potentially allow investigators to use existing data sources to address novel hypotheses that may have otherwise been not feasible to pursue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLOBAL SCANNING FOR RESISTANCE MUTATIONS IN H.PYLORI Principal Investigator & Institution: Weissman, Sherman M.; Sterling Professor of Genetics & Medici; Genetics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Helicobacter pylori (Hp) is a major cause of peptic ulcer disease and an early risk factor for gastric cancer. Metronidazole (Mtz) is an antibacterial agent used against Hp, but resistance is common and is a major reason for treatment failure. Research by D. Berg has shown that this resistance is a polygenic trait and that null mutations in the gene rdxA confers low-level resistance; a mutation in another gene, frxA, results in higher resistance and that higher resistance (hyperresistance) results from mutations in another genes that remain to be identified (Jeong et al. J. Bact. 182:3219, 2000). We [Pan and Weissman PNAS: 99:9346 (2002)] have developed a method for global screening for mutations in complex DNA mixtures. In the present application we propose to optimize and apply this method for analysis of bacterial genomes, and use the method to identify mutations and genes that make Hp hyper-resistant to Mtz. The final purpose of this project is to provide a general research tool for dissecting the molecular mechanisms of bacterial pathogenicity and genome evolution. These experiments will help meet Specific Aim 4 of parent grant AI38166 to DE Berg (co-PI) [To more fully understand mechanisms of drug resistance]. This project is "exploratory" or "developmental," relative to the parent grant, in that we may need to overcome potential "noise" from duplicate and divergent sequences as well as other unexpected problems, and generally optimize this for microbial systems. Nevertheless, this method should allow identification of the genes responsible for hyper-resistance with an efficiency that could not be matched by traditional (e.g. shotgun cloning and DNA transformation) type protocols, especially if different constellations of genes cause hyperR in different strains (genetic backgrounds).

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GNOTOBIOTIC TRANSGENIC MODELS OF THE GASTRIC ECOSYSTEM Principal Investigator & Institution: Gordon, Jeffrey I.; Professor and Head; Molecular Biol & Pharmacology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-DEC-2005 Summary: (Adapted from the Applicant's Abstract): This proposal examines 2 questions. (1) What are the molecular features of gastric epithelial lineage progenitors and how are they affected by parietal cell loss? (2) What role does attachment of Helicobacter pylori to these progenitors play in defining the outcome of H. pylori infection? These investigators have developed a transgenic mouse (toxl 76) where ablation of parietal cells leads to progressive amplification of these progenitors. The progenitors produce NeuAcalpha2,3Galbeta 1,4-glycans that serve as receptors for H. pylori adhesins in vivo. These glycans are also found in human gastric Ca and its precursors. The results suggest that when the relationship between host and H. pylori results in loss of parietal cells, as in chronic atrophic gastritis (CAG), H. pylori tropism to lineage progenitors may occur if there is a matching of H. pylori adhesin and host receptor production. Binding to amplified progenitor cells may then help facilitate initiation and/or progression of tumorigenesis. The investigators will explore this hypothesis using gnotobiotic toxl 76 mice and test its clinical relevance using materials from a completed Swedish case control study of H. pylori-infected patients with Ca + CAG. There are 3 related aims: 1). Obtain a molecular signature of lineage progenitors and of parietal cells. Identify parietal cell factors that affect the progenitors. Lectin panning will be used to recover these cells. Cellular RNA will be probed with Affymetrix GeneChips to identify (i) a panel of molecular markers of these cell types; and (ii) genes expressed in parietal cells that may affect the proliferative status/census of progenitors. The effects of candidates selected from (ii) will be tested directly by gene knockout. 2). Determine the molecular responses of the host when H. pylori interacts with NeuAc-alpha2,3Gal-beta1,4+ progenitors. Germ-free normal and toxl76 mice will be colonized with an H. pylori isolate that produces adhesins that bind to NeuAcalpha2,3Gal-beta1,4+ progenitors. GeneChips will be used to profile host gene expression before and after colonization. The role of mucosal immune cells in the host response will be examined by gene expression profiling of gnotobiotic Ragl-/normal + toxl76 mice. The impact of manipulating expression of the adhesin responsible for progenitor cell attachment will be tested. 3). H. pylori isolates from the case control study will be used to characterize H. pylori genes that affect host responses. Isolates will be tested for their binding to NeuAc-alpha2,3Gal-beta 1,4 glycans. Whole genome genotyping of binding isolates from cases with Ca + CAG, and from controls + CAG will be performed using DNA arrays containing 1661 amplified OREs from the sequenced H. pylori 26695 and J99 strains. Isolates with representative genotypes associated with CAG and Ca will be selected from the panel (or genetically engineered), introduced into toxl76 mice, and host responses defined. These studies should yield new insights about H. pylori pathogenesis plus markers for identifying patients at risk for severe pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H. PYLORI- REGULATORY T CELLS THAT LIMIT HOST RESPONSE Principal Investigator & Institution: Blanchard, Thomas G.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and plays an etiologic role in the development of gastritis and peptic ulcer disease. Infection persists for life despite the induction of histologic gastritis and specific immune responses. Similar observations have been made in the H. pylori-mouse model. However, mice lacking either IL-10 or NADPH oxidase develop inflammation in response to H. pylori that is significantly more intense than infected wild type mice, and spontaneously clear the bacteria from the gastric mucosa. Additionally, eradication of H. pylori from immunized mice following challenge is also accompanied by more intense inflammation. Therefore, H. pylori may persist due to the inability of the host to develop sufficiently intense inflammation during infection. The induction of downregulatory T-cells that prevent aberrant responses to noninvasive bacteria in the colon has been described. These mechanisms may be conserved along the gastrointestinal tract and may be active in the gastric mucosa. This proposal will test the hypothesis that activation of T-cells at the gastric mucosa during H. pylori infection induces IL-10 producing regulatory T cells that suppress the inflammatory response, thus allowing for persistent infection. A correlate of this hypothesis is that vaccination effectively bypasses this down-regulation by activating T-cells in lymphoid tissue where the induction of IL-10 producing T-cells is not favored. We will address this hypothesis by: 1) Characterizing surface markers and cytokine profiles of gastric T cell from infected and immune mice to distinguish regulatory T-cells from protective T-cells. Flow cytometry and ELISA spot assays will be used to examine freshly isolated T-cells. 2) Identify the factors in the gastric mucosa that contribute to the induction of these regulatory cells. Transgenic mice and co-culture models will be used to explore the relationship of specific co-receptors and cytokines to T-cell activation in the stomach. 3) Investigate how regulatory T-cells interact with other cells to down-regulate inflammation. Regulatory T-cells will be studied in mice and in vitro to define the extent of their regulatory properties. These studies will increase our understanding of gastrointestinal immunoregulation and the design of better immunotherapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H.PYLORI ARGINASE MODULATION OF ULCERS AND CANCER Principal Investigator & Institution: Mcgee, David J.; Assistant Professor; Microbiology and Immunology; University of South Alabama Mobile, Al 366880002 Timing: Fiscal Year 2003; Project Start 18-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Helicobacter pylori infects approximately 50% of the human population, causing severe gastric diseases including gastritis, peptic ulcers, and gastric cancer. H. pylori exerts an enormous amount of cellular energy on nitrogen metabolism including the urease enzyme. Therefore, the critical role of urease in virulence has been a major research focus. However, H. pylori has a substantial number of other nitrogen metabolizing proteins, whose role in virulence and maintaining nitrogen balance are poorly understood. Here, the focus is arginase, an enzyme metabolically upstream of urease that converts arginine to urea and ornithine. Polyamines (produced from ornithine) and arginase are elevated in the gastric mucosa of gastric cancer patients. Preliminary data demonstrate arginase is critical for H. pylori survival from acid and nitric oxide (NO), two innate host defenses. Furthermore, gerbils

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infected with wild type H. pylori develop gastritis and ulcers, whereas no pathologies are observed in gerbils infected with the isogenic arginase mutant. The central hypothesis of this proposal is that H. pylori arginase inhibits host NO, elevates polyamines, and contributes to gastritis, ulcers and cancer. To test this hypothesis, there are two specific aims: 1) Determine roles of H. pylori arginase in virulence in tissue culture models and 2) Determine the roles of H. pylori arginase in virulence using gerbils. In aim 1, levels of arginase needed to inhibit macrophage NO and elevate polyamines will be assessed. Arginase-dependent cytokine profiles will be identified. In aim 2 the role of arginase in virulence in the gerbil model will be assessed by determining whether arginase contributes to gastric cancer or ulcer development, induces an immune response, affects host NO, arginase or polyamine levels, and protects gerbils from H. pylori challenge. The proposed experiments will significantly enhance our understanding of the roles of H. pylori arginase in protection from innate defenses as well as roles in ulcer and cancer development and optimization of nitrogen levels in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: H.PYLORI INFECTION IN CHILDREN ON THE US-MEXICO BORDER Principal Investigator & Institution: Goodman, Karen J.; Epidemiology; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant ): The aims of the proposed study are to continue observing the natural history of Helicobacter pylori infection in children of low-income families in El Paso, Texas and Juarez, Mexico who have been followed previously from birth for 12-36 months as part of the Pasitos Cohort Study, which aims to identify factors that influence acquisition and persistence of infection in early childhood. Although it is known that H.pylori infection is associated with factors linked to low socioeconomic status, little evidence to date addresses the influence of environmental factors on the risk of acquiring the infection as opposed to the influence of these factors on the probability of having a persistent infection. The aim of our initial study was to observe the natural history of H.pylori infection during the first three years of life. Evidence suggests that ages 3-6 may be critical in determining whether infection persists throughout childhood into adulthood. Therefore, critical information will be gained from continuing to follow this cohort through six years of age. Specifically, we propose to: extend the original aims of the Pasitos Cohort Study to follow children through six years of age; estimate incidence rates of H.pylori infection in children living on both sides of the Rio Grande in El Paso, Texas and Juarez, Mexico from 3- 6 years of age; estimate rates of elimination of H.pylori infection in children from 3-6 years of age; and estimate the effect of socioeconomic indicators, hygiene, and diet on H.pylori incidence, recurrence, and persistence from 3-6 years of age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: H+ NEUTRALIZATION AND C1- HOMEOSTASIS IN GASTRIC MUCOSA Principal Investigator & Institution: Soybel, David I.; Associate Professor of Surgery; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2003

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Summary: (Adapted from investigator's abstract) This application represents a continuation of the principal investigator's FIRST Award. The long-term goal of this project is to evaluate, at the cellular level, the mechanisms that protect gastric mucosa from the damaging effects of luminal acid. Until recently, it was accepted that a Cl/HCO3- exchanger, located in the basolateral cell membrane, is responsible for regulation of intracellular Cl- levels (aiCl) and intracellular pH (pHi) in surface cells and oxyntic cells. We recently found evidence to suggest that a basolateral Na-K-Cl cotransport process plays a dominant and previously unsuspected role in preserving intracellular Cl- levels of the surface cells and in regulating HCl secretion by oxyntic cells. These findings have altered the previous model and led to the following hypotheses: 1) a basolateral, HCO3--independent, Na-K-Cl cotransporter is the dominant mechanism for regulating aiCl of oxyntic cells and surface cells in Necturus gastric fundus during stimulation of acid secretion; 2) a complementary, Cl-independent mechanism of basolateral HCO3-extrusion is also present in the oxyntic cell and contributes significantly to the "alkaline tide" generated by high rates of acid secretion; 3) expression of basolateral transporters that are dominant in preserving aiCl and pHi in the oxyntic cells is regulated by the gastric neurohumoral milieu; 4) secretory activity of the oxyntic glands plays a major role in regulating cell pH and ion composition of the neighboring surface epithelial cells during high rates of acid secretion and during exposure to ulcerogenic conditions; and 5) the ammonium (NH4+) ion that is produced by the pathogen H. pylori may gain access to the cell via the Na-KCl cotransporter, leading to disturbances in both aiCl and pHi. Studies proposed in this application will address these hypotheses using intracellular microelectrode and fluorescence techniques for measuring pH and ion composition, and molecular methods for evaluating expression of membrane transporters. The specific aims of this application are organized into four parts. First, we will evaluate the relationship of the basolateral Cl--transporting processes and their implications for regulation of HCO3transport and other protective functions in both surface cells and oxyntic cells in the mucosa of the gastric fundus of Necturus. Second, we will examine, in both amphibian and mammalian models, the effects of secretory agonists such as gastrin, histamine, carbachol in stimulating synthesis and expression of the basolateral HCO3- and Cltransport systems in surface cells and oxyntic cells of gastric mucosa. Third, we will evaluate the effects of ulcerogens such as aspirin or indomethacin on activity and expression of basolateral Cl- transport systems in both surface cells and oxyntic cells. Finally, we will explore the interaction between ammonium (NH4+), which is produced by the bacterium Helicobacter pylori, and cell pH and Cl- homeostasis. Using these techniques, we hope to provide detailed information regarding activity and expression of transport processes that preserve ion composition and pH in gastric mucosal cells during acid secretion or exposure to ulcerogenic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEALTH EFFECTS OF ACUTE H PYLORI INFECTION IN CHILDREN Principal Investigator & Institution: Passaro, Douglas J.; Senior Fellow; Epidemiology and Biostatistics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: Helicobacter pylori has emerged as one the world s most common infections and a major cause of morbidity, but little is known about the health impact of acute infection. The PI postulates that the temporary gastric hypoacidity that accompanies acute H.pylori infection increases the risk of diarrheal illness and failure to thrive in

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newly infected children. As initial test of this hypothesis, the PI will analyze previously collected data from a community cohort study of children in Lima, Peru. In order to confirm that gastric hypoacidity is the causal mechanism linking H.pylori infection to diarrheal disease, a novel assay-the quininium resin test--will be adapted and validated for use in children. This test will become a key component of a prospective cohort study designed to demonstrate that acute H.pylori infection leads to concurrent gastric achlorhydria and increased rates of diarrheal disease. This work will increase appreciation of the disease burden mused by H.pylori and could hasten development of an effective vaccine. It should also help to define the clinical syndrome of acute H.pylori infection. Specific aims of this project are: 1. To modify and validate assays for H.pylori infection for use in children, including serum IgG and IgM tests and a stool fecal antigen test. 2. To modify and validate the quininium exchange resin test for gastric hypochlorhydria. 3. To apply these assays in field studies to detect acute H.pylori infection and to determine the prevalence of gastric hypochlorhydria among acutely infected children. 4. To determine whether acute H.pylori infection is accompanied by gastrointestinal symptoms and to determine whether H.pylori infection leads to growth retardation or increases in diarrheal illness. The PI is a clinician and researcher with a career interest in the epidemiology of poorly understood infectious diseases. The PI's Immediate goal is to develop into a independent investigator specializing in translating laboratory diagnostics for use in fieldwork and in characterizing disease mechanisms that underlie the epidemiology of emerging pathogens. The PI's background in international health and epidemiology are ideally suited to conducting the proposed research plan and demonstrate a commitment to academic medicine. The career development plan detailed in this proposal solidifies the PI's prior training experiences while helping him to obtain rigorous training in conducting field trials and in developing expertise in the use of patient-oriented research to adapt diagnostic techniques for widespread use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEAT PATHOGENESIS

SHOCK

PROTEINS

AND

HELICOBACTER

PYLORI

Principal Investigator & Institution: Kurt-Jones, Evelyn A.; Associate Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Helicobacter pylori infection causes gastritis, peptic ulcer disease, gastric atrophy and gastric cancer. The World Health Organization has classified H. pylori as a Class I carcinogen. In animal models, the progression of H. pylori disease from superficial gastritis to gastric cancer is related to the severity of the host inflammatory response. The identification of H. pylori components and host factors that contribute to the inflammatory response may lead to important insights into the mechanism of peptic ulcer disease and/or gastric malignancy. Heat shock proteins are potent activators of inflammatory cytokine production. Heat shock proteins produced by bacteria and endogenous heat shock proteins produced by damaged tissue cell accumulate in foci of infection and inflammation. Our recent data indicate that Toll-like receptors and CD14 are important in the innate immune response to bacterial heat shock proteins. In this proposal we will investigate the role of Toll-like receptors in the recognition of bacterial heat shock proteins and in the control of bacterial infection and inflammation. Specifically, we will use in vitro and in vivo approaches to investigate the

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role of heat shock proteins in H. pylori infection and pathogenesis and development of tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELICOBACTER HOST INTERACTIONS IN ANIMAL MODELS Principal Investigator & Institution: Falkow, Stanley; Professor; Microbiology and Immunology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (provided by applicant): Helicobacter pylori infection is causally associated with gastritis and peptic ulcer, as well as two gastric malignancies, gastric carcinoma and B-cell-mucosa-associated lymphoid tissue (MALT) lymphoma. Our proposed research focuses on the application of genetic and molecular tools to manipulate the H. pylori chromosome and the use of DNA microarray technology to monitor both the host and the pathogen in H. pylori animal models of infection and disease. Specifically, we propose to examine the H. pylori infection of mice and Mongolian gerbil. While none of the cell culture models or the animal models we propose to use can fully reflect what is seen in humans, the mouse model of infection can be used to productively investigate how H. pylori colonizes the stomach. We wish to follow long-term infection of the mouse and the host cell response to long-term H. pylori carriage measured by transcriptional profile changes as compared to uninfected littermates. Also, the mouse infection model is useful to study one form of malignancy caused by H. pylori, MALT lymphoma, and we propose to study this feature of long-term H. pylori murine infection by both bacterial transcription profiling and by the use of a mouse DNA microarray to follow the host response and changes that occur in the malignant transformation. We also propose to identify bacterial genes essential for gastric colonization and persistence in the stomach using a method developed in our laboratory called MicroArray Transposon Tagging (MATT) strategy. H. pylori infection reflects a particularly intriguing example of a host-pathogen interaction. The microbe serves as a tool to understand host cell biology and malignancy. The response of the bacterium to the host cell environment allows us to understand the essence of bacterial pathogenicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HELICOBACTER PYLORI AND GASTROINTESTINAL BIOLOGY Principal Investigator & Institution: Peek, Richard M.; Associate Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Persistent H. pylori infection is a risk factor for atrophic gastritis and distal gastric adenocarcinoma; however, only a small percentage of colonized persons develop neoplasia. Enhanced cancer risk may be related to differences in expression of specific bacterial products, to differences in host response to the bacteria, or to the specific interactions between host and microbe. H. pylori strains that possess the cag pathogenicity island induce more severe gastritis and are associated with an additional risk for developing atrophy and gastric cancer. A specific mechanism by which cagA+ strains may lower the threshold for carcinogenesis is by altering epithelial cell proliferation and apoptosis, processes that can be regulated by host inflammatory mediators such as prostaglandin products of cyclooxygenase-2 (COX-2). Over-expression of COX-2 in vitro inhibits apoptosis, and COX-2 is up-regulated within H. pylori-induced gastritis, atrophic gastritis, and gastric adenocarcinoma specimens. In vitro, H. pylori cagA+ strains stimulate COX-2 expression in gastric epithelial cells.

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Since we and others have shown that cagA+ strains are associated with increased gastric epithelial cell proliferation but attenuated apoptosis in vivo, induction of COX-2 by strain-specific microbial factors may represent a specific mechanism by which certain H. pylori strains heighten the risk for gastric adenocarcinoma. The long-term objective of this proposal is to examine the molecular mechanisms by which H. pylori strains selectively affect COX-2 regulated epithelial cellular turnover in vitro and in vivo. To address this, we will first determine whether H. pylori or secreted bacterial products alter COX-2-dependent apoptosis in a novel in vitro model of bacterial:gastric epithelial cell interaction (conditionally immortalized gastric epithelial cells). COX-2 expression will also be examined in myofibroblasts co-cultured with H. pylori and epithelial cells to more closely approximate events occurring within native gastric mucosa. Second, we will determine whether H. pylori infection affects COX-2-dependent cellular turnover in wild-type and COX-2 deficient mice. Third, we will investigate the role of specific H. pylori determinants on COX-2-regulated cellular responses by inactivating strainspecific genes identified by H. pylori whole genome microarray. H. pylori parental and isogenic mutant strains will then be co-incubated with conditionally immortalized cells and infected into mice. The effects of strain-specific bacterial factors and COX-2 generated products also will be investigated in a murine model of gastric carcinogenesis, INS-GAS hypergastrinemic mice. Systematic studies of each of these variables in vitro and in animal systems that reflect H. pylori pathogenesis in humans should help elucidate their relative importance, direct the course of future intervention and prevention strategies, and potentially provide a model of carcinogenesis arising within the context of chronic mucosal inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELICOBACTER PYLORI LPS SIGNALING AND ROLE IN CHRONICITY Principal Investigator & Institution: Goldberg, Joanna B.; Professor; Microbiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2006 Summary: Helicobacter pylori is a bacterial pathogen that chronically colonizes the human stomach. One of the distinctive features of H. pylori is the lipid A moeity of its lipopolysaccharide (LPS). Compared to the prototypical Enterobacteriaceae lipid A, it has a unique structure and is much reduced in its endotoxic activity. Our hypothesis is that H. pylori LPS has different effects on host cell signaling pathways than Escherichia coli LPS. Further we speculate that these differences result in the inability of the human host to respond and clear the H. pylori infection. We will take a genome-wide approach to detect and analyze changes in the human epithelial cell response to H. pylori LPS. In Specific Aim 1, we will use microarray analysis to detect changes in gene expression in gastric epithelial cells treated with H. pylori LPS compared to untreated cells and those treated with E. coli LPS. Whether these changes are due to the recognition by Toll-like receptor 2 (TLR2) or TLR4 will also be assessed using cells either with transfected TLR2 or TLR4, or with dominant negative versions of these receptors. These findings will be confirmed by RT-PCR. In Specific Aim 2, a proteomic approach will be taken; protein profiles of epithelial cells after H. pylori LPS or E. coli LPS treatment will be compared by 2D gel electrophoresis. Proteins of interest will be identified by mass spectrometric analysis. Together these approaches should allow us to determine the specific program of host responses to H. pylori LPS. This information should give us a better understanding of how this organism is able to chronically persist in the stomach and evade eradication by the host immune system. In Specific Aim 3, we will isolate H.

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pylori strains with alterations in the lipid A structure to determine which portion is responsible for the reduced endotoxic activity. The long-term goal of this research will be to develop a rational approach for new therapeutic treatments for H. pylori infections. Further we anticipate that deciphering the transcriptional and protein profiles resulting from H. pylori LPS will provide us with a framework to recognize the diagnostic features of chronic infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELICOBACTER PYLORI: PATHOGENESIS AND VIRULENCE Principal Investigator & Institution: Simpson, Kenneth W.; Clinical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 18-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) A MCSDA will allow me to pursue advanced training in molecular genetic and cellular biological approaches to bacterial pathogenesis that would complement and markedly extend my current expertise in veterinary gastroenterology and infectious disease. The proposed training program would help me to develop as an independent, nationally competitive, clinical research scientist, capable of contributing importantly to our understanding of Helicobacter pylori infection and the diseases it causes, and more generally to elucidating mechanisms of pathogen-host interactions that are significant in health and disease, for many years to come. The mentor and the outside collaborator that I have chosen are internationally recognized in bacterial pathogenesis and genetics, and molecular cell biology, and have strong records as research mentors. The studies proposed herein aim to clarify the relative importance of host and bacterial factors in determining the clinical consequences of infection with H. pylori. I will test and extending the hypothesis that "the ability of a given H. pylori strain to colonize, invade and damage the gastric mucosa of a given host, and the response that it induces depend strongly on its genotype." The proposed studies utilize a cat-model of H. pylori infection. Cats can become naturally colonized with H. pylori within a few months of birth, have a gastric milieu similar to humans, and develop a mucosal inflammatory response that is more comparable to H. pylori infection in people (e.g. IL-8 upregulation) than widely used rodent models. Aim 1 will identify H. pylori strains of recent human origin that can colonize and induce histopathological changes in cats. Aim 2 will generate derivatives of virulent H. pylori strains of interest with knockout mutations in key virulenceassociated genes, and in particular test the importance in colonization, of the remarkable association of toxigenic alleles of the vacuolating cytotoxin gene (vacA), the cytotoxin associated antigen gene (cagA), and other genes of the cag pathogenicity island (PAI). The related Aim 3 will use those sets of isogenic mutant strains to examine the roles of vacA, cagA and other PAI genes in inducing, or down regulating, pathologies such as gastric mucosal inflammatory and systemic immune responses, hypergastrinemia, and attachment, invasion and damage of mucosal cells. Studies in cats will be correlated with cell and organ culture-based analyses, including induction of IL-8 secretion and the ability to damage, invade and efface. I expect that these studies will provide important insight into bacterial factors that influence H. pylori colonization and pathogenicity. The training proposed herein would allow me to fully develop the skills needed to study bacterial pathogenesis at the cell and molecular levels, and would enable me to pursue a career as a clinical scientist with unique qualifications to explore pathogenic mechanisms at the interface between basic cell biology and clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFICATION OF HELICOBACTER PYLORI VIRULENCE GENES Principal Investigator & Institution: Holland, Michael J.; Professor; Biological Chemistry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from the Applicant's Abstract): H. pylori chronically infects gastric mucosa and is implicated in the pathogenesis of human gastritis, peptic ulcer disease, and gastric cancer. This proposal outlines a functional genomics-based approach designed to identify and characterize H. pylori virulence genes associated with human gastric disease. The proposed experiments will provide a functional map of the H. pylori genome which complements the complete sequences of two fully sequenced H. pylori genomes. A method termed "kinetically monitored reverse transcriptase-initiated PCR"; (kRT-PCR) forms the basis for the experimental plan. This method was developed in the laboratory of the principal investigator, and permits high throughput transcript quantitation. Genome-wide transcript profiling is proposed for H. pylori in certain benchmark states. The effects of growth phase, pH shift, iron, and human epithelial cells on H. pylori gene expression will be analyzed. These growth conditions, as well as knockout mutations within the cag pathogenicity island and within specific transcription factor genes, will be tested for their effects on the H. pylori transcriptome. Candidate virulence genes identified from the genome sequence include those involved in molecular mimicry, LPS biosynthesis, outer membrane proteins, candidate "phase variation" genes, and several hundred H. pylori-specific genes identified by comparisons of H. pylori genome sequences with those of other pathogenic and nonpathogenic bacteria. The H. pylori transcriptome will be organized into operons. Operon structures and coordinate expression profiles should reveal potential functions for unknown ORFs. Gene expression profiles for H. pylori in vivo will be obtained using a non-human primate model. Transcript profiles obtained under a variety of in vitro conditions will be organized into relational data sets and analyzed to reveal transcriptional paths and networks operative in H. pylori. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE RESPONSE TO H PYLORI GASTRITIS Principal Investigator & Institution: Ochoa, Augusto C.; Associate Professor; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 08-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Helicobacter pylori (H. pylori) infects over half of the world's population and is associated with multiple disease states ranging from gastritis and duodenal ulcer to gastric cancer and lymphomas. The mechanisms leading from infection to malignancy are not clearly established, but are prominently associated with the type of inflammatory response to the bacteria. In addition to inducing an antibody response, H. pylori causes a T cell response which initially appears to be a Th1 type with the production of IL2, IFNgamma, and TNFalpha and the development of gastritis. The type of gastritis has been divided into two major categories by its histologic appearance, non-atrophic gastritis (NAG), generally associated with duodenal ulcer disease, and Multi-focal atrophic gastritis (MAG), associated with gastric ulcers, epithelial dysplasia and gastric cancer. Most of the previous work has studied the immune response on patients with NAG, while little is known on patients with MAG. Our preliminary data comparing both groups of patients shows an increased infiltration by B cells and an enhanced expression of HLA-DR expression in patients with NAG, which markedly decreases in patients with MAG. In contrast the peripheral blood

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lymphocytes of patients with MAG show a significantly increased production of IFNgamma, IL5 and IL10 after stimulation with H. pylori antigens. However, our data also shows that H. pylori can impair the T cell response by diminishing the proliferation to mitogens, altering the expression of signal transduction proteins and, in patients with MAG, increasing the production of arginase, an enzyme known to diminish the T cell response. Therefore our hypothesis is that the immune response to H. pylori antigens differs in patients with NAG and MAG and therefore plays a central role in determining the type of gastritis developed by the host and its possible progression to gastric malignancy. To test this hypothesis we have developed the following specific aims: 1. To Compare the local inflammatory response in the gastric mucosa of patients with Nonatrophic antral gastritis (NAG) and patients with Multi-focal atrophic gastritis (MAG) using histopathology, immunohistochemistry and in situ hybridization techniques. 2. To compare the cellular immune response of peripheral blood lymphocytes and gastric mucosa lymphocytes to H. pylori antigens in patients with NAG and MAG. 3. To identify the mechanisms by which H. pylori impairs T cell signal transduction and T cell function in patients with H. pylori induced gastritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE RESPONSE TO HELICOBACTER PYLORI VACA AS A MARKER Principal Investigator & Institution: Perez-Perez, Guillermo I.; Associate Professor of Medicine and Micr; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 06-AUG-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Although gastric cancer mortality rates are gradually decreasing around the world, there are countries, especially in East Asia in which this disease remains prevalent. Helicobacter pylori colonization has been strongly associated with gastric cancer in cohort and case-control studies. Until now, most studies have reported an association between H. pylori and gastric cancer using serological surveys with pools of cell surface preparations from the bacteria as the antigen. However, H. pylori isolates from different geographic areas vary in genotype. We propose to design specific antigenic regions from the major virulence marker of H. pylori (VacA), and by assessing the immune response to this bacterial antigen, determine whether it is a better predictor for the risk of development of gastric cancer in selected populations. For VacA we will obtain peptide antigens specific for the mid region (m1 and m2) because preliminary data suggests that differences in this region may be a predictor of the development of gastric cancer. From a nested case-control study of Japanese-Americans in Hawaii, serum samples were obtained from individuals before they developed gastric cancer over a 21-year follow-up. We also have serum samples from control individuals who did not develop gastric cancer. We expect to find that the immune response to one particular vacA genotype (m1) is predominantly observed in those patients who developed gastric cancer compared to those in whom gastric cancer did not develop. If our hypothesis is correct, we hope to establish a simple and economical serological test to assess the risk of gastric cancer development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOBIOLOGY AND PREVENTION OF H PYLORI DISEASE Principal Investigator & Institution: Smith, Phillip D.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294

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Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: Worldwide, the most common bacterial pathogen of the gastrointestinal tract among humans is Helicobacter pylori. Chronic infection with this noninvasive organism is the leading cause of gastritis, gastroduodenal ulcer and gastric carcinoma. In the U.S., the cohort prevalence of H. pylori increases approximately 10 percent per decade, whereas in developing countries, such as Chile, up to 80 percent of school-age children are already infected. Prolonged infection and its attendent inflammation predispose the gastric mucosa to malignant transformation, causing gastric cancer to be the leading cause of death in many developing countries. Since therapeutic eradication of H. pylori is expensive and unlikely in many countries, an effective vaccine is highly desirable, but its development will require elucidation of the mechanism(s) by which H. pylori causes mucosal inflammation. Accordingly, we hypothesize that: 1) After colonization of gastric mucosa, H. pylori releases antigens that are absorbed Into the lamina propria where they stimulate T helper type 1 (Th1) mucosal lymphocytes to produce cytokines that promote a cellular inflammatory response. 2) H. pylori antigens, such as urease, can be delivered in novel vaccines to induce protection against infection. 3) Along with the antigen, regulatory cytokines can be delivered in the vaccine to direct the local response from a Th1 inflammatory response to a Th2 humoral response. These hypotheses will be tested with the following four specific aims: 1) Determine whether human H. pylori gastritis in geographically diverse populations is associated predominantly with Th1 CD4+ lymphocytes, which promote a delayed hypersensitivity response, or with Th2 CD4+ lymphocytes, which promote a humoral B cell response. 2) Determine which H. pylori products stimulate purified primary mucosal cells to produce the cytokines associated with H. pylori gastritis (Specific Aim 1). 3) Characterize the cytokine response in mice infected with H. pylori in order to identify the dominant antigens that induce gastric inflammation and the Th cytokines (Specific Aim 2). 4) Using two new vaccine strategies readily adaptable to the human, determine whether oral vaccination with the dominant H. Pylori antigen(s) (Specific Aim 3) and immunoregulatory cytokines (Specific Aims 1 and 2) protect mice against challenge infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOLOGICAL MALIGNANCIES

BASIS

FOR

H.

PYLORI-RELATED

Principal Investigator & Institution: Obonyo, Marygorret; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The overall goal of this award is to provide a mentored research environment so that the candidate can develop into an independent investigator in the field of gastric cancer induced by Helicobacter pylori infection. The candidate is currently receiving postdoctoral training support under an NIH Research Supplement for Underrepresented Minorities, working on the inflammatory response to H. pylori infection of the gastric mucosa. This award will allow the candidate to develop a related but independent project on the role of the immune response to H. pylori in the development of gastric cancer. The candidate has received extensive training in animal models of infection and the molecular analysis of inflammatory mediators. The immediate career goal is to initiate the proposed work that builds on previous training and expertise but that moves in a new direction relevant to gastric cancer. The long-term career goal is to obtain independent funding for this project and to secure a faculty-level academic appointment. These goals will be achieved by mentoring from two senior

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investigators with extensive experience in research training and in the proposed area of study. Career development will be enhanced by a close but progressively independent scientific relationship with the mentors. The full resources of the UCSD Cancer Center will be used by the candidate. Increasing independence will be achieved by presentations at scientific meetings, critical reviews, publication of work, and grant submissions in later years. The research project is formulated to develop an independent line of investigation that is based on the previous and current work of the candidate. H. pylori infects the gastric mucosa, leading to peptic ulcers and a high risk of gastric cancer. The central hypothesis of this proposal is that H. pylori-induced immune response dysregulates gastric epithelial cell turnover, resulting in carcinogenesis. The candidate has developed mouse and cell culture models of H. pylori infection and will use these to determine the roles of inflammatory mediators in gastric epithelial cell apoptosis and in the regulation of cell proliferation. Under this award, the candidate will be able to develop this work into a productive project that will gain independent funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPAIRED TUMOR IMMUNITY DURING H PYLORI INFECTION Principal Investigator & Institution: Reyes, Victor E.; Professor; Pediatrics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-JUN-1995; Project End 31-MAY-2004 Summary: Helicobacter pylori is an important pathogen which plays the major role in chronic gastritis, gastric and duodenal ulcers and gastric carcinomas. Although H pylori infection of the gastric epithelium elicits immune responses, insight into the mechanisms that regulate the development of those responses is limited. Recent studies have suggested that mucosal epithelial cells are active participants in immune responses to mucosal pathogens. The antral gastric epithelium constitutively expresses class II MHC molecules, and our cells have shown that these epithelial cells express other important markers which are required by antigen presenting cells. We noted that gastric epithelial cells in vitro and in vivo expressed the CD86 co-stimulatory molecule and this expression increased in parallel with the rise of local CD4+ T cell numbers and epithelial class II MHC expression increased in parallel with the rise of local CD4+ T cell numbers and epithelial c;ass II MHC expression during infection with H. pylori. Our most recent studies suggest that H pylori antigens are endocytosed by gastric epithelial cells and transported into endosomes that contain HLA-DM, a molecule which is essential in class II MHC-mediated antigen presentation and immunity to pathogens. Thus, gastric epithelial cells possess key functional elements of antigen presenting cells. Since antigen processing and presentation are pivotal events in the development of an immune response, our observations have led us to hypothesize that gastric epithelial cells are central regulators of the inflammatory and immunologic responses during H. pylori infection and that the nature of those responses is influenced by the bacteria. To examine this hypothesis we will address the following specific aims, as natural extensions of the studies performed during the initial period of funding. 1) Characterize the mechanisms of antigen internalization by gastric epithelial cells. In this aim we will (a) characterize the H. pylori antigens that are selectively internalized by human gastric epithelial cells and the mechanisms that promote their uptake; (b) define how internalized H. pylori antigens may alter various steps in the normal antigen processing (steps) and (c) identify the H. pylori peptides that are selective for presentation to T cells by gastric epithelial cells. 2) Characterize the mechanisms that allow gastric epithelial cells to influence CD4+ T cell function. In this aim we will (a) define the distribution of class II

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MHC in polarized gastric epithelial cells and (b) characterize the expression and function of Ii-CS, an essential co- receptor for CD44 on T cells, by human gastric epithelial cells. The overall goal of these studies is to better understand the interactions between H. pylori, the gastric epithelium and immune cells that determine the outcome of the infection. The studies may help explain why H. pylori infection persists and whether mechanisms that allow H. pylori to evade immune defenses may also permit the associated neoplasms to evade immune surveillance. Understanding the molecular basis for the regulation of the local immune response to natural infection will also facilitate the development of therapeutic or prophylactic vaccines against this clinically important pathogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VIVO PATHOGENESIS OF HELICOBACTER PYLORI Principal Investigator & Institution: Fox, James G.; Director and Professor; Div of Comparative Medicine; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): H. pylon, an infection approaching 100 percent in developing countries, has been strongly linked epidemiologically to gastric cancer, but the mechanism and cofactors required for gastric cancer are poorly understood. Furthermore, it is not known at what stage in progression to gastric cancer that eradication of H. pylon would interrupt the carcinogenic process. Polyparasitism is also ubiquitous in developing populations where H. pylori is endemic. The investigators have developed a C57BL/6 mouse model of chronic H. pylori/felis gastritis that is characterized by the progressive development of gastric atrophy, intestinal metaplasia and invasive gastric cancer. The mechanism of lesion development appears to involve increased apoptosis, mucus neck proliferation, intestinal metaplasia leading to altered cellular differentiation and changes in mucin phenotype and progression of invasive cancer in submucosal vasculature. They have also investigated bacterial and environmental factors that influence disease pathogenesis by generating isogenic mutants lacking specific candidate virulence determinants and by maintaining Helicobacter infected animals on diets high in salt. They have recently shown that in mice coinfected with helicobacter and a helminth infection, H. polygyrus, the gastric cytokine Thl/Th2 profile switches and the gastric phenotype changes from a Thl to a Th2 type gastritis. They now propose to explore the effects of specific genetic alterations, environmental influences and coinfections on the mucosal response and progression of Helicobacter associated gastric lesions. Specifically, they will ask whether 1) progression of H. pylon gastritis can be interrupted at critical points in the disease by antimicrobials or therapeutic vaccination to prevent development of premalignant lesions and gastric adenocarcinoma in the gerbil and/or mouse model 2) Alternatively, do environmental factors such as dietary salt, accelerate or otherwise alter the carcinogenic process, and importantly does the strain of H. pylon (with and without specified pathogenic determinants) influence the outcome of gastric disease in the mouse and gerbil model 3) Does modulation of the Thl/Th2 axis of the immune system by various helminth infections influence the severity and progression of gastritis in rodent models. Overall, these rodent models of Helicobacter infection will be used to study the mechanism by which Helicobacter contributes to neoplasia, and the factors (host, bacteria, dietary or co-infections) which confer susceptibility and/or resistance to premalignant lesions and gastric cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFECTION AND CARDIOVASCULAR DISEASE Principal Investigator & Institution: Davidson, Michael; Medstar Research Institute Hyattsville, Md 20783 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 30-JUN-2004 Summary: Recent studies have associated evidence of Chlamydia pneumoniae infection with coronary and carotid atherosclerosis and evidence of increased infection with cytomegalovirus (CMV) in patients developing restenosis or with atherosclerosis. Several other common pathogens have been less consistently associated with atherosclerosis. Altered parameters of inflammation and hemostasis have been identified as prognostic factors of myocardial infarction and have been linked as possible pathogenetic mechanisms. Recent studies have indicated that peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease frequently called Chlamydia pneumoniae DNA and stimulation of PBMCs can reflect an unsuccessful host cellular immune response to CMV associated with elevated C-reactive protein (CRP). This proposed study is both a nested case-cohort study and a nested cohort analysis within the Strong Heart Study (SHS), an ongoing cohort study of 4,549 American Indians. This study will utilize previously collected specimens, baseline data, and the planned ultrasound measurement of carotid wall thickness (IMT) in SHS participants. Within the initial SHS cohort, 400 definite cases of incident myocardial infarction, coronary heart disease, and stroke will be compare with 400 control individuals with no such diagnoses and matched for age, gender, and residence. Their prior serum specimens will be analyzes for Chlamydia pneumoniae-specific IgG, IgM antibody, for cytomegalovirus-specific IgG antibody, and for CRP. In addition, assays will be performed for antibodies to Helicobacter pylori, hepatitis A virus, (HAV) and herpes simplex virus (HSV) type 1 and 2. Correlations will be made with baseline parameters of lipids, coagulation, and adjusted for potential confounding variables of tobacco use, pneumonia, and altered pulmonary function. An additional analysis of a subcohort, the above 400 controls, will be performed looking at the outcome of their carotid IMT, a parameter of subclinical atherosclerosis, in relation to serologic results indicating a prior exposure to CMV, Chlamydia pneumoniae, and/or other pathogens approximately 8 years preceding ultrasound testing. Both case-control and cohort analysis will be stratified by levels of hemostasis and inflammation, including CRP, fibrinogen, Lp(a), and plasminogen- activator inhibitor-1. A separate nested substudy performed on PBMCs, prospectively collected from 80 cases and 80 controls, will examine the host T-cell proliferative response to CMV and other pathogens in relation to disease and also search for a chronic persistent infection with Chlamydia pneumoniae evidence by DNA detection. Thus, this study will assemble a prognostic profile of infectious, inflammatory, and hemostatic factors and provide a foundation for possible future primary prevention trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERACTION OF HELICOBACTER PYLORI WITH PHAGOCYTES Principal Investigator & Institution: Allen, Lee-Ann H.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 30-JUN-2004 Summary: Description (Adapted from the applicant's abstract): Helicobacter pylori is a gram negative bacterium which colonizes the gastric epithelium of up to half of the world's population and plays a causative role in the development of gastric and duodenal ulcers and gastric adenocarcinoma. One of the hallmarks of H. pylori is its

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persistence, and bacteria are not cleared by the host immune system. This may be explained in part by the fact that H. pylori is readily phagocytosed by macrophages, but the internalized bacteria are not killed. Significantly, preliminary data obtained by the PI suggest the following hypothesis; H. Pylori survives for at least 20 hours inside macrophages by disrupting phagosome maturation. Moreover, this appears to occur by a novel mechanism that involves 1) delayed phagocytosis 2) homotypic fusion of early phagosomes and 3) bacteria-stimulated secretion of lysosomal enzymes from infected cells. The long-term objective of this study is to dissect the mechanism of H. pylori survival in macrophages at the molecular level and to identify the host and bacterial factors required for this process. Specifically, the PI will characterize the H. pylori phagosome in macrophages and use immunofluorescence and confocal microscopy to quantify phagosome pH; electron microscopy to determine phagosome structure; and video imaging of live cells to determine whether H. pylori phagosomes interact with the endosomal compartment. Subcellular fractionation and Western blotting, and immunoelectron microscopy, and antisense oligonucleotides will be used to define the roles of phosphatidylinositol 3-kinase, protein kinase C-zeta, and rab5 in phagocytosis of H. pylori. In addition, whether macrophage-activating cytokines and/or serum opsonins increase phagocytic killing of H. pylori will be determined. Finally, H. pylori mutants with known mutations in urease and VacA will be used to assess whether these bacterial factors are essential for bacterial survival inside macrophages. These data may be the first indication that H. pylori can disrupt phagosome maturation in macrophages. A complete dissection of this process at the molecular level may lead to novel therapies for treatment of H. pylori infection and reduce the significant morbidity associated with ulcer disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATHEMATICAL COLONIZATION

MODELS

OF

H

PYLORI

GASTRIC

Principal Investigator & Institution: Blaser, Martin J.; Dir, Division of Infectious Diseases; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the Applicant's Abstract): Helicobacter pylori, a gram negative bacteria that colonize the human stomach, are associated with diseases of the upper gastrointestinal tract. Examination of the selective pressures on H.pylori provide a model for host interactions with resident flora since (I) H.pylori strains are highly diverse, and continued variation is occurring during colonization of a single host; (ii) H.pylori strains lack SOS repair, are naturally competent, and have substantial ability to exchange DNA with other H.pylori cells, providing opportunities for the observed "quasi-species" development; (iii) H.pylori Lewis expression varies during colonization and host characteristics selected for particular phenotypes; (iv) molecular loci have been identified that are involved in Lewis variation, and mouse models have been developed in which variation can be predictably observed; (v) Mathematical models have been developed for H.pylori colonization in general and the dynamics of Lewis expression can be measured and develop a model to predict its behavior. The specific aims are (1) To construct an experimental rodent model for assessing population genetic changes in H.pylori during gastric colonization of a single host, and to develop a deterministic mathematical model that is representative and predictive. (2) To assess the effects on variation of prior host phenotype, inoculum size, bacterial mutation rate, and host immunological response on H.pylori population dynamics, phenotypes, and genotypes

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to better identify the parameters of the mathematical model. (3) To examine the effect of recombination between two different H.pylori strains during experimental infections, and to develop representative mathematical models for this more complex phenomenon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF GROWTH INHIBITION BY HELICOBACTER PYLORI Principal Investigator & Institution: Ashktorab, Hassan; Associate Professor; Medicine; Howard University 2400 6Th St Nw Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The discovery that H. pylori is an important factor in the development of peptic ulcers has dramatically changed the way ulcer patients are treated. Ulcers heal faster in persons treated with antibiotics in addition to acid medication. One possible explanation for this observation is that cell generation is impaired by H. pylori; thus, ulcer healing occurs more rapidly in the absence of H. pylori infection. Epidemiological studies have strongly associated H. pylori with gastric carcinogenesis. These data led the World Health Organization to designate H. pylori a Class I carcinogen. It is felt that at least half of all gastric cancers are attributed to infection with this bacterium. However, there is little known as to how H. pylori may directly effect gastric cells to cause gastric cancer. Epidemiological data supports this bacterium as a cofactor because it causes chronic gastritis which may progress to atrophic gastritis, a precursor lesion for intestinal type gastric cancer. However, this bacterium is also strongly linked to diffuse gastric cancer which occurs in otherwise normal (non-atrophic) gastric mucosa, where the bacterial infection is present at the time the cancer occurs. In vivo studies show that some bacterial strains cause significant cell injury in the absence of a rise in gastric apoptosis. One explanation is that the bacterium, while causing cell injury, is able to down regulate apoptosis. The decrease in apoptosis in injured gastric cells is one possible mechanism by which this bacterium might directly increase the susceptibility of gastric cells to carcinogenic conversion. This grant proposes to evaluate the direct effects of H. pylori on the cell death in gastric epithelial cells. The Specific Aims of this project are: 1)To better elucidate the involvement of the p53 pathway in H. pylori induced apoptosis by determining the extent of phosphorylation of p53 in cells exposed to H. pylori strains and the importance of phosphorylation at serine-15,-20 and-46 in regard to apoptosis. Also, to evaluate p53 phosphorylation in response to ROS species in the absence of H. pylori and in the presence of H. pylori and antioxidants. 2)To determine the involvement and significance of activation of p53AIPl, which is activated by phosphorylating p53 at serine-46. The mechnism of bacterial exposure on the gastric epithelial cell death has not been studied in regard to p53. These studies are important to elucidate specific p53 pathways that are modulated by exposure to this bacterium, resulting in an regulating cell death. Specifically, whether or not stimulation of reactive oxygen species (ROS) by H. pylori is essential for p53 phosphorylation leading to apoptosis. These studies will help to establish how bacteria can increase apoptosis possibly through generation of ROS and in specific circumstances this may alter one's risk of developing cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REDUCTASE

MECHANISTIC

STUDIES

OF

ALKYL

HYDROPEROXIDE

Principal Investigator & Institution: Poole, Leslie B.; Associate Professor of Biochemistry; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-DEC-1993; Project End 31-DEC-2005 Summary: The bacterial alkyl hydroperoxide reductase system serves to protect against the toxic and mutagenic effects of oxidative stress. AhpC, the cysteine-based peroxidase component, is a member of the ubiquitous "peroxiredoxin" (Prx) family and reduces H2O2 and organic hydroperoxides through transient generation of a cysteine sulfenic acid on the enzyme and subsequent intersubunit disulfide bond formation. AhpF, the flavin-containing reductase component, is present in most, but not all, bacteria and efficiently transfers electrons from NADH (or NADPH) to AhpC. Mammalian Prxs have been implicated in such diverse processes as cellular proliferation and differentiation, immune responses and cell signaling. While most AhpC/Prx homologues are highly expressed and play an important role in oxidative defense, only the AhpC from Helicobacter pylori (the causative agent of gastric ulcers linked to stomach cancer) is known to be absolutely required for viability of that organism. The first specific aim of the proposal focuses on (1) the conformational states, oligomerization and membrane association thought to change during turnover of Salmonella typhimurium AhpC and mammalian Prx II in the presence of peroxides, and (2) the participation of a putative general base catalyst (Arg119) in peroxide reduction by AhpC. The second specific aim explores the mechanism of electron transfers to and from the N-terminal disulfide center of S. typhimurium AhpF. This center (Cys129- Cys132) is part of a distinct redox domain in AhpF known from our studies to mediate electron transfer from redox centers (FAD and Cys345-Cys348) in the C-terminal portion of the protein to AhpC. Our recent crystallographic analyses of AhpF have demonstrated a unique architecture for the Nterminal domain (NTD) and a poorly- characterized homologue, protein disulfide oxidoreductase (PDO), from a thermophile; both NTD and PDO are composed of two intimately-associated thioredoxin-like folds with a putative active site glutamate from the first half acting as a general acid-base catalyst for chemistry at the Cys-X-X-Cys motif of the second half of the domain. Our crystallographic analyses of AhpF also strongly support the involvement of large domain movements in the catalytic cycle of AhpF. Crystallographic and fluorescence approaches will be used in the third specific aim to define the nature of AhpF-AhpC interactions as well as inter- domain interactions within AhpF during intrasubunit electron transfer. Understanding of catalysis by bacterial AhpF and both bacterial and mammalian AhpC homologues will contribute to our knowledge of oxidative stress defense mechanisms and redox-regulated cell signaling in both pathogens and mammalian hosts. Therapeutic intervention in preventing oxidative damage involved in human degenerative diseases, cancer and aging as well as in combating pathogenic defense systems requires a complete molecular and biological understanding of the alkyl hydroperoxide reductase enzymes from both bacterial and human sources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDICAL HISTORY, MEDICATIONS, AND PANCREATIC CANCER RISK Principal Investigator & Institution: Mandelson, Margaret T.; Associate Investigator; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005

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Summary: (provided by applicant): Risk factors for pancreatic cancer are not well established. The goal of this pilot study is to investigate the relation between medical history, medication use and pancreatic cancer in a case-control study based on medical record abstraction and electronic laboratory and pharmacy data. Our specific aims are: 1. To investigate the relation between medical conditions and pancreatic cancer risk, focusing on: a. Diabetes mellitus, including disease duration, therapy, and glycemic control. b. Pancreatic inflammation, including acute and chronic pancreatitis. c. History of peptic ulcer disease and/or infection with Helicobacter pylori (H. pylori). d. History of cholecystectomy and/or cholelithiasis. 2. To investigate the relation between the use of medications and pancreatic cancer, focusing on nonsteroidal anti-inflammatory drugs, cholesterol lowering agents including HMG-CoA reductase inhibitors and acid suppressive medications including histamine receptor antagonists and proton pump inhibitors. As a secondary specific aim we propose to examine additional medical conditions and medications in order to generate hypotheses for future studies of the epidemiology and prevention of pancreatic cancer. These include evaluation of medical conditions such as irritable bowel syndrome, allergies and asthma as well as medications including immunosuppressive medications and angiotensin converting enzyme inhibitors. To meet these specific aims we propose to conduct a case-control study of pancreatic cancer comprised of 250 newly diagnosed cases and 1,000 controls in the defined population of Group Health Cooperative, a large health maintenance organization. Data on prior medical conditions and medications will be collected through abstraction of traditional and computerized medical records, including electronic laboratory and pharmacy data. Study strengths include the availability of uniformly collected, long-term medical and pharmacy data and the availability of data on important covariates, including smoking. The proposed study will provide a unique opportunity to investigate the role of medical conditions and medications in pancreatic tumorigenesis and to generate new insights into the mechanisms that result in pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODEL STUDIES OF ACETYL COENZYME A SYNTHASE Principal Investigator & Institution: Riordan, Charles G.; Professor; Chemistry and Biochemistry; University of Delaware Newark, De 19716 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The proposed research is designed to elucidate the mechanistic parameters of the elementary steps catalyzed by the nickel- containing acetyl-coenzyme A synthase (ACS) using well-defined low molecular weight systems. Included among these steps are the nonenzymatic transfer of a methyl group from the corrinoid protein (C/Fe-SP) to the A cluster, CO insertion into the CH3-A cluster bond and thiolate addition to the CH3C(O)-A cluster. To this end, first it will be necessary to prepare synthetic analogs that contain the key features of the catalytic site (A cluster). A structural model consistent with all spectroscopic data (an X- ray structure is not available) includes a single nickel ion in a (N/O)2S2 donor environment linked through a covalent bridge, X, to an [Fe3S4]2+ cluster. Chemical reactivity studies will entail probing stoichiometric transformations using the synthetic analogs. Individual reactions will be systematically interrogated using the protocols of mechanistic inorganic chemistry including product analyses, kinetic measurements, stereochemical and radical clock probe investigations. The long- term goal of this project is to develop a detailed mechanistic understanding of how the structural, electronic and chemical properties of biological heterometallic clusters are optimized for the intended catalytic transformations. The proposed research

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impacts our understanding of the biological implications of the essential trace element nickel that include the virility of Helicobacter pylori which has been associated with peptic ulcer disease, gastric carcinoma, and gastric lymphoma, and carcinogenesis through production of oxidizing species that degrade DNA. Additionally, acetongenic and methanogenic bacteria, organisms that contain ACS, may be important to human digestive function and dysfunction as they occupy a large volume of the colon. More broadly, a deeper understanding of ACS is valuable to our fundamental understanding of the general class of biological heterometallic assemblies, e.g. the catalytic sites in [NiFe] hydrogenase, sulfite reductase, cytochrome c oxidase, [CuZn] superoxide dismutase and the nitrogenase cofactor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODIFICATION OF HELICOBACTER PYLORI LIPID A Principal Investigator & Institution: Trent, Michael S.; Microbiology; East Tennessee State University Box 70565 Johnson City, Tn 37601 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The outer membrane of Gram-negative bacteria consists of a unique molecule known as lipid A that serves as the membrane anchor for lipopolysaccharide (LPS). Lipid A (endotoxin) is the component of LPS responsible for the stimulation of the host innate immune system involved in Gram- negative sepsis. The lipid A of Escherchia coli is a hexa-acylated disaccharide of glucosamine that is substituted at the 1- and 4'- positions with phosphate and glycosylated at the 6' position with two Kdo (3-deoxy-D-manno-octulosonic acid) moieties. Nine enzymes are required for biosynthesis of Kdo2- lipid A, the minimal LPS required for E. coli growth under normal laboratory conditions. Since lipid A is required for bacterial growth, it has become an interesting target for the design of novel antibacterial agents. Although single copies of the lipid A biosynthetic genes are found in nearly all Gram-negative bacterial genomes including those of Helicobacter pylori, the lipid A of the latter is underacylated with the phosphate groups either absent or modified. The primary focus of the present study is the identification of novel enzymes required for the modification of H. plyori lipid A and initial studies to evaluate the importance of such modifications during infection. Secondly, the lipid A structure of Helicobacter heilmannii will be investigated. H. pylori is now considered the causative agent of gastric and duodenal ulcers and H. heilmannii has recently been found associated with human gastritis. The specific aims of the current proposal are: (I) characterization and cloning of lipid A deacylases of H. pylori; (II) characterization and cloning of genes required for modification of the phosphates of H. pylori lipid A; (III) relevance of H. pylori lipid A modifications during infection; and (IV) isolation, purification, and structural characterization of key lipid A species of H. heilmannii. The completion of these aims will not only further the understanding of the lipid A biosynthetic pathway in H. pylori and H. heihnannii but also lay the foundation for new molecular insights into the pathogenesis of these unique organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR EPIDEMIOLOGY OF BARRETTS ESOPHAGUS AND CANCER Principal Investigator & Institution: Whiteman, David C.; Queensland Institute of Medical Research Herston Brisbane Qld, 4006 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): The incidence of adenocarcinoma (AC) of the esophagus has increased rapidly in most countries during the past three decades, yet the reasons are not well understood. AC typically arises on a background of Barrett's esophagus (BE). At the population level, relatively little is known about the environmental and genetic causes of BE and AC, or about factors which modify the natural history of BE to cause progression to cancer. In this population-based study, we aim to quantify the risks associated with exposure to epidemiologic and genetic risk factors for reflux esophagitis (RE), BE and AC. In parallel biospecimen analyses, we aim to identify molecular subtypes of BE and AC using microarray gene expression profiling and tissue arrays. To accomplish these aims, we will sample representative groups of patients with biopsyproven RE [n=400], BE [n=700] or AC [n=300] from all pathology laboratories servicing the target populations during a 3 year period, and compare them with two groups of controls. A representative group of population controls [n=600] will be sampled from a compulsory electoral register, and a group of biopsynegative tissue controls [n=400] will be sampled from the pathology laboratories. Cases and controls will answer identical questionnaires, focusing on gastro-intestinal symptoms, exposure to medications (especially reflux promoters, NSAIDs, COX-2 inhibitors, hormones), as well as smoking, alcohol, infection with Helicobacter pylori and family history of cancer. Blood samples will be collected from participants to identify genotypes associated with predisposition to RE, BE and AC. From cases and tissue controls, we will obtain specimens of biopsy or surgical tissue with the aim of determining the prevalence of molecular subtypes of BE and AC. Fresh tissue will be available from a proportion of clinic-based AC cases [n=50-100] for gene discovery through microarray gene expression profiling. From comprehensive mining of the expression profiling data we will identify diagnostic markers for the different subtypes of BE and AC, prognostic markers that predict likelihood of progression and/or response to therapy, and targets for rational drug design to treat BE and AC. Candidate genes will be validated in the paraffin sections available for all cases and tissue controls using tissue array technology. Epidemiologic analyses will then be performed comparing risks of exposure among the major disease groupings (RE, BE, AC), as well as for the molecular subtypes of RE, BE and AC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOSAL IMMUNITY AND INFECTION Principal Investigator & Institution: Lamm, Michael E.; Professor; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 30-JUN-2005 Summary: OVERALL (Adapted from application): This Program Project Application is submitted by an interactive group of basic and clinical scientists who propose to continue to study the mucosal immune system inr elation to parasitic, bacterial and viral infections. The proposed research focuses on the broad areas of pathogenesis, prevention and therapy of important diseases caused by different classes of infectious agents that infect the gastrointestinal, genital and respiratory mucosae. Project 1 addresses Entamoeba histolytica and amoebiasis, a leading cause of parasitic death and morbidity worldwide. The specific studies focus on the galactose-inhabitable lectin, that mediates the binding of Entamoeba to the intestinal epithelium. The goal is to identify immunogenic subdomains of the lectin that can be used to develop an effective oral subunit vaccine. The second project is on Helicobacter pylori, the major cause of peptic ulcer disease. Based upon studies of pathogenesis and mechanisms of immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an

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untoward inflammatory immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an untoward inflammatory immune response. Project 3 investigates how mucosal IgA antibodies can counter HIV at epithelial surfaces that are the portals of entry for sexual transmission of this virus. Monoclonal IgA antibodies to HIV, both extracellular and intracellularly. The mechanisms of action of such protection will be studied. The results may further the design of an effective mucosal vaccine for this sexually transmitted disease. The fourth project investigates IgA nephropathy, the most common type of glomerulonephritis, that is associated clinically with respiratory infection The roles that normal and aberrant IgA glycosylation, virus-specific T cells and glomerular mesangial cells play in disease pathogenesis will be investigated in a post infection mouse model in nephritis-sensitive and nephritis-resistant strains. The four projects are supported by administrative and hybridoma cores. The insights to be gained from this PROGRAM Project may e broadly applicable since many infections involve mucous membranes, either as sites of infection or as portals of entry into the host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOSAL IMMUNOLOGY OF HELICOBACTER INDUCED GASTRITIS Principal Investigator & Institution: Czinn, Steven J.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 15-DEC-1993; Project End 30-NOV-2002 Summary: (Adapted from the applicant's abstract): Since the rediscovery of Helicobacter pylori (H. pylori) in the early 1980's, studies have now demonstrated that H. pylori plays an etiologic role in the development of gastritis, peptic ulcer disease, and gastric cancer. The investigators have previously demonstrated the importance of the host as a factor in disease outcome following gastric Helicobacter infection. A related issue, is whether the host immune response contributes to the pathogenesis or acts to protect the host from infection. Using the H.felis/mouse model, the investigators have demonstrated that the T-cell mediated immune response to Helicobacter infection can contribute either to the pathogenesis or act in concert with the humoral immune response to clear this infection. Specifically, the results of studies funded during the previous granting period indicate the Helicobacter infection activates antigen specific cell-mediated immune responses in immunized or infected hosts. These responses have a phenotype which is either pro-inflammatory in nature (TH1) or protective in nature (TH2). Adoptive transfer of Helicobacter-specific TH1 lymphocytes exacerbates gastric inflammation in recipients. However, transfer of a TH2 cell line from immunized/protected mice decreases the magnitude of infection in the recipients. There continues to be a number of unanswered questions, however, which are the focus of this proposal. Using the recently developed H. pylori/mouse model, a number of contemporary techniques, such as the use of knock-out or transgenic mice, recombinant cytokine therapy, and adoptive transfer studies, will be used to further investigate the role of the host immune response in preventing or promoting chronic H. pylori gastroduodenal disease. the investigators will specifically assess the contribution of the humoral immune system in preventing H. pylori gastroduodenal disease following immunization as well as assess the contribution of the host cellular immune response in preventing or promoting H. pylori gastroduodenal disease. An in-depth understanding of the pro-inflammatory mechanisms employed by the host in this model will contribute to our general understanding of immune regulation and the pathogenesis of infectious disease. Finally, these aims are a logical extension of the work previously performed in

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their laboratory and may ultimately allow them to develop a safe and efficacious subunit vaccine to prevent morbidity and potential long-term consequences of Helicobacter infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NETWORK-BASED ANALYSIS OF KINETICS AND REGULATION Principal Investigator & Institution: Palsson, Bernhard O.; Professor; Bioengineering; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Extreme pathways are a unique, network-based, mathematical definition of metabolic pathways and thus can be used to rigorously define and study the emergent properties of biological systems. They are derived directly from the stoichiometric matrix that represents a biochemical network and completely characterize all possible steady-state flux distributions through the network. Extreme pathways have already given many insightful conclusions about the topological properties of reconstructed reaction networks and their relationships to biological functionalities. However, the utility of extreme pathways is currently limited by the fact that the complete enumeration of genome-scale extreme pathways is computationally challenging. Additionally, the development of new analysis tools is needed to strengthen the link between extreme pathway properties and experimental data. Accordingly, our specific aims are to: (1) enable the efficient calculation of extreme pathways from genome-scale models; (2) apply the techniques developed in Specific Aim #1 to compute the extreme pathways for: (a) organelles (the mitochondria from Saccharomyces cerevisiae and chloroplasts from Arabidopsis thaliana), (b) growth condition dependent human pathogens (Helicobacter pylori and Haemophilus influenzae and others that may become available during the period of this proposal), and (c) a fully autonomous organism Escherichia coil); and (3) develop analysis tools to yield more biological meaning and relevance of extreme pathways by analyzing singular value decomposition (SVD) of extreme pathway matrices and converting the flux cone into a cone of kinetic constants (the K-cone) using measured concentrations (proteomics and metabolomic data). The concepts and analysis methods developed and verified to date must be moved forward to tie concepts directly to biological data and applications. If implemented, this proposed program will result in a significant advancement in our ability to study and characterize the capabilities of reconstructed networks and to relate in silico results to actual cellular functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ONE-STEP H. PYLORI TEST: SCREENING AND INDIVIDUAL ASSAYS Principal Investigator & Institution: Goodridge, Carolyn F.; Cc Technology, Inc. Box 3136, 813 S 2Nd St Laramie, Wy 82071 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: The aim of this project is to demonstrate feasibility of four different types of H. pylori assays. Assays will be developed for both the H. pylori organism and its antibody. The specific goal will be to develop a test which is rapid and very-low cost for screening of populations and for clinical laboratories. H. pylori is significant as a cancer risk as it can cause two types of malignancies: gastric adenocarcinoma and primary gastric MALT lymphoma. The gastric adenocarcinoma is the second leading cause of cancer death around the world and it is expected by 2010 to be the eighth leading cause

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of all death. The method proposed is a Surface Enhanced Raman ImmunoAssay (SERIA) that has several significant advantages. Foremost, the surface localized enhancement of the SERIA method eliminates spectroscopic interference from matrix effects. Furthermore, it eliminates the need for washing steps that create biohazardous waste and personnel exposure in other immunoassays configurations. The project will examine sensitivity, selectivity, shelf-- life, and cost of production for H. pylori SERIA. The SERIA will be optimized with sterile buffer solutions. Once typical protocols are established with buffers we will examine animal samples supplied in the for of mice tissue, blood, feces, and gastric juices. When optimization with the animals samples has been established we will look at human blood. tissue, feces, and vomitus samples. Comparisons will made to commercially available kits. PROPOSED COMMERCIAL APPLICATIONS: The number one goal of this project is to produce a microwell format assay for H. pylori. Secondary is a single sample format for low-volume testing The market for the first goal is wide open as no high-volume low-cost procedure exists. The market would be instruments and assays for screening large populations for H pylori infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE DAMAGE TO GASTRIC EPITHELAL CELLS BY H PYLORI Principal Investigator & Institution: Crowe, Sheila E.; Associate Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 21-SEP-2001; Project End 31-AUG-2006 Summary: Helicobacter pylori is a chronic infection that affects 50% of the world's population causing gastritis in all infected while only a subset develop disease of the epithelium in the form of ulceration or adenocarcinoma. Both bacterial and host factors appear to play a role in the pathogenesis of these human diseases but the specific mechanisms remain unclear. H. pylori and cytokines known to be increased in H. pylori infection, induce alterations of gastric epithelial cell growth such as the induction of programmed cell death. Phagocytic leukocytes recruited to the gastric mucosa during infection become activated, generating reactive oxygen species (ROS) that we have shown to alter gastric epithelial cell growth and induce apoptosis. Infection with H. pylori also induces the accumulation of ROS in gastric epithelial cells that may be dependent on bacterial genotype. Gastric epithelial cells respond to oxidative stress with the initial generation of ROS and subsequent activation of a redox-sensitive signaling pathway which has been shown to control the transcription of genes that regulate cell growth, repair and death processes. Of particular interest is ROS-induced activation of apurinic/apyrimidinic endonuclease-1 (AP endonuclease), a multifunctional protein that is the rate-limiting enzyme in the DNA base excision repair pathway of oxidative lesions, which also activates transcription factors including activator protein (AP)-1, and p53. Thus, the general hypothesis underlying this proposal is that oxidative stress contributes to the epithelial cell injury that occurs during H. pylori infection. The specific hypothesis that H. pylori infection stimulates redox-sensitive signaling through AP endonuclease that leads to apoptosis in gastric epithelial cells will be examined in the following specific aims: Aim 1. Evaluate oxidative stress in gastric epithelial cell injury (apoptosis) during H. pylori infection; Aim 2 Determine if H. pylori regulates the expression and function of AP endonuclease in gastric epithelial cells; Aim 3. Define how AP endonuclease regulates apoptosis and the transcription of pro-apoptotic genes. These studies in cultured human cell lines and human tissue will address unanswered questions regarding the effect of oxidative stress on gastric epithelial cell injury. The

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molecular mechanisms governing the epithelial response to oxidative stress will also be defined. This new knowledge will improve our understanding of the pathogenesis of epithelial cell damage associated with H. pylori infection and help identify strategies for the prevention and treatment of human gastric disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND SURVIVAL OF HELICOBACTER PYLORI Principal Investigator & Institution: Maier, Robert J.; Professor; Microbiology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by the applicant): Helicobacter pylori is a spiral bacterium that colonizes the gastric mucosa of humans, leading to a variety of inflammatory gastric diseases that include peptic ulcers, chronic gastritis, adenocarcinoma of the lower stomach, and MALToma (mucosal-associated lymphoma). The severity of the inflammatory-based disease is related to the persistent nature of the pathogen, and chronic infection is the predominant pre-disposing factor for carcinoma. The persistence is attributed to the pathogens' stringent adaptation to the harsh environment of the human stomach, which must include avoiding acidity and combating host defense mechanisms. The battery of host-produced partially reduced oxygen species and other reactive molecules that damage the bacterial cellular components needed for survival of the pathogen are in turn counteracted by enzymes produced by the successful pathogen. The goal is to identify and characterize the antioxidant enzymes produced by H pylori to combat oxidative stress and maintain virulence (stomach colonization). This will be approached by targeted mutagenesis of five specific antioxidant genes. Then each mutant will be characterized for its ability to withstand oxidative stresses, to acquire spontaneous mutations, to survive air-exposure, and to colonize mouse stomachs. The environmental host-related signals (such as iron, oxygen, mucin, pH, and oxidizing agent) that may regulate each of the five genes will be determined, and some of the antioxidant activities will be characterized. In addition to the five targeted antioxidant activities, global approaches involving proteomics and DNA microarray will be used to determine the number and nature of proteins that are expressed upon adaptation of H pylori to oxidative stress conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOLOGIC INFLUENCES MODULATING GASTRIC EPITHELIAL DIFFERENTIATION Principal Investigator & Institution: Merchant, Juanita L.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic inflammation of the gastric mucosa (chronic gastritis) may occur from Helicobacter pylori infection or bacterial overgrowth in the hypochlorhydric stomach. The central question posed in this Subproject is how does reduced stomach acid trigger the reversion of the gastric epithelium to cells with small bowel characteristics? Recently, we have confirmed in a hypochlorhydric mouse model that reduced stomach acid coincides with bacterial overgrowth and changes in the epithelium reminiscent of H. pylori infection in patients. Since bacterial colonization of the stomach induces an inflammatory response, it is difficult to study the contribution from bacterial gene products versus the inflammation. Therefore to distinguish between these two components of chronic gastritis, we will study transgenic mice expressing the

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H. pylori gene product CagA and wild type mice treated with the pro-inflammatory cytokine interferon gamma (INF-gamma). INF-gamma was selected since it is the major Th1 cytokine secreted during H. pylori infection. Recently, CagA was shown to translocate into the cytoplasm of human gastric cells suggesting that this event may be one signal triggering the cascade of events. However, the role of a specific bacterial virulence factor on the pathogenesis that is observed has not been studied. Over time, the inflammatory process progresses and alteration of the epithelial cell population occurs which includes gradual loss of parietal cells with increased infiltration and proliferation of mucous cells. Proliferation of the mucous cell types and evidence of an intestinal phenotype with villin expression (intestinal metaplasia) is a major precursor lesion for gastric cancer. Overall, the specific goals of this project are to understand the impact of bacterial infection on gastric epithelial cell differentiation. The specific aims of the project are: 1) Study how H. pylori CagA modulates the pattern of gastric epithelial cell differentiation in vivo. 2) Study how cytokines modulate gastric epithelial cell differentiation in vivo. 3) Dissect the signaling pathways activated by CagA that regulate cell survival. 4) Study aberrant expression of villin in the stomach after bacterial colonization. The studies proposed will advance our understanding of how cell differentiation is regulated in vitro and in vivo by bacterial gene products and cytokines. Further, clues as to how modulating the pattern of gastric epithelial cell differentiation is linked to the development of pre-neoplastic lesions in the stomach will be examined. In this manner, we hope to gain significant insight into how common pathologic influences affect gastric cell identity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOP/PHOQ DELETED S TYPHI VACCINE STRAINS Principal Investigator & Institution: Hohmann, Elizabeth L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: Vaccination is an effective and economical method of preventing disease, and multivalent, orally administered vaccines will have the widest clinical application. Attenuated Salmonella have been successfully studied in murine models as live vectors for delivery of heterologous antigens to the gastrointestinal immune system. Studies in humans have been limited, and variables important for immunogenicity in humans have not been clearly defined. A Salmonella typhi strain (Ty800) deleted for the phoP/phoQ virulence regulon of Salmonellae is very safe and immunogenic in human volunteers, and this strain has been modified to express clinically relevant heterologous antigens. This proposal describes a program of translational research designed to evaluate Salmonella-based vaccine regimens in humans utilizing bivalent S. typhi vaccine strains. These studies emphasize rational modification of clinically acceptable human vaccine strains and vaccination regimens which may alter immunogenicity of heterologous antigens such as type of antigen, location of antigen within the bacterial cell and mechanism of expression or secretion. Using an established IRB-approved human study protocol, adult volunteers are vaccinated, followed for safety and vaccine shedding, and intensively evaluated for evidence of mucosal, humoral and cellular immune-responses to both S. typhi antigens and the relevant heterologous antigens. A sequential oral vaccination regimen consisting of a S. typhi vaccine strain expressing cytoplasmic Helicobacter pylori urease followed by purified recombinant urease and E. coli heat labile toxin adjuvant will be tested in adult volunteers seronegative for H. pylori. An S. typhi strain expressing a fusion antigen of E. coli hemolysin A linked to urease B which is secreted from the bacterial cell will be studied to determine whether

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secretion alters immunogenicity in this system. Additional constructs will be generated which express either an E. coli heat labile toxin mutant or an E. coli colonization factor antigen (CFA/I). These new strains will be evaluated in vitro and subsequently tested in volunteers to determine whether these molecules with different structures or subcellular location can engender systemic and/or mucosal immune responses. These studies are designed to provide novel human safety and immunogenicity data which is vital to the clinical development of live bacterial vaccine vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECOMBINANT MURINE IL-10 PRODUCED IN SITU BY H. PYLORI Principal Investigator & Institution: Eaton, Kathryn A.; Associate Professor; Laboratory Animal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 15-DEC-2003; Project End 30-NOV-2005 Summary: (provided by applicant): H. pylori has been called the most common infectious disease of humans in the world today. Worldwide, between 50-100% of people are infected with H. pylori, but only a minority of those develop clinical signs of disease. Almost 2 decades of research have resulted in a general consensus that host immune response is a critical factor in determining the outcome of infection. Gastritis due to H. pylori is a T helper-1-mediated immune response associated with high levels of IFNgamma and low levels of IL-10 and other anti-inflammatory mediators. Understanding cytokine function in gastritis due to H. pylori has both diagnostic and therapeutic significance. First, identification of regulatory cytokines such as IL-10 or TGFbeta could lead to further understanding of regulatory pathways and development of therapies for those individuals with intractable infections. Second and perhaps equally important, such understanding could lead to the ability to identify individuals likely to be responders or non-responders. Individuals vary widely in their response to H. pylori, likely because of varying immunoreactivity of each individual host. Because of the strong association between IL-10 and immunoregulation of H. pylori responses, we have chosen to focus this pilot study on IL-10. Our overall goal is to test the hypothesis that recombinant murine IL-10 produced in situ by H. pylori ameliorates or prevents gastritis in mice. This goal will be accomplished in 2 specific aims: Aim 1: To engineer H. pylori to express recombinant murine IL- 10. Aim 2: To determine if in vivo expression leads to prevention or resolution of gastritis in response to recombinant bacteria or to wild-type H. pylori that co-colonize with recombinant strains. Briefly, we will construct recombinant H. pylori that expresses murine IL-10, demonstrate that the cytokine is expressed by bacteria in culture and in the mouse stomach, and determine if such expression ameliorates or prevents inflammation in a mouse model of severe gastritis. A successful outcome will not only determine the potential therapeutic role of IL-10 in gastritis due to H. pylori, but will also establish a model in which the roles of other cytokines and mediators can be determined, and host and bacterial interactions can be directly evaluated in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESEARCH TRAINING IN INFECTIONS AND IMMUNITY Principal Investigator & Institution: Tweardy, David J.; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008

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Summary: (provided by applicant): This is a new NRSA application to support two postdoctoral trainees per year for five years This award will substantially increase the ability of talented trainees to exploit outstanding opportunities to pursue research training in infectious diseases at Baylor College of Medicine. At this time, no NRSA exists within Baylor College of Medicine or the Texas Medical Center to pursue clinical research training in non-AIDS infections. Yet, there is increasing need for trained professionals capable of performing clinically based research directed at treatment and prevention of non-AIDS infections that threaten the health of US citizens, including ageold scourges such as infectious gastroenteritis and pneumonia and new threats posed by bioterrorism. Superb training opportunities exist at Baylor College of Medicine in a number of areas, including biodefense. Participating projects with a strong record of federal funding and training experience include: 1) Innate Immunity and Nosocomial Infections; 2) Parasitic Infections; 3) Viral and Bacterial Gastroenteritis; 4) Viral Oncogenesis; 5) Acute Respiratory Pathogens; 6) Vaccine Evaluations; 7) Tuberculosis; 8) Helicobacter pylori Infection; and 9) Prostheses Infections. Total grant support in 2002 for the specific centers and programs participating in this NRSA Program is $19,769,825. The structure of the Program for Research Training in Infections and Immunity will contain three components that represent general training tracks that can be pursued by trainees: 1) laboratory-based clinical research; 2) clinical research trials; and 3) clinical epidemiology. All trainees will be encouraged to participate in the Clinical Scientist Training Program at Baylor College of Medicine and obtain their Masters Degree in Clinical Investigation. Those pursuing the clinical epidemiology track may opt for a MPH Degree at the University of Texas-Houston School of Public Health. The Adult Infectious Diseases Training Program at Baylor College of Medicine has shown it can attract highly qualified postdoctoral trainees, half of them women and close to a quarter underrepresented minorities, and point them in the direction of future infectious diseases clinical research. In the past two years, this program has produced graduates who have successfully pursued each of the three training pathways proposed. Altogether, these four individuals have published 26 original peer-reviewed manuscripts and have been awarded several prestigious grants and career development awards, totaling $1,862,500. This recent track record is offered as evidence in support of the request for two postdoctoral trainees per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS AND GASTRIC DISEASE IN PEDIATRIC H PYLORI Principal Investigator & Institution: Gold, Benjamin D.; Professor; Pediatrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 30-SEP-2004 Summary: (taken from the application) Helicobacter pylori (Hp) is the major cause world-wide of chronic-active gastritis, primary duodenal ulcers, and is linked to gastric cancer. Most Hp infections are acquired in childhood; why some individuals develop symptomatic disease and others do not is unclear. Histopathological studies suggest that the degree and type of inflammatory infiltrate in gastroduodenal lesions are significantly different in Hp-infected children compared to adults. However, these differences remain unexplained. Studies of the host immune response following initial Hp infection in childhood and the relationship to Hp virulence factors (i.e., vacA) bolstered by the evaluation of host risk factors for infection are critical to understand the pathogenesis of Hp infection. Our preliminary studies of Hp infection in children developed accurate non-invasive methods for detection of infection and showed a unique gastric mucosal inflammatory response with increased numbers of

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macrophages. In vitro, we demonstrated the impotence of IL-8 and RANTES chemokines for leukocyte activation and recruitment. Furthermore, we demonstrated a difference in the T-cell responses of Hp-infected versus uninfected patients. Overall hypothesis: among Hp infected children, there are host factors (i.e., ethnicity) and environmental cofactors (i.e., water source) which result in symptomatic disease and children with symptoms will be infected by virulent Hp strains and have a more significant mucosal inflammatory response. Specific aims: 1) determine the host factors and environmental cofactors necessary for symptomatic Hp infection in children. Hpinfected symptomatic endoscopy cases at 4 centers will be compared to age, gender and region-matched Hp-infected asymptomatic controls. 2) characterize the bacterial properties (i.e., phenotype, genotype) associated with pediatric Hp infection. The phenotype and genotype prevalence of Hp isolates obtained from infected cases will be evaluated in comparison to gastroduodenal disease severity. 3) characterize the host inflammatory response of Hp-infected children. The histopathology in comparison to the chemokine and cellular response in the gastric mucosa of infected children will be determined. The proposed research provides a systematic examination of the association between Hp strains and host exposure characteristics and the severity of clinical disease in children. These studies are prerequisite for understanding the host-bacterial interaction in initial infection and evolution of gastroduodenal inflammation and overall pathogenesis of Hp. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF FAS/NF KB IN H.PYLORI INDUCED GASTRIC CARCINOMA Principal Investigator & Institution: Houghton, Jeanmarie; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 26-SEP-2001; Project End 31-AUG-2004 Summary: (provided by Applicant) Helicobacter pylori infection causes a spectrum of gastric and duodenal pathology ranging from hyperproliferation and adenocarcinoma to severe tissue loss (ulcers). How the bacterium causes these paradoxical disease outcomes is not understood. Recent studies, including those from our laboratory, have shown that Fas apoptotic signaling plays a significant role in the pathogenesis of helicobacter-induced ulcer disease by initiating cell death programs. In addition, preliminary results strongly suggest a direct role for the Fas signaling pathway in modulating gastric mucosal cell proliferation (in addition to cell death) through induction of NF-kB. Nuclear factor activation has been suggested to positively regulate cell proliferation and promote survival, potentially allowing for mutations within abnormally proliferating cells leading to cancer formation. The experiments proposed in this application are aimed at determining the role and mechanism of Fas-induced aberrant gastric epithelial cell proliferation. We w i l l determine the mechanism of modulating Fas signaling towards a proliferative response and the specific roles of well established components of the Fas pathway in eliciting this response. To accomplish these goals, we will engineer gastric mucosal cell lines which transduce proliferative signaling by manipulating Fas Ag expression (constitutively or inducibly). This approach will be followed with gene-knockout strategies to isolate roles of candidate signaling molecules that mediate this response. The information gained in the controlled in vitro setting will be utilized for the development and characterization of in vitro models. Exploitation of newly engineered Fas Ag and Fas L deficient radiation chimera murine models as a more complex, rigorous and clinically relevant in vivo gastric mucosal environment will allow for the study of the importance of Fas proliferative

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signaling. Mechanisms which allow aberrant proliferation may contribute to carcinogenesis by inhibiting death and promoting cell division in cells which have accumulated genetic defects. Defining the regulation of these pathways will help define the complex relationship helicobacter shares with its host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ADENOCARCINOMA

OF

H.

PYLORI

INFECTION

IN

ESOPHAGEAL

Principal Investigator & Institution: Tchou-Wong, Kam-Meng M.; Assistant Professor; Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining. The decreasing prevalence of cagA+ Helicobacter pylori may be associated with the rising incidence of esophageal adenocarinomas in industrialized countries. Colonization with cagA+ strains has been shown to be inversely associated with reflux esophagitis and Barrett's esophagus. A lower prevalence of cagA+ Helicobacter pylori has been observed in patient with gastroesophageal reflux disease (GERD) which results from acid exposure to the esophagus. One explanation for the negative association between colonization with Helicobacter pylori and GERD is the effect of Helicobacter pylori on acid production. Eradication of Helicobacter pylori has led to the development of GERD in a proportion of treated patients. These clinical evidence has led to the hypothesis that Helicobacter pylori could play a protective role in the development of GERD, especially reflux esophagitis. Experiments proposed in the following specific aims will test the hypothesis that Helicobacter pylori, especially the cagA+ strains, may protect against GERD, Barrett's esophagus and esophageal adenocarcinoma. The specific aims are as follows: 1. To study the effects of gastric colonization of cagA+ and cagA- strains of Helicobacter pylori on host inflammatory responses in rats and mice. 2. To determine the effects of Helicobacter pylori infection in reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in rats. 3. To determine the effects of Helicobacter pylori infection in esophagitis, Barrett's esophagus and esophageal adenocarcinoma in a surgical reflux model in wild-type and p53 knockout mice. The proposed studies aim to ascertain the role of Helicobacter pylori colonization in the development of reflux esophagitis, Barrett's esophagus and its associated adenocarcinoma in rodent models. This proposal utilizes the innovative surgical models of GERD, BE and EAC for studying the protective role of Helicobacter pylori against reflux complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLES PATHOGENESIS

FOR

MOTILITY

IN

HELICOBACTOR

PYLORI

Principal Investigator & Institution: Ottemann, Karen M.; Environmental Toxicology; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The bacterium Helicobacter pylori inhabits the stomachs of a full 3 billion people--half the world's population. Infections with this bacterium cause significant morbidity and mortality around the globe. In the majority of cases, the bacterium establishes chronic infections that lead to diverse outcomes ranging from asymptomatic carriage to ulcer disease to gastric cancer. Conservative estimates suggest that 5 percent

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of those infected-150 million people-develop some form of disease. H. pylori has the dubious distinction of being the only bacterium classified as a Group I carcinogen by the International Agency for Research on Cancer of the World Health Organization. Infection by this bacterium is a risk factor for several types of gastric cancer including gastric adenocarcinoma and mucosa- associated lymphoid tissue (MALT) lymphoma. The processes used by H. pylori to establish and maintain infection are just beginning to be worked out. One such process is the ability to swim. H. pylori is motile via organelles called flagella, and it must have functional versions of these organelles in order to colonize animal stomachs. In addition, H. pylori does not swim randomly but instead directs its motility in response to environmental cues in a process called chemotaxis. We are interested in understanding how chemotactic motility is used for infection by this bacterium. Towards this we propose three aims: (i) Ascertain at what points during infection chemotactic motility is used by H. pylori. (ii) Determine how H. pylori chemotaxis is directed by pinpointing which of its chemoreceptors are used for mouse stomach colonization, and to what they respond. (iii) Dissect how information is relayed from the chemoreceptors to the flagellar motor during chemotactic signal transduction in H. pylori by analyzing how a family of proteins, the CheVs, function. Chemotaxis is observed in a number of bacterial pathogens but little is known about its role during infection. What we learn from these studies may apply to other bacteria. For example, the Campylobacter group of bacteria are leading causes of food-borne diarrheal disease, and similarly require motility and chemotaxis for infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SENSING PH AT THE GASTRIC SURFACE Principal Investigator & Institution: Montrose, Marshall H.; Professor; Physiology and Biophysics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: The stomach must survive HCl secreted by the gastric epithelium. This challenge is heightened by the frequent presence of compounds (e.g. non-steroidal antiinflammatory drugs) or organisms (Helicobacter pylori) which compromise the gastric barrier to acid, leading to ulcers when the barrier is breached. An alkaline juxtamucosal gel layer is the first line of gastric defense: acting to protect the gastric epithelium from back-diffusion of acid from the lumen. We have developed a unique approach to noninvasively measure pH at the gastric surface in vivo. Using confocal microscopy, we have imaged a juxtamucosal alkaline layer, which converts to an acid layer when luminal pH is changed to values found in the fed stomach. Our results suggest a new model of gastric surface pH regulation, which includes a substantial change in the transporters that control surface pH. Our objective is to define the elements regulating luminal pH sensing and surface pH regulation in the stomach. Using primarily in vivo confocal microscopy of rat or mouse stomach, our first aim will define fundamental requirements for the stomach to sense and respond to luminal pH. We will a) define the timing and location of luminal pH change required for conversion from alkali to acid secretion, and b) test the role of luminal nutrients and buffers in surface pH regulation. In the second aim, we will question which molecules are transducers of the luminal pH stimulus that mediate the integrated regulation of both gastric acid and alkali secretion. We will focus on the role of somatostatin, PGE2, and capsaicin-sensitive afferent nerves containing CGRP. The role of somatostatin will be analyzed using antagonists and agonists selective for the somatostatin type 2 receptor (SST2) with parallel studies of SST2-knockout mice. The role of prostaglandin synthesis will be approached using

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selective inhibitors of known cycloxygenase (COX) isoforms, with parallel studies of COX-1 and COX-2 knockout mice. Capsaicin-sensitive afferents will be analyzed using vanilloid receptor agonists, CGRP receptor agonists and antagonists, with parallel studies of chemically deafferented animals. The third aim will ask how gastric mucosal damage disrupts surface pH regulation. We will generate microscopic lesions in the gastric epithelium by two-photon microscopy. Using this new model of focal gastric damage, we will follow the disruptions in surface pH regulation and the tissue repair process in real time. We will ask if aspirin, a major cause of clinical mucosal damage, weakens the gastric barrier by disruption of luminal pH sensing and surface pH regulation in normal and COX-knockout mice. We will determine if aspirin affects the repair of focal lesions created by two-photon microscopy. Results will integrate understanding of gastric defense with regulation of acid and alkali secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION RESPONSE IN HELICOBACTER PYLORI Principal Investigator & Institution: Forsyth, Mark H.; Biology; College of William and Mary Williamsburg, Va 23187 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): Genome sequencing of numerous prokaryotes has revealed a tendency toward decreased genetic investment in signal transduction machinery in species that exist in restricted ecological niches. Bacterial signal transduction systems are typically comprised of a sensory histidine kinase protein and a cognate transcription factor, known as a response regulator. Bacterial species capable of growth in multiple environments have large numbers of signal transduction systems, as many as 63 separate systems. Bacteria that are restricted to a pathogenic lifestyle and have no known environmental reservoir possess many fewer systems to detect and respond to environmental changes. Helicobacter pylori, the etiologic agent of peptic ulcer disease as well as gastric adenocarcinoma, appears to inhabit exclusively the human gastric mucosa. Genome sequencing of this bacterium reveals only 4 signal transduction pathways. This implies a somewhat limited repetoire of signals to which this pathogen can respond. This proposal takes advantage of the complete genetic characterization of two distinct pathogenic strains of H. pylori to examine the role of one specific signal transduction system in the control of gene expression. The studies described here will facilitate the determination of signals in the gastric ecosystem that serve as cues for H. pylori to alter its gene expression pattern. This will be accomplished by identifying genes used in the adaptive response to these environmental signals. These studies will utilize H. pylori mutants which are "blinded" to an aspect of their environment due to the targeted destruction of genes encoding a sensory protein. Utilizing whole-genome transcriptional profiling by means of DNA microarrays, the regulatory events comprising the adaptive response in this gastric pathogen will be mapped and the genes of the adaptive response will be characterized. Determination of the identity of genes whose transcription is regulated will allow potential environmental cues to be inferred and then experimentally determined. Similarly, use of recombinant transcription factors (response regulators) will allow the isolation of critical DNA sequences necessary to accomplish regulation of gene expression. Understanding of the gastric environment, as perceived though the sensory apparatus of H. pylori, will allow a better understanding of H. pylori pathogenesis and a more rational design of interventions into the infectious process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE PATHOGENESIS

OF

PROTEINS

INVOLVED

IN

119

BACTERIAL

Principal Investigator & Institution: Hultgren, Scott J.; Professor; Biochem & Molecular Biophysics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUN-2001; Project End 30-APR-2006 Summary: Bacterial pathogenesis involves at least two steps: 1- attachment of the bacteria to the host tissue to be infected, and 2- secretion of toxic molecules by the bacteria. Both steps are mediated by a fibrous structure displayed at the surface of the bacteria called a "pilus". On one end of the pilus (facing outwards), the pilus harbours a protein called "adhesin" which binds specifically to the host's surface polysaccharides. On the other end, the pilus may be attached to a secretion machinery responsible for injection of toxic substances. The pilus itself is a complex polymer of several different protein subunits. In this proposal, we propose to study the structural basis of 1- pilus biogenesis, 2- bacterial attachment to the host tissue, and 3-protein secretion. We have used the type P pili of uropathogenic Escherichia coli as a model to study pilus biogenesis and bacterial attachment, and we have used the type IV secretion system of the ulcer-causing Helicobacter pylori as a model to study the secretion of proteins by bacteria. We have obtained several crystals of pilus subunits in complex with their assembly chaperone; we have also crystallized binary complexes of adhesins with their cognate polysaccharides; and finally, we have crystallized important components of the type IV secretion machinery. Two of these structures have been or are in the process of being solved. Our proposal, by seeking to understand the structural basis of pathogenicity in bacteria responsible for important infectious diseases, will have not only an impact on the fundamental knowledge of the various systems under study, but will also help design antibiotic compounds which are effective in the fight against these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE-FUNCTION ANALYSIS OF H. PYLORI VACA Principal Investigator & Institution: Cover, Timothy L.; Associate Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-MAY-2006 Summary: (provided by the applicant): Colonization of the human gastric mucosa by Helicobacter pylori is associated with an increased risk for development of peptic ulcer disease and distal gastric adenocarcinoma. Studies in a mouse model for H. pylori infection indicate that expression of a toxin (VacA) enhances the capacity of H. pylori to colonize the stomach, and immunization of mice with VacA results in protective immunity. VacA contributes to gastric mucosal damage, and analysis of vacA alleles in H. pylori isolates from humans suggests that VacA plays a role in the pathogenesis of peptic ulcer disease. The effects of VacA on eukaryotic cells include vacuolation, altered trafficking within the endocytic pathway, membrane channel formation, and apoptosis. The VacA mechanism of action remains incompletely understood. Based on our preliminary studies, we hypothesize that the mature VacA toxin can be divided into three functional domains: (i) an N-terminal hydrophobic region (amino acids 1-32) involved in membrane insertion, transmembrane protein dimerization, and membrane channel formation; (ii) an N-terminal region (amino acids 33-422) that is required for intracellular toxin activities (cell vacuolation and apoptosis); and (iii) a C-terminal domain (amino acids 423-821) involved in binding of VacA to eukaryotic cells. This proposal outlines plans for in-depth structure-function analysis of these three domains.

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We will use multiple experimental approaches, including several mutagenesis strategies, assays of VacA channel activity, an in vitro system for analyzing peptide insertion into membranes, expression of recombinant VacA, a system for intracellular VacA expression, mapping of VacA structure with recombinant anti-VacA antibodies, and use of a mouse model to examine the functions of VacA in vivo. These studies should result in a better understanding of VacA structure and function, and insights into the VacA mechanism of action. Ultimately, these studies may lead to advances in the treatment or prevention of H. pylori-associated human diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURES AND DYNAMICS OF CHEA KINASE AND ITS COMPLEXES Principal Investigator & Institution: Crane, Brian R.; Chemistry and Chemical Biology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The protein histidine kinase CheA is central to signal transduction pathways that allow prokaryotes to sense and respond to their environments. During chemotaxis, CheA couples changes in ligand occupancy of transmembrane chemoreceptors to phosphorylation of the response regulator CheY; CheY controls the flagellar motor. In understanding the well-characterized phosphorelay of chemotaxis, central unanswered questions concern how receptor occupancy regulates kinase activity and how CheA coordinates phosphate flow from ATP to response regulators via an internal phosphorylation site. To address these issues we propose synergistic biophysical experiments centered on the crystallographic structure determinations of dimeric CheA in complex with receptor fragments and the receptor coupling protein CheW. To complement structures, solution studies will probe CheA dynamics and partner interactions. Relative CheA domain motions and subunit associations likely control interactions with its signaling partners. Crystals of CheA in complex with CheW and nucleotides will reveal new aspects of CheA catalysis and regulation. Soluble fragments of transmembrane receptors that activate the CheA kinase have been identified and overexpressed for crystallization with CheA. Resonance energy transfer and electron-spin interactions between CheA domains tagged with probes will correlate solution conformations to crystallographic structures and define limits of movement in the presence of receptor and CheW. Kinetic studies will interrogate CheA subunit exchange to determine its potential role in transmembrane signaling and response regulator activation. Our experiments will employ chemotaxis proteins from Thermatoga maritima, which due to their thermostability offer distinct advantages in crystallography, dynamical studies and kinetics. This work will lead to novel strategies for design of small molecules capable of modulating CheA activity. Given the absence of histidine kinases in eukaryotes and their essential role in bacterial virulence, they are ideal targets for a new class of antibiotics. Thus, we are also pursuing structure determinations of CheA from Helicobacter pylori, a known pathogen linked to ulcers and stomach cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TH1-TO TH2 SHIFT OF HSP65 RESPONSES AND ATHEROGENESIS Principal Investigator & Institution: Shibata, Yoshimi; Physiology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003

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Summary: (provided by applicant Infections caused by the intracellular organisms, Chlamydia pneumoniae, Mycobacterium sp. and/or Helicobacter pylori, have been implicated as co-risk factors in atherosclerosis, but their exact roles in disease progression remain controversial. We propose to characterize the immunological shifts in atherosclerosis that would be accelerated by the infections. Type 1 helper T lymphocyte- (Thl-) immunity activates local macrophages (MQ) that kill the intracellular bacteria and also potentially damage endothelial tissue, which could initiate lesions at the early stages. Previous studies suggest that splenic prostaglandin E2-releasing MQ (PGE2-MQ) levels are increased with the progression of atherosclerosis and in infections. Since PGE2 is a powerful inducer of the Thl to Th2 immune shift, PGE2-MQ could make a major contribution to the pathogenesis of chronic stages of atherosclerosis. In this. regard, much attention has been directed to mycobacterial 65kDa-heat shock protein (HSP65), an immunodominant antigen having cross-reactivity with other bacterial and mammalian HSPs. The Thl-to-Th2 shifts generate antibodies against HSP65 that potentially attack arteries through antigenic mimicry. Although the development of the Thl cells mediates resistance to tuberculosis, it remains unclear whether HSP65-specific Thl responses are also pro-atherogenic. Our goals are to understand the respective atherogenic roles of HSP65-specific Thl and Th2 responses as well as the mechanism of the shifts. We will employ hypercholesterolemic apolipoprotein E-knockout (apoE-KO) mice and wild type (WT) controls immunized with HSP65 or heat-killed (HK) M. bovis BCG containing HSP65. We hypothesize that HSP65-specific Th2 responses will enhance atherogenic lesion development in apoE-KO mice. We will determine if immunization with HSP65 and chitin, a Thl adjuvant, or alum, a Th2 adjuvant, will have an effect on atherogenic lesion development in apoE-KO mice. We will further determine if adoptive transfer of HSP65- specific Thl cells or Th2 cells will have an effect on atherogenic lesion development in apoE-KO recipients. Treatment of mice with 89Sr destroys PGE2-MQ precursors in the bone marrow and suppresses the formation of splenic PGE2-MG. We hypothesize that this will also result in retention of the Thl responses without a shift to a Th2 response. Mice treated with 89Srwill receive HK-BCG immunization to determine the effect on response to HSP65. Finally, we will determine if transfusion of fit-1 +marrow cells from HK-BCG treated WT donors will restore the Thl-to-Th2 shifts in 89Sr-treated WT recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UGI HEMORRHAGE AND BARRETTS EPITHELIUM Principal Investigator & Institution: Jensen, Dennis M.; Professor of Medicine; Ctr for Ulcer Research & Educ; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: My primary career goals related to this award are: 1) to pursue a program of investigator-initiated, hypothesis driven, high quality patient-oriented research in the specialty of digestive diseases, 2) to mentor young clinicians, with little or no research experience, in their career development as patient-oriented researchers, and 3) to continue to mentor and collaborate with other clinical researchers who are beyond the entry level as clinical investigators. Two NIH studies and several new collaborative studies support this research and mentoring proposal. The first NIH Grant, "Studies of UGI Hemorrhage and Endoscopic Hemostasis" evaluates patients with severe upper gastrointestinal bleeding (UGIB) from peptic ulcers, Dieulafoy's lesions, or Mallory Weiss tears. In three consecutive blinded, multicenter randomized trials, our hypothesis is that combination therapy (epinephrine and coagulation) will be significantly better

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than thermal therapy for initial hemostasis, reduction in early rebleeding rates, and reduction in hospital costs of care. The second NIH Grant, "Prevention of Ulcer Hemorrhage by H.pylori Eradication" is a multicenter, double-blind, randomized comparison of two different medical treatments to prevent recurrence of duodenal ulcer (DU) and gastric ulcer (GU) bleeding. The overall hypotheses to be tested are that 1) eradication of Helicobacter pylori (H. pylori) infection alone will cure most patients of their chronic peptic ulcers and will be substantially equivalent to H.pylori eradication plus full-dose H2RA maintenance in preventing recurrent ulcer hemorrhage and 2) ingestion of aspirin or other non-steroidal anti-inflammatory drugs or recurrence of H.pylori infection will account for all recurrences of ulcer hemorrhage during long-term follow-up. New collaborative studies are also proposed of Barrett's epithelium and prospective trials of variceal and non-variceal hemorrhage. In the mentoring program, new investigators will be trained to perform randomized prospective trials, endoscopic technology assessment studies, and patient-oriented research. This mentoring will be supplemented by didactic courses in biostatistics, seminars in study design, and other instruction in data management, form design for prospective trials, and protocol writing. Emphasis will be placed on planning, designing, and conducting actual prospective randomized studies. This award will enhance the applicant's research productivity and provide skilled mentoring for young investigators, so they can become independent patient-oriented investigators in digestive diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UREASE AND GENE EXPRESSION OF HELICOBACTER PYLORI Principal Investigator & Institution: Mobley, Harry L.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 30-JUN-2004 Summary: Helicobacter pylori, a gram-negative, microaerophilic spiral-shaped bacterium is the most frequently cited etiologic agent of human gastritis and peptic ulceration. This species, whose niche is highly restricted to the gastric mucosa of humans, has adopted a strategy of survival that includes synthesis of urease as its most abundant cellular protein. This enzyme hydrolyzes urea, releasing ammonia which allows colonization of this acid-sensitive organism at low gastric pH. In the previous funding period, we focused on factors that contribute to synthesis of a catalytically active urease. A rough topological model for the insertion of NixA, the high affinity nickel transport protein, into the cytoplasmic membrane has been established and we have identified 12 amino acid residues within the membrane domain that are critical for transport function. Three new urease-modulating factors including F1hA (flagellar biosynthesis/regulatory protein), Lpp (lipoprotein), and Hel (helicase) have been identified using a strategy similar to that used to isolate NixA. Glutamine synthetase which uses ammonia, the product of urea hydrolysis for production of glutamine from glutamate, has been characterized and demonstrated as essential for H. pylori survival. The role of Hpn, the histidine-rich protein, in bismuth sensitivity has also been elucidated. We postulate that NixA and other newly identified proteins are necessary for full activation of H. pylori urease. Since urea hydrolysis is 100 percent-dependent on nickel incorporation into urease, understanding this process could uncover targets for intervention. To address these research areas, we propose to use molecular genetic techniques, protein biochemistry, and bacterial physiology methodology: 1) To determine the mechanism by which urease activity is modulated. 2) To determine the fine structure of NixA, the mechanism of its gene regulation, and its contribution to

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virulence. 3) To determine the gene products that mediate transport of nickel ions across the inner and outer membranes of H. pylori. 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 “Helicobacter pylori” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Helicobacter pylori in the PubMed Central database: •

[gamma]-Glutamyltransferase Is a Helicobacter pylori Virulence Factor but Is Not Essential for Colonization. by McGovern KJ, Blanchard TG, Gutierrez JA, Czinn SJ, Krakowka S, Youngman P.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98487

•

13C-Urea breath test threshold calculation and evaluation for the detection of Helicobacter pylori infection in children. by Herold R, Becker M.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115843

•

15NH4+ excretion test: a new method for detection of Helicobacter pylori infection. by Wu JC, Liu GL, Zhang ZH, Mou YL, Chen QA, Wu JC, Yang SL.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265017

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16S rRNA Mutation-Mediated Tetracycline Resistance in Helicobacter pylori. by Gerrits MM, de Zoete MR, Arents NL, Kuipers EJ, Kusters JG.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127406

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A 12-Amino-Acid Segment, Present in Type s2 but Not Type s1 Helicobacter pylori VacA Proteins, Abolishes Cytotoxin Activity and Alters Membrane Channel Formation. by McClain MS, Cao P, Iwamoto H, Vinion-Dubiel AD, Szabo G, Shao Z, Cover TL.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95478

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A Conventional Beagle Dog Model for Acute and Chronic Infection with Helicobacter pylori. by Rossi G, Rossi M, Vitali CG, Fortuna D, Burroni D, Pancotto L, Capecchi S, Sozzi S, Renzoni G, Braca G, Del Giudice G, Rappuoli R, Ghiara P, Taccini E.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96629

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A Euthymic Hairless Mouse Model of Helicobacter pylori Colonization and Adherence to Gastric Epithelial Cells In Vivo. by Kimura N, Ariga M, Icatlo FC Jr, Kuroki M, Ohsugi M, Ikemori Y, Umeda K, Kodama Y.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95621

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A flagellar sheath protein of Helicobacter pylori is identical to HpaA, a putative Nacetylneuraminyllactose-binding hemagglutinin, but is not an adhesin for AGS cells. by Jones AC, Logan RP, Foynes S, Cockayne A, Wren BW, Penn CW.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179448

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A M r 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. by Yamaoka Y, Kwon DH, Graham DY.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16580

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A Novel Action of the Proton Pump Inhibitor Rabeprazole and Its Thioether Derivative against the Motility of Helicobacter pylori. by Tsutsui N, Taneike I, Ohara T, Goshi S, Kojio S, Iwakura N, Matsumaru H, Wakisaka-Saito N, Zhang HM, Yamamoto T.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101604

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A Novel Mechanism for Resistance to the Antimetabolite N-Phosphonoacetyl-lAspartate by Helicobacter pylori. by Burns BP, Mendz GL, Hazell SL.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107614

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A PCR-oligonucleotide ligation assay to determine the prevalence of 23S rRNA gene mutations in clarithromycin-resistant Helicobacter pylori. by Stone GG, Shortridge D, Versalovic J, Beyer J, Flamm RK, Graham DY, Ghoneim AT, Tanaka SK.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163779

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A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach. by Tsuda M, Karita M, Morshed MG, Okita K, Nakazawa T.; 1994 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303000

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A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. by Salama N, Guillemin K, McDaniel TK, Sherlock G, Tompkins L, Falkow S.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18976

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Accurate Prediction of Macrolide Resistance in Helicobacter pylori by a PCR Line Probe Assay for Detection of Mutations in the 23S rRNA Gene: Multicenter Validation Study. by van Doorn LJ, Glupczynski Y, Kusters JG, Megraud F, Midolo P, Maggi-Solca N, Queiroz DM, Nouhan N, Stet E, Quint WG.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90495

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Accurate, Noninvasive Detection of Helicobacter pylori DNA from Stool Samples: Potential Usefulness for Monitoring Treatment. by Shuber AP, Ascano JJ, Boynton KA, Mitchell A, Frierson HF Jr, El-Rifai W, Powell SM.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120120

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Acidic pH changes receptor binding specificity of Helicobacter pylori: a binary adhesion model in which surface heat shock (stress) proteins mediate sulfatide recognition in gastric colonization. by Huesca M, Borgia S, Hoffman P, Lingwood CA.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174121

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Activities of [beta]-Lactams and Macrolides against Helicobacter pylori. by Hassan IJ, Stark RM, Greenman J, Millar MR.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89284

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Adaptive mutation and cocolonization during Helicobacter pylori infection of gnotobiotic piglets. by Akopyants NS, Eaton KA, Berg DE.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172966

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Adherence of Isogenic Flagellum-Negative Mutants of Helicobacter pylori and Helicobacter mustelae to Human and Ferret Gastric Epithelial Cells. by Clyne M, Ocroinin T, Suerbaum S, Josenhans C, Drumm B.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101762

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Adoptive Transfer of CD4 + T Cells Specific for Subunit A of Helicobacter pylori Urease Reduces H. pylori Stomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling. by Lucas B, Bumann D, Walduck A, Koesling J, Develioglu L, Meyer TF, Aebischer T.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98077

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Age-Specific Helicobacter pylori Seropositivity Rates of Children in an Impoverished Urban Area of Northeast Brazil. by Mitchell A, Silva TM, Barrett LJ, Lima AA, Guerrant RL.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150276

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Allelic Diversity of the Helicobacter pylori Vacuolating Cytotoxin Gene in South Africa: Rarity of the vacA s1a Genotype and Natural Occurrence of an s2/m1 Allele. by Letley DP, Lastovica A, Louw JA, Hawkey CJ, Atherton JC.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88677

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Allelic exchange mutagenesis of nixA in Helicobacter pylori results in reduced nickel transport and urease activity. by Bauerfeind P, Garner RM, Mobley LT.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174160

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Allelic Variation within Helicobacter pylori babA and babB. by Pride DT, Meinersmann RJ, Blaser MJ.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97998

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Alterations in Penicillin-Binding Protein 1A Confer Resistance to [beta]-Lactam Antibiotics in Helicobacter pylori. by Gerrits MM, Schuijffel D, van Zwet AA, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127293

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Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. by Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, Sato F, Kato T, Kohli Y, Kuriyama M.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229827

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Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. by Xiang Z, Censini S, Bayeli PF, Telford JL, Figura N, Rappuoli R, Covacci A.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172962

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Analysis of F1F0-ATPase from Helicobacter pylori. by McGowan CC, Cover TL, Blaser MJ.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175373

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Analysis of rdxA and Involvement of Additional Genes Encoding NAD(P)H Flavin Oxidoreductase (FrxA) and Ferredoxin-Like Protein (FdxB) in Metronidazole Resistance of Helicobacter pylori. by Kwon DH, El-Zaatari FA, Kato M, Osato MS, Reddy R, Yamaoka Y, Graham DY.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90025

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Analysis of vacA, cagA, and IS605 Genotypes and Those Determined by PCR Amplification of DNA between Repetitive Sequences of Helicobacter pylori Strains Isolated from Patients with Nonulcer Dyspepsia or Mucosa-Associated Lymphoid Tissue Lymphoma. by van Doorn NE, Namavar F, van Doorn LJ, Durrani Z, Kuipers EJ, Vandenbroucke-Grauls CM.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85157

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Another Unusual Type of Citric Acid Cycle Enzyme in Helicobacter pylori: the Malate:Quinone Oxidoreductase. by Kather B, Stingl K, van der Rest ME, Altendorf K, Molenaar D.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94508

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Antibiotic Resistance of Helicobacter pylori Strains in Japanese Children. by Kato S, Fujimura S, Udagawa H, Shimizu T, Maisawa S, Ozawa K, Iinuma K.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153406

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Antibody to Heat Shock Protein Can Be Used for Early Serological Monitoring of Helicobacter pylori Eradication Treatment. by Yunoki N, Yokota K, Mizuno M, Kawahara Y, Adachi M, Okada H, Hayashi S, Hirai Y, Oguma K, Tsuji T.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95916

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Antimicrobial Susceptibilities of Helicobacter pylori Isolates under Microaerophilic Atmospheres Established by Two Different Methods. by Kobayashi I, Muraoka H, Saika T, Nishida M, Fujioka T, Nasu M.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88201

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Antimicrobial Susceptibility of Helicobacter pylori Determined by the E Test Using Tetrazolium Egg Yolk Agar. by Valdez Y, Velapatino B, Gilman RH, Gutierrez V, Leon C.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105210

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Antimicrobial susceptibility testing of 230 Helicobacter pylori strains: importance of medium, inoculum, and incubation time. by Hartzen SH, Andersen LP, Bremmelgaard A, Colding H, Arpi M, Kristiansen J, Justesen T, Espersen F, Frimodt-Moller N, Bonnevie O.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164182

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Antimicrobial Susceptibility Testing of Helicobacter pylori in a Large Multicenter Trial: the MACH 2 Study. by Megraud F, Lehn N, Lind T, Bayerdorffer E, O'Morain C, Spiller R, Unge P, van Zanten SV, Wrangstadh M, Burman CF.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89554

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Antimicrobial Therapies for Helicobacter pylori Infection in Gnotobiotic Piglets. by Krakowka S, Eaton KA, Leunk RD.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105643

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Antrum- and Corpus Mucosa-Infiltrating CD4 + Lymphocytes in Helicobacter pylori Gastritis Display a Th1 Phenotype. by Sommer F, Faller G, Konturek P, Kirchner T, Hahn EG, Zeus J, Rollinghoff M, Lohoff M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108696

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Assessment of Clarithromycin-Resistant Helicobacter pylori among Patients in Shanghai and Guangzhou, China, by Primer-Mismatch PCR. by Pan ZJ, Su WW, Tytgat GN, Dankert J, van der Ende A.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120094

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Assessment of Helicobacter pylori Gene Expression within Mouse and Human Gastric Mucosae by Real-Time Reverse Transcriptase PCR. by Rokbi B, Seguin D, Guy B, Mazarin V, Vidor E, Mion F, Cadoz M, Quentin-Millet MJ.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98562

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Assessment of Helicobacter pylori vacA and cagA Genotypes and Host Serological Response. by Figueiredo C, Quint W, Nouhan N, van den Munckhof H, Herbrink P, Scherpenisse J, de Boer W, Schneeberger P, Perez-Perez G, Blaser MJ, van Doorn LJ.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87936

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Association of cagA and vacA Genotypes of Helicobacter pylori with Gastric Diseases in Estonia. by Andreson H, Loivukene K, Sillakivi T, Maaroos HI, Ustav M, Peetsalu A, Mikelsaar M.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120128

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Association of Helicobacter pylori Antioxidant Activities with Host Colonization Proficiency. by Olczak AA, Seyler, Jr. RW, Olson JW, Maier RJ.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143418

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Association of Metronidazole Resistance and Natural Competence in Helicobacter pylori. by Yeh YC, Chang KC, Yang JC, Fang CT, Wang JT.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127164

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Attenuated Salmonella enterica Serovar Typhi Expressing Urease Effectively Immunizes Mice against Helicobacter pylori Challenge as Part of a Heterologous Mucosal Priming-Parenteral Boosting Vaccination Regimen. by Londono-Arcila P, Freeman D, Kleanthous H, O'Dowd AM, Lewis S, Turner AK, Rees EL, Tibbitts TJ, Greenwood J, Monath TP, Darsley MJ.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128259

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babA2- and cagA-Positive Helicobacter pylori Strains Are Associated with Duodenal Ulcer and Gastric Carcinoma in Brazil. by Oliveira AG, Santos A, Guerra JB, Rocha GA, Rocha AM, Oliveira CA, Cabral MM, Nogueira AM, Queiroz DM.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179833

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Bacterial activity of a new antiulcer agent, ecabet sodium, against Helicobacter pylori under acidic conditions. by Shibata K, Ito Y, Hongo A, Yasoshima A, Endo T, Ohashi M.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162730

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Bactericidal and morphological effects of amoxicillin on Helicobacter pylori. by Berry V, Jennings K, Woodnutt G.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162840

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Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. by Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137900

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Bisulfite or sulfite inhibits growth of Helicobacter pylori. by Hawrylik SJ, Wasilko DJ, Haskell SL, Gootz TD, Lee SE.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263125

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Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. by Guillemin K, Salama NR, Tompkins LS, Falkow S.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137556

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cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and diseaseassociated virulence factors. by Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26189

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cagA and vacA in strains of Helicobacter pylori from ulcer and non-ulcerative dyspepsia patients. by Faundez G, Troncoso M, Figueroa G.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128829

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cagA and vacA Status of Spanish Helicobacter pylori Clinical Isolates. by Domingo D, Alarcon T, Prieto N, Sanchez I, Lopez-Brea M.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85056

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cagA Status and Eradication Treatment Outcome of Anti-Helicobacter pylori Triple Therapies in Patients with Nonulcer Dyspepsia. by Broutet N, Marais A, Lamouliatte H, de Mascarel A, Samoyeau R, Salamon R, Megraud F.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87932

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cagA-Positive Helicobacter pylori Populations in China and The Netherlands Are Distinct. by van der Ende A, Pan ZJ, Bart A, van der Hulst RW, Feller M, Xiao SD, Tytgat GN, Dankert J.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108130

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Categorization of clinical isolates of Helicobacter pylori on the basis of restriction digest analyses of polymerase chain reaction-amplified ureC genes. by Moore RA, Kureishi A, Wong S, Bryan LE.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262931

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cDNA Array Analysis of cag Pathogenicity Island-Associated Helicobacter pylori Epithelial Cell Response Genes. by Cox JM, Clayton CL, Tomita T, Wallace DM, Robinson PA, Crabtree JE.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100077

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Cell Specificity of Helicobacter pylori Cytotoxin Is Determined by a Short Region in the Polymorphic Midregion. by Ji X, Fernandez T, Burroni D, Pagliaccia C, Atherton JC, Reyrat JM, Rappuoli R, Telford JL.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97673

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Changes in Helicobacter pylori ultrastructure and antigens during conversion from the bacillary to the coccoid form. by Benaissa M, Babin P, Quellard N, Pezennec L, Cenatiempo Y, Fauchere JL.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174074

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Characteristics of Helicobacter pylori Infection in Jamaican Adults with Gastrointestinal Symptoms. by Hisada M, Lee MG, Hanchard B, Owens M, Song Q, van Doorn LJ, Cutler AF, Gold BD.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87704

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Characteristics of Helicobacter pylori variants selected for urease deficiency. by PerezPerez GI, Olivares AZ, Cover TL, Blaser MJ.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257374

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Characterization and Immunogenicity of the CagF Protein of the cag Pathogenicity Island of Helicobacter pylori. by Seydel A, Tasca E, Berti D, Rappuoli R, Del Giudice G, Montecucco C.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130411

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Characterization and presumptive identification of Helicobacter pylori isolates from rhesus monkeys. by Drazek ES, Dubois A, Holmes RK.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263799

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Characterization of a ComE3 Homologue Essential for DNA Transformation in Helicobacter pylori. by Yeh YC, Lin TL, Chang KC, Wang JT.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187363

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Characterization of an In Vitro-Selected Amoxicillin-Resistant Strain of Helicobacter pylori. by DeLoney CR, Schiller NL.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90207

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Characterization of chromosomal DNA profiles from Helicobacter pylori strains isolated from sequential gastric biopsy specimens. by Salama SM, Jiang Q, Chang N, Sherbaniuk RW, Taylor DE.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228454

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Characterization of feline Helicobacter pylori strains and associated gastritis in a colony of domestic cats. by Handt LK, Fox JG, Stalis IH, Rufo R, Lee G, Linn J, Li X, Kleanthous H.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228395

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Characterization of the HspR-Mediated Stress Response in Helicobacter pylori. by Spohn G, Delany I, Rappuoli R, Scarlato V.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135076

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Clarifications Regarding the 3[prime prime or minute] Repeat Region of the cagA Gene in Helicobacter pylori and Clinical Outcome. by Yamaoka Y, Graham DY.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88152

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Clarithromycin Resistance among Helicobacter pylori Strains Isolated from Children: Prevalence and Study of Mechanism of Resistance by PCR-Restriction Fragment Length Polymorphism Analysis. by Alarcon T, Vega AE, Domingo D, Martinez MJ, Lopez-Brea M.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149579

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Clarithromycin-Susceptible and -Resistant Helicobacter pylori Isolates with Identical Randomly Amplified Polymorphic DNA-PCR Genotypes Cultured from Single

130

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Gastric Biopsy Specimens Prior to Antibiotic Therapy. by van der Ende A, van Doorn LJ, Rooijakkers S, Feller M, Tytgat GN, Dankert J.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88202 •

Clearance of Helicobacter pylori Infection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice. by Garhart CA, Redline RW, Nedrud JG, Czinn SJ.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128038

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Clinical Relevance of the babA2 Genotype of Helicobacter pylori in Japanese Clinical Isolates. by Mizushima T, Sugiyama T, Komatsu Y, Ishizuka J, Kato M, Asaka M.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88171

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Cloning and Characterization of a Novel Membrane-Associated Antigenic Protein of Helicobacter pylori. by Yoshida M, Wakatsuki Y, Kobayashi Y, Itoh T, Murakami K, Mizoguchi A, Usui T, Chiba T, Kita T.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96309

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Cloning and characterization of hemolytic genes from Helicobacter pylori. by Drazek ES, Dubois A, Holmes RK, Kersulyte D, Akopyants NS, Berg DE, Warren RL.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173618

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Cloning and characterization of the Helicobacter pylori flbA gene, which codes for a membrane protein involved in coordinated expression of flagellar genes. by Schmitz A, Josenhans C, Suerbaum S.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178789

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Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain. by Odenbreit S, Wieland B, Haas R.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178599

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Cloning and sequence analysis of two copies of a 23S rRNA gene from Helicobacter pylori and association of clarithromycin resistance with 23S rRNA mutations. by Taylor DE, Ge Z, Purych D, Lo T, Hiratsuka K.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164180

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Cluster of Type IV Secretion Genes in Helicobacter pylori's Plasticity Zone. by Kersulyte D, Velapatino B, Mukhopadhyay AK, Cahuayme L, Bussalleu A, Combe J, Gilman RH, Berg DE.; 2003 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161572

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Clustering of Clinical Strains of Helicobacter pylori Analyzed by Two-Dimensional Gel Electrophoresis. by Enroth H, Akerlund T, Sillen A, Engstrand L.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95866

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Clustering of South African Helicobacter pylori Isolates from Peptic Ulcer Disease Patients Is Demonstrated by Repetitive Extragenic Palindromic-PCR Fingerprinting. by Kidd M, Atherton JC, Lastovica AJ, Louw JA.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88034

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Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to gastric epithelial cells and induce interleukin-8 secretion. by Cole SP, Cirillo D, Kagnoff MF, Guiney DG, Eckmann L.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176138

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Coccoid forms of Helicobacter pylori are the morphologic manifestation of cell death. by Kusters JG, Gerrits MM, Van Strijp JA, Vandenbroucke-Grauls CM.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175523

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Colonization of C57BL/6J and BALB/c Wild-Type and Knockout Mice with Helicobacter pylori: Effect of Vaccination and Implications for Innate and Acquired Immunity. by Panthel K, Faller G, Haas R.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145401

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Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. by Eaton KA, Suerbaum S, Josenhans C, Krakowka S.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174096

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Colonization of Mexican Patients by Multiple Helicobacter pylori Strains with Different vacA and cagA Genotypes. by Morales-Espinosa R, Castillo-Rojas G, Gonzalez-Valencia G, Ponce de Leon S, Cravioto A, Atherton JC, Lopez-Vidal Y.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85434

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Comparative Genomics of Helicobacter pylori: Analysis of the Outer Membrane Protein Families. by Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101716

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Comparative ultrastructural and functional studies of Helicobacter pylori and Helicobacter mustelae flagellin mutants: both flagellin subunits, FlaA and FlaB, are necessary for full motility in Helicobacter species. by Josenhans C, Labigne A, Suerbaum S.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176987

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Comparison of Fluorescent In Situ Hybridization and Conventional Culturing for Detection of Helicobacter pylori in Gastric Biopsy Specimens. by Russmann H, Kempf VA, Koletzko S, Heesemann J, Autenrieth IB.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87719

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Comparison of Four Serological Tests To Determine the CagA or VacA Status of Helicobacter pylori Strains. by Yamaoka Y, Kodama T, Graham DY, Kashima K.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105352

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Comparison of Genetic Divergence and Fitness between Two Subclones of Helicobacter pylori. by Bjorkholm B, Lundin A, Sillen A, Guillemin K, Salama N, Rubio C, Gordon JI, Falk P, Engstrand L.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98879

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Comparison of Genomic Structures and Antigenic Reactivities of Orthologous 29Kilodalton Outer Membrane Proteins of Helicobacter pylori. by Sumie A, Yamashiro T, Nakashima K, Nasu M, Watanabe M, Nishizono A.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100063

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Comparison of Genotyping Helicobacter pylori Directly from Biopsy Specimens and Genotyping from Bacterial Cultures. by Park CY, Kwak M, Gutierrez O, Graham DY, Yamaoka Y.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165374

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Comparison of new faecal antigen test with 13C-urea breath test for detecting Helicobacter pylori infection and monitoring eradication treatment: prospective clinical evaluation. by Braden B, Teuber G, Dietrich CF, Caspary WF, Lembcke B.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27260

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Comparison of PCR-based restriction length polymorphism analysis of urease genes with rRNA gene profiling for monitoring Helicobacter pylori infections in patients on triple therapy. by Owen RJ, Bickley J, Hurtado A, Fraser A, Pounder RE.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263645

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Comparison of PCR-Restriction Fragment Length Polymorphism Analysis and PCRDirect Sequencing Methods for Differentiating Helicobacter pylori ureB Gene Variants. by Tanahashi T, Kita M, Kodama T, Sawai N, Yamaoka Y, Mitsufuji S, Katoh F, Imanishi J.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86046

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Comparison of the nucleic acids of helical and coccoid forms of Helicobacter pylori. by Narikawa S, Kawai S, Aoshima H, Kawamata O, Kawaguchi R, Hikiji K, Kato M, Iino S, Mizushima Y.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170520

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Comparison of three commercially available enzyme-linked immunosorbent assays and biopsy-dependent diagnosis for detecting Helicobacter pylori infection. by van de Wouw BA, de Boer WA, Jansz AR, Roymans RT, Staals AP.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228738

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Comparison of Two Rapid Whole-Blood Tests for Helicobacter pylori Infection in Chinese Patients. by Leung WK, Chan FK, Falk MS, Suen R, Sung JJ.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105355

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Competition of Various [beta]-Lactam Antibiotics for the Major Penicillin-Binding Proteins of Helicobacter pylori: Antibacterial Activity and Effects on Bacterial Morphology. by DeLoney CR, Schiller NL.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89546

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Composition and Gene Expression of the cag Pathogenicity Island in Helicobacter pylori Strains Isolated from Gastric Carcinoma and Gastritis Patients in Costa Rica. by Occhialini A, Marais A, Urdaci M, Sierra R, Munoz N, Covacci A, Megraud F.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98100

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Consensus and Variable Region PCR Analysis of Helicobacter pylori 3[prime prime or minute] Region of cagA Gene in Isolates from Individuals with or without Peptic Ulcer. by Rota CA, Pereira-Lima JC, Blaya C, Nardi NB.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87784

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Construction of a Helicobacter pylori-Escherichia coli shuttle vector for gene transfer in Helicobacter pylori. by Lee WK, An YS, Kim KH, Kim SH, Song JY, Ryu BD, Choi YJ, Yoon YH, Baik SC, Rhee KH, Cho MJ.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168813

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Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. by Cover TL, Cao P, Lind CD, Tham KT, Blaser MJ.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281276

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Culture of Helicobacter pylori from a Gastric String May Be an Alternative to Endoscopic Biopsy. by Samuels AL, Windsor HM, Ho GY, Goodwin LD, Marshall BJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86836

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Cure of Helicobacter pylori Infection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice. by Eaton KA, Mefford ME.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97983

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Cytotoxin production by Helicobacter pylori from patients with upper gastrointestinal tract diseases. by Tee W, Lambert JR, Dwyer B.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228131

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Dependence of Helicobacter pylori Urease Activity on the Nickel-Sequestering Ability of the UreE Accessory Protein. by Benoit S, Maier RJ.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166491

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Detection of Anti-VacA Antibody Responses in Serum and Gastric Juice Samples Using Type s1/m1 and s2/m2 Helicobacter pylori VacA Antigens. by Perez-Perez GI, Peek RM Jr, Atherton JC, Blaser MJ, Cover TL.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95713

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Detection of Chlamydia pneumoniae and Helicobacter pylori DNA in Human Atherosclerotic Plaques by PCR. by Farsak B, Yildirir A, Akyon Y, Pinar A, Oc M, Boke E, Kes S, Tokgozoglu L.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87613

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Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. by Blasi F, Denti F, Erba M, Cosentini R, Raccanelli R, Rinaldi A, Fagetti L, Esposito G, Ruberti U, Allegra L.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229401

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Detection of Clarithromycin-Resistant Helicobacter pylori in Stool Samples. by Fontana C, Favaro M, Pietroiusti A, Pistoia ES, Galante A, Favalli C.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179782

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Detection of Clarithromycin-Resistant Helicobacter pylori Strains by a Preferential Homoduplex Formation Assay. by Maeda S, Yoshida H, Matsunaga H, Ogura K, Kawamata O, Shiratori Y, Omata M.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88697

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Detection of Helicobacter pylori DNA in Fecal Samples from Infected Individuals. by Gramley WA, Asghar A, Frierson HF Jr, Powell SM.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85126

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Detection of Helicobacter pylori gene expression in human gastric mucosa. by Peek RM Jr, Miller GG, Tham KT, Perez-Perez GI, Cover TL, Atherton JC, Dunn GD, Blaser MJ.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227873

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Detection of Helicobacter pylori in Gastric Mucosa of Patients with Gastroduodenal Diseases by PCR-Restriction Analysis Using the RNA Polymerase Gene (rpoB). by Lim CY, Lee KH, Cho MJ, Chang MW, Kim SY, Myong NH, Lee WK, Rhee KH, Kook YH.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165300

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Detection of Helicobacter pylori in Paraffin-Embedded and in Shock-Frozen Gastric Biopsy Samples by Fluorescent In Situ Hybridization. by Russmann H, Feydt-Schmidt A, Adler K, Aust D, Fischer A, Koletzko S.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149697

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Detection of Point Mutations Associated with Resistance of Helicobacter pylori to Clarithromycin by Hybridization in Liquid Phase. by Pina M, Occhialini A, Monteiro L, Doermann HP, Megraud F.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105316

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Determination of Helicobacter pylori Virulence by Simple Gene Analysis of the cag Pathogenicity Island. by Ikenoue T, Maeda S, Ogura K, Akanuma M, Mitsuno Y, Imai Y, Yoshida H, Shiratori Y, Omata M.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96031

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Determination of Redundancy and Systems Properties of the Metabolic Network of Helicobacter pylori Using Genome-Scale Extreme Pathway Analysis. by Price ND, Papin JA, Palsson BO.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=186586

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Determination of the Infectious Dose of Helicobacter pylori during Primary and Secondary Infection in Rhesus Monkeys (Macaca mulatta). by Solnick JV, Hansen LM, Canfield DR, Parsonnet J.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100068

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Development of a Plating Medium for Selection of Helicobacter pylori from Water Samples. by Degnan AJ, Sonzogni WC, Standridge JH.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154490

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Development of a Scheme for Genotyping Helicobacter pylori Based on Allelic Variation in Urease Subunit Genes. by Owen RJ, Slater ER, Xerry J, Peters TM, Teare EL, Grant A.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105271

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Development of a Selective Medium for Isolation of Helicobacter pylori from Cattle and Beef Samples. by Stevenson TH, Lucia LM, Acuff GR.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91887

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Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens. by Lage AP, Godfroid E, Fauconnier A, Burette A, Butzler JP, Bollen A, Glupczynski Y.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228568

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Diagnosis of Helicobacter pylori Infection in Children: Comparison of a Salivary Immunoglobulin G Antibody Test with the [13C]Urea Breath Test. by Bode G, Marchildon P, Peacock J, Brenner H, Rothenbacher D.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119956

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Differences in Genotypes of Helicobacter pylori from Different Human Populations. by Kersulyte D, Mukhopadhyay AK, Velapatino B, Su W, Pan Z, Garcia C, Hernandez V, Valdez Y, Mistry RS, Gilman RH, Yuan Y, Gao H, Alarcon T, Lopez-Brea M, Balakrish Nair G, Chowdhury A, Datta S, Shirai M, Nakazawa T, Ally R, Segal I, Wong BC, Lam SK, Olfat FO, Boren T, Engstrand L, Torres O, Schneider R, Thomas JE, Czinn S, Berg DE.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94509

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Differences in Surface-Exposed Antigen Expression between Helicobacter pylori Strains Isolated from Duodenal Ulcer Patients and from Asymptomatic Subjects. by Thoreson AC, Hamlet A, Celik J, Bystrom M, Nystrom S, Olbe L, Svennerholm AM.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87400

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Differential Gene Expression from Two Transcriptional Units in the cag Pathogenicity Island of Helicobacter pylori. by Joyce EA, Gilbert JV, Eaton KA, Plaut A, Wright A.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98452

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Differentiation of Helicobacter pylori Isolates Based on Lectin Binding of Cell Extracts in an Agglutination Assay. by Hynes SO, Hirmo S, Wadstrom T, Moran AP.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85005

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Differentiation of Helicobacter pylori strains directly from gastric biopsy specimens by PCR-based restriction fragment length polymorphism analysis without culture. by Li C, Ha T, Chi DS, Ferguson DA Jr, Jiang C, Laffan JJ, Thomas E.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230115

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Differentiation of Metronidazole-Sensitive and -Resistant Clinical Isolates of Helicobacter pylori by Immunoblotting with Antisera to the RdxA Protein. by Latham SR, Owen RJ, Elviss NC, Labigne A, Jenks PJ.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88295

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Direct Detection of Helicobacter pylori Mutations Associated with Macrolide Resistance in Gastric Biopsy Material Taken from Human Immunodeficiency VirusInfected Subjects. by Scarpellini P, Carrera P, Cavallero A, Cernuschi M, Mezzi G, Testoni PA, Zingale A, Lazzarin A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130724

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Direct Evidence by DNA Fingerprinting that Endoscopic Cross-Infection of Helicobacter pylori Is a Cause of Postendoscopic Acute Gastritis. by Sugiyama T, Naka H, Yachi A, Asaka M.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86812

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Distinct Variants of Helicobacter pylori cagA Are Associated with vacA Subtypes. by van Doorn LJ, Figueiredo C, Sanna R, Blaser MJ, Quint WG.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85143

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Distinctiveness of Genotypes of Helicobacter pylori in Calcutta, India. by Mukhopadhyay AK, Kersulyte D, Jeong JY, Datta S, Ito Y, Chowdhury A, Chowdhury S, Santra A, Bhattacharya SK, Azuma T, Nair GB, Berg DE.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94510

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Diversity among Helicobacter pylori isolates. by Taylor DE.; 1996 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=228951

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Diversity in Protein Synthesis and Viability of Helicobacter pylori Coccoid Forms in Response to Various Stimuli. by Mizoguchi H, Fujioka T, Kishi K, Nishizono A, Kodama R, Nasu M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108699

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Diversity of Helicobacter pylori vacA and cagA Genes and Relationship to VacA and CagA Protein Expression, Cytotoxin Production, and Associated Diseases. by Rudi J, Kolb C, Maiwald M, Kuck D, Sieg A, Galle PR, Stremmel W.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104665

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DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD fingerprinting. by Akopyanz N, Bukanov NO, Westblom TU, Kresovich S, Berg DE.; 1992 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334296

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DNA Fingerprinting of Single Colonies of Helicobacter pylori from Gastric Cancer Patients Suggests Infection with a Single Predominant Strain. by Miehlke S, Thomas R, Guiterrez O, Graham DY, Go MF.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84224

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DNA Sequence Analysis of rdxA and frxA from 12 Pairs of Metronidazole-Sensitive and -Resistant Clinical Helicobacter pylori Isolates. by Kwon DH, Hulten K, Kato M, Kim JJ, Lee M, El-Zaatari FA, Osato MS, Graham DY.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90700

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DNA-Level Characterization of Helicobacter pylori Strains from Patients with Overt Disease and with Benign Infections in Bangladesh. by Rahman M, Mukhopadhyay AK, Nahar S, Datta S, Mashhud Ahmad M, Sarker S, Masud IM, Engstrand L, Albert MJ, Nair GB, Berg DE.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154730

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East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage. by Ghose C, Perez-Perez GI, Dominguez-Bello MG, Pride DT, Bravi CM, Blaser MJ.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137551

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Effect of Cold Starvation, Acid Stress, and Nutrients on Metabolic Activity of Helicobacter pylori. by Nilsson HO, Blom J, Al-Soud WA, Ljungh A, Andersen LP, Wadstrom T.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126563

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Effect of growth phase and acid shock on Helicobacter pylori cagA expression. by Karita M, Tummuru MK, Wirth HP, Blaser MJ.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174404

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Effect of Helicobacter pylori on gastric epithelial cell migration and proliferation in vitro: role of VacA and CagA. by Ricci V, Ciacci C, Zarrilli R, Sommi P, Tummuru MK, Del Vecchio Blanco C, Bruni CB, Cover TL, Blaser MJ, Romano M.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174149

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Effect of Helicobacter pylori on Polymorphonuclear Leukocyte Migration across Polarized T84 Epithelial Cell Monolayers: Role of Vacuolating Toxin VacA and cag Pathogenicity Island. by Hofman V, Ricci V, Galmiche A, Brest P, Auberger P, Rossi B, Boquet P, Hofman P.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101782

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Effect of Oxidizing Disinfectants (Chlorine, Monochloramine, and Ozone) on Helicobacter pylori. by Baker KH, Hegarty JP, Redmond B, Reed NA, Herson DS.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126689

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Effect of Rebamipide, a Novel Antiulcer Agent, on Helicobacter pylori Adhesion to Gastric Epithelial Cells. by Hayashi S, Sugiyama T, Amano KI, Isogai H, Isogai E, Aihara M, Kikuchi M, Asaka M, Yokota K, Oguma K, Fujii N, Hirai Y.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105706

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Effect of Weissella confusa Strain PL9001 on the Adherence and Growth of Helicobacter pylori. by Nam H, Ha M, Bae O, Lee Y.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124069

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Effects of 16S rRNA Gene Mutations on Tetracycline Resistance in Helicobacter pylori. by Gerrits MM, Berning M, Van Vliet AH, Kuipers EJ, Kusters JG.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182601

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Emergence of Tetracycline Resistance in Helicobacter pylori: Multiple Mutational Changes in 16S Ribosomal DNA and Other Genetic Loci. by Dailidiene D, Bertoli MT, Miciuleviciene J, Mukhopadhyay AK, Dailide G, Pascasio MA, Kupcinskas L, Berg DE.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132778

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Energetics of Helicobacter pylori and Its Implications for the Mechanism of UreaseDependent Acid Tolerance at pH 1. by Stingl K, Uhlemann EM, Schmid R, Altendorf K, Bakker EP.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135060

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Enzymes Associated with Reductive Activation and Action of Nitazoxanide, Nitrofurans, and Metronidazole in Helicobacter pylori. by Sisson G, Goodwin A, Raudonikiene A, Hughes NJ, Mukhopadhyay AK, Berg DE, Hoffman PS.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127316

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Enzymology of Type IV Macromolecule Secretion Systems: the Conjugative Transfer Regions of Plasmids RP4 and R388 and the cag Pathogenicity Island of Helicobacter pylori Encode Structurally and Functionally Related Nucleoside Triphosphate Hydrolases. by Krause S, Pansegrau W, Lurz R, de la Cruz F, Lanka E.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101984

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Epithelial Intestinal Cell Apoptosis Induced by Helicobacter pylori Depends on Expression of the cag Pathogenicity Island Phenotype. by Le'Negrate G, Ricci V, Hofman V, Mograbi B, Hofman P, Rossi B.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98593

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Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia. by Pan ZJ, van der Hulst RW, Feller M, Xiao SD, Tytgat GN, Dankert J, van der Ende A.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229746

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Essential Role of Ferritin Pfr in Helicobacter pylori Iron Metabolism and Gastric Colonization. by Waidner B, Greiner S, Odenbreit S, Kavermann H, Velayudhan J, Stahler F, Guhl J, Bisse E, van Vliet AH, Andrews SC, Kusters JG, Kelly DJ, Haas R, Kist M, Bereswill S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128114

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Essential Thioredoxin-Dependent Peroxiredoxin System from Helicobacter pylori: Genetic and Kinetic Characterization. by Baker LM, Raudonikiene A, Hoffman PS, Poole LB.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95091

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Evaluation of 16S rRNA Gene PCR with Primers Hp1 and Hp2 for Detection of Helicobacter pylori. by Leung WK.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104590

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Evaluation of 16S rRNA gene PCR with primers Hp1 and Hp2 for detection of Helicobacter pylori. by Chong SK, Lou Q, Fitzgerald JF, Lee CH.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229394

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Evaluation of a Novel Heminested PCR Assay Based on the Phosphoglucosamine Mutase Gene for Detection of Helicobacter pylori in Saliva and Dental Plaque. by Goosen C, Theron J, Ntsala M, Maree FF, Olckers A, Botha SJ, Lastovica AJ, van der Merwe SW.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120087

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Evaluation of a PCR Primer Based on the Isocitrate Dehydrogenase Gene for Detection of Helicobacter pylori in Feces. by Argyros FC, Ghosh M, Huang L, Masubuchi N, Cave DR, Grubel P.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87470

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Evaluation of a Selective Transport Medium for Gastric Biopsy Specimens To Be Cultured for Helicobacter pylori. by Siu LK, Leung WK, Cheng AF, Sung JY, Ling TK, Ling JM, Ng EK, Lau JY, Chung SC.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105110

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Evaluation of Clarithromycin Resistance and cagA and vacA Genotyping of Helicobacter pylori Strains from the West of Ireland Using Line Probe Assays. by Ryan KA, van Doorn LJ, Moran AP, Glennon M, Smith T, Maher M.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88063

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Evaluation of Commercially Available Helicobacter pylori Serology Kits: a Review. by Laheij RJ, Straatman H, Jansen JB, Verbeek AL.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105068

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Evaluation of eight enzyme immunoassays for detection of immunoglobulin G against Helicobacter pylori. by Meijer BC, Thijs JC, Kleibeuker JH, van Zwet AA, Berrelkamp RJ.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229561

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Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and Resistant Helicobacter pylori Infections in Mice. by Jenks PJ, Ferrero RL, Tankovic J, Thiberge JM, Labigne A.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90126

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Evaluation of performances of three DNA enzyme immunoassays for detection of Helicobacter pylori PCR products from biopsy specimens. by Monteiro L, Cabrita J, Megraud F.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230090

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Evaluation of the Effects of Strain-Specific Antigen Variation on the Accuracy of Serologic Diagnosis of Helicobacter pylori Infection. by Marchildon PA, Sugiyama T, Fukada Y, Peacock JS, Asaka M, Shimoyama T, Graham DY.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153909

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Evidence for a Signaling System in Helicobacter pylori: Detection of a luxS-Encoded Autoinducer. by Joyce EA, Bassler BL, Wright A.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94532

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Evidence for ethnic tropism of Helicobacter pylori. by Campbell S, Fraser A, Holliss B, Schmid J, O'Toole PW.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175528

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Evidence for Specific Secretion Rather than Autolysis in the Release of Some Helicobacter pylori Proteins. by Vanet A, Labigne A.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108011

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Evidence from a Nine-Year Birth Cohort Study in Japan of Transmission Pathways of Helicobacter pylori Infection. by Malaty HM, Kumagai T, Tanaka E, Ota H, Kiyosawa K, Graham DY, Katsuyama T.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86638

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Expanding Allelic Diversity of Helicobacter pylori vacA. by van Doorn LJ, Figueiredo C, Sanna R, Pena S, Midolo P, Ng EK, Atherton JC, Blaser MJ, Quint WG.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105169

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Experimental Infection of Mongolian Gerbils with Wild-Type and Mutant Helicobacter pylori Strains. by Wirth HP, Beins MH, Yang M, Tham KT, Blaser MJ.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108601

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Explaining the Bias in the 23S rRNA Gene Mutations Associated with Clarithromycin Resistance in Clinical Isolates of Helicobacter pylori. by Debets-Ossenkopp YJ, Brinkman AB, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105932

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Exposure to Metronidazole In Vivo Readily Induces Resistance in Helicobacter pylori and Reduces the Efficacy of Eradication Therapy in Mice. by Jenks PJ, Labigne A, Ferrero RL.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89206

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Expression of Helicobacter pylori Vacuolating Toxin in Escherichia coli. by McClain MS, Cover TL.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152094

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Expression of Surfactant Protein D in the Human Gastric Mucosa and during Helicobacter pylori Infection. by Murray E, Khamri W, Walker MM, Eggleton P, Moran AP, Ferris JA, Knapp S, Karim QN, Worku M, Strong P, Reid KB, Thursz MR.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127735

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Expression of the Helicobacter pylori ureI Gene Is Required for Acidic pH Activation of Cytoplasmic Urease. by Scott DR, Marcus EA, Weeks DL, Lee A, Melchers K, Sachs G.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97165

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Expression of the human cell surface glycoconjugates Lewis x and Lewis y by Helicobacter pylori isolates is related to cagA status. by Wirth HP, Yang M, Karita M, Blaser MJ.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174419

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Extracellular Release of Antigenic Proteins by Helicobacter pylori. by Cao P, McClain MS, Forsyth MH, Cover TL.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108299

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Factors affecting growth and susceptibility testing of Helicobacter pylori in liquid media. by Coudron PE, Stratton CW.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228094

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Familial clustering of Helicobacter pylori infection: population based study. by Dominici P, Bellentani S, Di Biase AR, Saccoccio G, Le Rose A, Masutti F, Viola L, Balli F, Tiribelli C, Grilli R, Fusillo M, Grossi E.; 1999 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28203

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Fluorescence Resonance Energy Transfer Microscopy of the Helicobacter pylori Vacuolating Cytotoxin within Mammalian Cells. by Willhite DC, Ye D, Blanke SR.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128058

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Frequency of vacA Genotypes and Cytotoxin Activity in Helicobacter pylori Associated with Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma. by Miehlke S, Meining A, Morgner A, Bayerdorffer E, Lehn N, Stolte M, Graham DY, Go MF.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105053

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Frequent Association between Alteration of the rdxA Gene and Metronidazole Resistance in French and North African Isolates of Helicobacter pylori. by Tankovic J, Lamarque D, Delchier JC, Soussy CJ, Labigne A, Jenks PJ.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89734

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Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori. by Xu Q, Morgan RD, Roberts RJ, Xu SY, van Doorn LJ, Donahue JP, Miller GG, Blaser MJ.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137426

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Functional analysis of putative restriction --modification system genes in the Helicobacter pylori J99 genome. by Kong H, Lin LF, Porter N, Stickel S, Byrd D, Posfai J, Roberts RJ.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110709

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Functional Analysis of the Helicobacter pylori cag Pathogenicity Island Reveals Both VirD4-CagA-Dependent and VirD4-CagA-Independent Mechanisms. by Selbach M, Moese S, Meyer TF, Backert S.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127714

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Functional Expression in Escherichia coli and Membrane Topology of Porin HopE, a Member of a Large Family of Conserved Proteins in Helicobacter pylori. by Bina J, Bains M, Hancock RE.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111296

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Furazolidone- and Nitrofurantoin-Resistant Helicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance. by Kwon DH, Lee M, Kim JJ, Kim JG, El-Zaatari FA, Osato MS, Graham DY.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90279

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Gastric Penetration of Amoxicillin in a Human Helicobacter pylori-Infected Xenograft Model. by Lozniewski A, Duprez A, Renault C, Muhale F, Conroy MC, Weber M, Le Faou A, Jehl F.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89389

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Gene Expression Profiling in AGS Cells Stimulated with Helicobacter pylori Isogenic Strains (cagA Positive or cagA Negative). by Bach S, Makristathis A, Rotter M, Hirschl AM.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127671

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Gene Expression Profiling of Helicobacter pylori Reveals a Growth-Phase-Dependent Switch in Virulence Gene Expression. by Thompson LJ, Merrell DS, Neilan BA, Mitchell H, Lee A, Falkow S.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153220

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Generation and Characterization of Human Monoclonal scFv Antibodies against Helicobacter pylori Antigens. by Reiche N, Jung A, Brabletz T, Vater T, Kirchner T, Faller G.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128126

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Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates. by Panthel K, Jechlinger W, Matis A, Rohde M, Szostak M, Lubitz W, Haas R.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143412

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Genome-Scale Metabolic Model of Helicobacter pylori 26695. by Schilling CH, Covert MW, Famili I, Church GM, Edwards JS, Palsson BO.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135230

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Genome-Wide Transcriptional Profiling in a Histidine Kinase Mutant of Helicobacter pylori Identifies Members of a Regulon. by Forsyth MH, Cao P, Garcia PP, Hall JD, Cover TL.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135264

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Genotypic Characterization of Clarithromycin-Resistant and -Susceptible Helicobacter pylori Strains from the Same Patient Demonstrates Existence of Two Unrelated Isolates. by Wang G, Jiang Q, Taylor DE.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105193

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Genotypic, Clinical, and Demographic Characteristics of Children Infected with Helicobacter pylori. by Gold BD, van Doorn LJ, Guarner J, Owens M, Pierce-Smith D, Song Q, Hutwagner L, Sherman PM, de Mola OL, Czinn SJ.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87938

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Growth and Survival of Helicobacter pylori in Defined Medium and Susceptibility to Brij 78. by Albertson N, Wenngren I, Sjostrom JE.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104805

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Growth of Helicobacter pylori in a long spiral form does not alter expression of immunodominant proteins. by Vinette KM, Gibney KM, Proujansky R, Fawcett PT.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126220

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Growth of Helicobacter pylori in media containing cyclodextrins. by Olivieri R, Bugnoli M, Armellini D, Bianciardi S, Rappuoli R, Bayeli PF, Abate L, Esposito E, de Gregorio L, Aziz J, et al.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262644

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Growth Phase-Dependent Regulation of Target Gene Promoters for Binding of the Essential Orphan Response Regulator HP1043 of Helicobacter pylori. by Delany I, Spohn G, Rappuoli R, Scarlato V.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135297

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Growth Supplements for Helicobacter pylori. by Jiang X, Doyle MP.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86644

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Helicobacter pylori ABC transporter: effect of allelic exchange mutagenesis on urease activity. by Hendricks JK, Mobley HL.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179482

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Helicobacter pylori Activates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells. by Hirata Y, Maeda S, Mitsuno Y, Akanuma M, Yamaji Y, Ogura K, Yoshida H, Shiratori Y, Omata M.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98458

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Helicobacter pylori Alters Exogenous Antigen Absorption and Processing in a Digestive Tract Epithelial Cell Line Model. by Matysiak-Budnik T, Terpend K, Alain S, Sanson le Pors MJ, Desjeux JF, Megraud F, Heyman M.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108731

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Helicobacter pylori and Neutrophils: Sialic Acid-Dependent Binding to Various Isolated Glycoconjugates. by Miller-Podraza H, Bergstrom J, Teneberg S, Milh MA, Longard M, Olsson BM, Uggla L, Karlsson KA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97034

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Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survival. by Gobert AP, McGee DJ, Akhtar M, Mendz GL, Newton JC, Cheng Y, Mobley HL, Wilson KT.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61129

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Helicobacter pylori Attachment to Gastric Cells Induces Cytoskeletal Rearrangements and Tyrosine Phosphorylation of Host Cell Proteins. by Segal ED, Falkow S, Tompkins LS.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40067

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Helicobacter pylori cagA Status and s and m Alleles of vacA in Isolates from Individuals with a Variety of H. pylori-Associated Gastric Diseases. by Evans DG, Queiroz DM, Mendes EN, Evans DJ Jr.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105353

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Helicobacter pylori Can Be Induced To Assume the Morphology of Helicobacter heilmannii. by Fawcett PT, Gibney KM, Vinette KM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88647

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Helicobacter pylori Containing Only Cytoplasmic Urease Is Susceptible to Acid. by Krishnamurthy P, Parlow M, Zitzer JB, Vakil NB, Mobley HL, Levy M, Phadnis SH, Dunn BE.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108630

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Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies. by Manetti R, Massari P, Burroni D, de Bernard M, Marchini A, Olivieri R, Papini E, Montecucco C, Rappuoli R, Telford JL.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173637

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Helicobacter pylori Does Not Require Lewis X or Lewis Y Expression To Colonize C3H/HeJ mice. by Takata T, El-Omar E, Camorlinga M, Thompson SA, Minohara Y, Ernst PB, Blaser MJ.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127983

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Helicobacter pylori expresses a complex surface carbohydrate, Lewis X. by Sherburne R, Taylor DE.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173655

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Helicobacter pylori Expresses an Autolytic Enzyme: Gene Identification, Cloning, and Theoretical Protein Structure. by Marsich E, Zuccato P, Rizzi S, Vetere A, Tonin E, Paoletti S.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151945

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Helicobacter pylori genetic diversity within the gastric niche of a single human host. by Israel DA, Salama N, Krishna U, Rieger UM, Atherton JC, Falkow S, Peek RM Jr.; 2001 Dec 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64732

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Helicobacter pylori Glutamine Synthetase Lacks Features Associated with Transcriptional and Posttranslational Regulation. by Garner RM, Fulkerson J Jr, Mobley HL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108133

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Helicobacter pylori Growth and Urease Detection in the Chemically Defined Medium Ham's F-12 Nutrient Mixture. by Testerman TL, McGee DJ, Mobley HL.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88453

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Helicobacter pylori Heat Shock Protein A: Serologic Responses and Genetic Diversity. by Ng EK, Thompson SA, Perez-Perez GI, Kansau I, van der Ende A, Labigne A, Sung JJ, Chung SC, Blaser MJ.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103726

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Helicobacter pylori Infection in an Urban African Population. by Fernando N, Holton J, Zulu I, Vaira D, Mwaba P, Kelly P.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87933

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Helicobacter pylori Infection Induces Interleukin-8 Receptor Expression in the Human Gastric Epithelium. by Backhed F, Torstensson E, Seguin D, Richter-Dahlfors A, Rokbi B.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155779

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Helicobacter pylori Interactions with Host Serum and Extracellular Matrix Proteins: Potential Role in the Infectious Process. by Dubreuil JD, Giudice GD, Rappuoli R.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134656

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Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains. by Aras RA, Small AJ, Ando T, Blaser MJ.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140068

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Helicobacter pylori Intrafamilial Infections: Change in Source of Infection of a Child from Father to Mother after Eradication Therapy. by Taneike I, Tamura Y, Shimizu T, Yamashiro Y, Yamamoto T.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96135

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Helicobacter pylori isolated from the domestic cat: public health implications. by Handt LK, Fox JG, Dewhirst FE, Fraser GJ, Paster BJ, Yan LL, Rozmiarek H, Rufo R, Stalis IH.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186520

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Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14. by Kirkland T, Viriyakosol S, Perez-Perez GI, Blaser MJ.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176102

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Helicobacter pylori Mutants Defective in RuvC Holliday Junction Resolvase Display Reduced Macrophage Survival and Spontaneous Clearance from the Murine Gastric Mucosa. by Loughlin MF, Barnard FM, Jenkins D, Sharples GJ, Jenks PJ.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152077

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Helicobacter pylori Physiology Predicted from Genomic Comparison of Two Strains. by Doig P, de Jonge BL, Alm RA, Brown ED, Uria-Nickelsen M, Noonan B, Mills SD, Tummino P, Carmel G, Guild BC, Moir DT, Vovis GF, Trust TJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103750

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Helicobacter pylori porCDAB and oorDABC Genes Encode Distinct Pyruvate:Flavodoxin and 2-Oxoglutarate:Acceptor Oxidoreductases Which Mediate Electron Transport to NADP. by Hughes NJ, Clayton CL, Chalk PA, Kelly DJ.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106998

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Helicobacter pylori Pore-Forming Cytolysin Orthologue TlyA Possesses In Vitro Hemolytic Activity and Has a Role in Colonization of the Gastric Mucosa. by Martino MC, Stabler RA, Zhang ZW, Farthing MJ, Wren BW, Dorrell N.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98074

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Helicobacter pylori Possesses Two CheY Response Regulators and a Histidine Kinase Sensor, CheA, Which Are Essential for Chemotaxis and Colonization of the Gastric Mucosa. by Foynes S, Dorrell N, Ward SJ, Stabler RA, McColm AA, Rycroft AN, Wren BW.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97381

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Helicobacter pylori Primary Resistance to Metronidazole and Clarithromycin in Brazil. by Prazeres Magalhaes P, de Magalhaes Queiroz DM, Campos Barbosa DV, Aguiar Rocha G, Nogueira Mendes E, Santos A, Valle Correa PR, Camargos Rocha AM, Martins Teixeira L, Affonso de Oliveira C.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127243

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Helicobacter pylori requires an acidic environment to survive in the presence of urea. by Clyne M, Labigne A, Drumm B.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173208

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Helicobacter pylori Resists Phagocytosis by Macrophages: Quantitative Assessment by Confocal Microscopy and Fluorescence-Activated Cell Sorting. by Ramarao N, Meyer TF.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98197

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Helicobacter pylori ribBA-Mediated Riboflavin Production Is Involved in Iron Acquisition. by Worst DJ, M. Gerrits M, Vandenbroucke-Grauls CM, Kusters JG.; 1998 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107047

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Helicobacter pylori rocF Is Required for Arginase Activity and Acid Protection In Vitro but Is Not Essential for Colonization of Mice or for Urease Activity. by McGee DJ, Radcliff FJ, Mendz GL, Ferrero RL, Mobley HL.; 1999 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103695

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Helicobacter pylori Uptake and Efflux: Basis for Intrinsic Susceptibility to Antibiotics In Vitro. by Bina JE, Alm RA, Uria-Nickelsen M, Thomas SR, Trust TJ, Hancock RE.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89666

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Helicobacter pylori Urease Suppresses Bactericidal Activity of Peroxynitrite via Carbon Dioxide Production. by Kuwahara H, Miyamoto Y, Akaike T, Kubota T, Sawa T, Okamoto S, Maeda H.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98327

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Helicobacter pylori. by Dunn BE, Cohen H, Blaser MJ.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172942

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Helicobacter pylori: a Eubacterium Lacking the Stringent Response. by Scoarughi GL, Cimmino C, Donini P.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93409

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Helicobacter pylori: Clonal Population Structure and Restricted Transmission within Families Revealed by Molecular Typing. by Han SR, Zschausch HC, Meyer HG, Schneider T, Loos M, Bhakdi S, Maeurer MJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87450

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Helicobacter pylori-Associated Gastritis in Mice is Host and Strain Specific. by van Doorn NE, Namavar F, Sparrius M, Stoof J, van Rees EP, van Doorn LJ, VandenbrouckeGrauls CM.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96618

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Helicobacter pylori-induced gastritis in the domestic cat. by Fox JG, Batchelder M, Marini R, Yan L, Handt L, Li X, Shames B, Hayward A, Campbell J, Murphy JC.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173358

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Heterogeneity in Levels of Vacuolating Cytotoxin Gene (vacA) Transcription among Helicobacter pylori Strains. by Forsyth MH, Atherton JC, Blaser MJ, Cover TL.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108317

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Heterogeneity in susceptibility to metronidazole among Helicobacter pylori isolates from patients with gastritis or peptic ulcer disease. by Weel JF, van der Hulst RW, Gerrits Y, Tytgat GN, van der Ende A, Dankert J.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229209

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Heterogeneity of Immunoglobulin G Response to Helicobacter pylori Measured by the Unweighted Pair Group Method with Averages. by Mayo K, Pretolani S, Gasbarrini G, Ghironzi G, Megraud F.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121394

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High Prevalence of cagA- and babA2-Positive Helicobacter pylori Clinical Isolates in Taiwan. by Lai CH, Kuo CH, Chen YC, Chao FY, Poon SK, Chang CS, Wang WC.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130881

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High-Level [beta]-Lactam Resistance Associated with Acquired Multidrug Resistance in Helicobacter pylori. by Kwon DH, Dore MP, Kim JJ, Kato M, Lee M, Wu JY, Graham DY.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161855

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Houseflies Are an Unlikely Reservoir or Vector for Helicobacter pylori. by Osato MS, Ayub K, Le HH, Reddy R, Graham DY.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105211

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HP0333, a Member of the dprA Family, Is Involved in Natural Transformation in Helicobacter pylori. by Ando T, Israel DA, Kusugami K, Blaser MJ.; 1999 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94075

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Human Embryonic Gastric Xenografts in Nude Mice: a New Model of Helicobacter pylori Infection. by Lozniewski A, Muhale F, Hatier R, Marais A, Conroy MC, Edert D, le Faou A, Weber M, Duprez A.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96530

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iceA Genotypes of Helicobacter pylori Strains Isolated from Brazilian Children and Adults. by Ashour AA, Birchal Collares G, Nogueira Mendes E, Ribeiro de Gusmao V, Queiroz DM, Prazeres Magalhaes P, Teles de Carvalho AS, de Oliveira CA, Ferreira Nogueira AM, Aguiar Rocha G, Rocha AM.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88019

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Identification and Analysis of a New vacA Genotype Variant of Helicobacter pylori in Different Patient Groups in Germany. by Strobel S, Bereswill S, Balig P, Allgaier P, Sonntag HG, Kist M.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104815

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Identification and characterization of an operon of Helicobacter pylori that is involved in motility and stress adaptation. by Beier D, Spohn G, Rappuoli R, Scarlato V.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179311

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Identification by RNA Profiling and Mutational Analysis of the Novel Copper Resistance Determinants CrdA (HP1326), CrdB (HP1327), and CzcB (HP1328) in Helicobacter pylori. by Waidner B, Melchers K, Ivanov I, Loferer H, Bensch KW, Kist M, Bereswill S.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135432

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Identification of a Novel Penicillin-Binding Protein from Helicobacter pylori. by Krishnamurthy P, Parlow MH, Schneider J, Burroughs S, Wickland C, Vakil NB, Dunn BE, Phadnis SH.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94005

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Identification of a putative chromosomal replication origin from Helicobacter pylori and its interaction with the initiator protein DnaA. by Zawilak A, Cebrat S, Mackiewicz P, Krol-Hulewicz A, Jakimowicz D, Messer W, Gosciniak G, ZakrzewskaCzerwinska J.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55718

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Identification of an Antigenic Epitope in Helicobacter pylori Urease That Induces Neutralizing Antibody Production. by Hirota K, Nagata K, Norose Y, Futagami S, Nakagawa Y, Senpuku H, Kobayashi M, Takahashi H.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100032

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Identification of cagA Tyrosine Phosphorylation DNA Motifs in Helicobacter pylori Isolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays. by Owen RJ, Sharp SI, Chisholm SA, Rijpkema S.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165352

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Identification of Helicobacter pylori and Other Helicobacter Species by PCR, Hybridization, and Partial DNA Sequencing in Human Liver Samples from Patients with Primary Sclerosing Cholangitis or Primary Biliary Cirrhosis. by Nilsson HO, Taneera J, Castedal M, Glatz E, Olsson R, Wadstrom T.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86342

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Identification of Helicobacter pylori by immunological dot blot method based on reaction of a species-specific monoclonal antibody with a surface-exposed protein. by Bolin I, Lonroth H, Svennerholm AM.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227952

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Identification of Potential Diagnostic and Vaccine Candidates of Helicobacter pylori by Two-Dimensional Gel Electrophoresis, Sequence Analysis, and Serum Profiling. by McAtee CP, Lim MY, Fung K, Velligan M, Fry K, Chow T, Berg DE.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95614

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Identification of Target Genes Regulated by the Two-Component System HP166HP165 of Helicobacter pylori. by Dietz P, Gerlach G, Beier D.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139590

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Identification of type II restriction and modification systems in Helicobacter pylori reveals their substantial diversity among strains. by Xu Q, Morgan RD, Roberts RJ, Blaser MJ.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16923

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Identification of Virulence Genes of Helicobacter pylori by Random Insertion Mutagenesis. by Bijlsma JJ, Vandenbroucke-Grauls CM, Phadnis SH, Kusters JG.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115989

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Identification, characterization, and immunogenicity of the lactoferrin-binding protein from Helicobacter pylori. by Dhaenens L, Szczebara F, Husson MO.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176089

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Identification, characterization, and spatial localization of two flagellin species in Helicobacter pylori flagella. by Kostrzynska M, Betts JD, Austin JW, Trust TJ.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207209

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Immune Response against a Cross-Reactive Epitope on the Heat Shock Protein 60 Homologue of Helicobacter pylori. by Yamaguchi H, Osaki T, Kai M, Taguchi H, Kamiya S.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97622

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Immune Response to an 18-Kilodalton Outer Membrane Antigen Identifies Lipoprotein 20 as a Helicobacter pylori Vaccine Candidate. by Keenan J, Oliaro J, Domigan N, Potter H, Aitken G, Allardyce R, Roake J.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97594

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Immunization with Recombinant Helicobacter pylori Urease in Specific-PathogenFree Rhesus Monkeys (Macaca mulatta). by Solnick JV, Canfield DR, Hansen LM, Torabian SZ.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97459

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Immunoblot Analysis of Humoral Immune Response to Helicobacter pylori in Children with and without Duodenal Ulcer. by Rocha GA, Oliveira AM, Queiroz DM, Carvalho AS, Nogueira AM.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86586

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Immunoglobulin G Antibody Response to Infection with Coccoid Forms of Helicobacter pylori. by Figueroa G, Faundez G, Troncoso M, Navarrete P, Toledo MS.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120064

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Immunomagnetic separation and PCR for detection of Helicobacter pylori in water and stool specimens. by Enroth H, Engstrand L.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228356

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Implication of the Structure of the Helicobacter pylori cag Pathogenicity Island in Induction of Interleukin-8 Secretion. by Audibert C, Burucoa C, Janvier B, Fauchere JL.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98065

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Importance in diagnosis of gastritis of detection by PCR of the cagA gene in Helicobacter pylori strains isolated from children. by Husson MO, Gottrand F, Vachee A, Dhaenens L, de la Salle EM, Turck D, Houcke M, Leclerc H.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228692

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In Vitro and In Vivo Activities of Tea Catechins against Helicobacter pylori. by Mabe K, Yamada M, Oguni I, Takahashi T.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89367

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In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pylori Infection. by Kanamaru T, Nakano Y, Toyoda Y, Miyagawa KI, Tada M, Kaisho T, Nakao M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90677

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In Vivo Behavior of a Helicobacter pylori SS1 nixA Mutant with Reduced Urease Activity. by Nolan KJ, McGee DJ, Mitchell HM, Kolesnikow T, Harro JM, O'Rourke J, Wilson JE, Danon SJ, Moss ND, Mobley HL, Lee A.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127660

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In Vivo Complementation of ureB Restores the Ability of Helicobacter pylori To Colonize. by Eaton KA, Gilbert JV, Joyce EA, Wanken AE, Thevenot T, Baker P, Plaut A, Wright A.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127652

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Inactivation of Helicobacter pylori by chlorination. by Johnson CH, Rice EW, Reasoner DJ.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168826

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Increasing Multidrug Resistance in Helicobacter pylori Strains Isolated from Children and Adults in Mexico. by Torres J, Camorlinga-Ponce M, Perez-Perez G, Madrazo-De la Garza A, Dehesa M, Gonzalez-Valencia G, Munoz O.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88210

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Induction of Monocyte Chemoattractant Protein 1 by Helicobacter pylori Involves NF-[kappa]B. by Mori N, Ueda A, Geleziunas R, Wada A, Hirayama T, Yoshimura T, Yamamoto N.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98018

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Influence of Culture Conditions on the Fatty Acid Profiles of Laboratory-Adapted and Freshly Isolated Strains of Helicobacter pylori. by Scherer C, Muller KD, Rath PM, Ansorg RA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150301

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Influence of Lewis Antigen Expression by Helicobacter pylori on Bacterial Internalization by Gastric Epithelial Cells. by Lozniewski A, Haristoy X, Rasko DA, Hatier R, Plenat F, Taylor DE, Angioi-Duprez K.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153228

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Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. by Simon PM, Goode PL, Mobasseri A, Zopf D.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176121

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Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease. by Nagata K, Takagi E, Tsuda M, Nakazawa T, Satoh H, Nakao M, Okamura H, Tamura T.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162584

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Inhibitory Activities of Lansoprazole against Respiration in Helicobacter pylori. by Nagata K, Sone N, Tamura T.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90499

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Insertion of Mini-IS605 and Deletion of Adjacent Sequences in the Nitroreductase (rdxA) Gene Cause Metronidazole Resistance in Helicobacter pylori NCTC11637. by Debets-Ossenkopp YJ, Pot RG, van Westerloo DJ, Goodwin A, Vandenbroucke-Grauls CM, Berg DE, Hoffman PS, Kusters JG.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89539

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Intercellular Communication in Helicobacter pylori: luxS Is Essential for the Production of an Extracellular Signaling Molecule. by Forsyth MH, Cover TL.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97560

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Interference of Pseudomonas Strains in the Identification of Helicobacter pylori. by Dominguez-Bello MG, Reyes N, Teppa-Garran A, Romero R.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86256

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Iron-Dependent Transcription of the frpB Gene of Helicobacter pylori Is Controlled by the Fur Repressor Protein. by Delany I, Pacheco AB, Spohn G, Rappuoli R, Scarlato V.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99551

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Iron-repressible outer membrane proteins of Helicobacter pylori involved in heme uptake. by Worst DJ, Otto BR, de Graaff J.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173585

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Isolation and biochemical and molecular analyses of a species-specific protein antigen from the gastric pathogen Helicobacter pylori. by O'Toole PW, Logan SM, Kostrzynska M, Wadstrom T, Trust TJ.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207039

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Isolation and characterization of a conserved porin protein from Helicobacter pylori. by Doig P, Exner MM, Hancock RE, Trust TJ.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177350

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Isolation and characterization of a family of porin proteins from Helicobacter pylori. by Exner MM, Doig P, Trust TJ, Hancock RE.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173190

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Isolation and Characterization of Tetracycline-Resistant Clinical Isolates of Helicobacter pylori. by Kwon DH, Kim JJ, Lee M, Yamaoka Y, Kato M, Osato MS, ElZaatari FA, Graham DY.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101634

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Isolation and Genotyping of Helicobacter pylori from Untreated Municipal Wastewater. by Lu Y, Redlinger TE, Avitia R, Galindo A, Goodman K.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123781

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Isolation of Helicobacter pylori Genes That Modulate Urease Activity. by McGee DJ, May CA, Garner RM, Himpsl JM, Mobley HL.; 1999 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93674

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Isolation of Recombinant Protective Helicobacter pylori Antigens. by Hocking D, Webb E, Radcliff F, Rothel L, Taylor S, Pinczower G, Kapouleas C, Braley H, Lee A, Doidge C.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96799

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Isolation of the Helicobacter pylori recA gene and involvement of the recA region in resistance to low pH. by Thompson SA, Blaser MJ.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173284

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Local Secretory Immunoglobulin A and Postimmunization Gastritis Correlate with Protection against Helicobacter pylori Infection after Oral Vaccination of Mice. by Goto T, Nishizono A, Fujioka T, Ikewaki J, Mifune K, Nasu M.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116000

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Long-term colonization with single and multiple strains of Helicobacter pylori assessed by DNA fingerprinting. by Taylor NS, Fox JG, Akopyants NS, Berg DE, Thompson N, Shames B, Yan L, Fontham E, Janney F, Hunter FM.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228068

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Macrolide resistance in Helicobacter pylori: mechanism and stability in strains from clarithromycin-treated patients. by Hulten K, Gibreel A, Skold O, Engstrand L.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164161

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Macrolide resistance in Helicobacter pylori: rapid detection of point mutations and assays of macrolide binding to ribosomes. by Occhialini A, Urdaci M, DoucetPopulaire F, Bebear CM, Lamouliatte H, Megraud F.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164196

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Magnesium Uptake by CorA Is Essential for Viability of the Gastric Pathogen Helicobacter pylori. by Pfeiffer J, Guhl J, Waidner B, Kist M, Bereswill S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128062

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Magnetic Immuno-PCR Assay with Inhibitor Removal for Direct Detection of Helicobacter pylori in Human Feces. by Monteiro L, Gras N, Megraud F.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88433

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Mechanism of Metronidazole Resistance in Helicobacter pylori: Comparison of the rdxA Gene Sequences in 30 Strains. by Solca NM, Bernasconi MV, Piffaretti JC.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90043

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Membrane Topology of the NixA Nickel Transporter of Helicobacter pylori: Two Nickel Transport-Specific Motifs within Transmembrane Helices II and III. by Fulkerson JF Jr, Mobley HL.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94471

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Metabolic activities of metronidazole-sensitive and -resistant strains of Helicobacter pylori: repression of pyruvate oxidoreductase and expression of isocitrate lyase activity correlate with resistance. by Hoffman PS, Goodwin A, Johnsen J, Magee K, Veldhuyzen van Zanten SJ.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178263

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Metabolism and Genetics of Helicobacter pylori: the Genome Era. by Marais A, Mendz GL, Hazell SL, Megraud F.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103749

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Metronidazole Activation Is Mutagenic and Causes DNA Fragmentation in Helicobacter pylori and in Escherichia coli Containing a Cloned H. pylori rdxA + (Nitroreductase) Gene. by Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, LimMorrison S, Raudonikiene A, Berg DE, Hoffman PS.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94656

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Metronidazole and clarithromycin resistance in Helicobacter pylori determined by measuring MICs of antimicrobial agents in color indicator egg yolk agar in a miniwell format. The Gastrointestinal Physiology Working Group of Universidad Peruana Cayetano Heredia and the Johns Hopkins University. by Vasquez A, Valdez Y, Gilman RH, McDonald JJ, Westblom TU, Berg D, Mayta H, Gutierrez V.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228988

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Microtiter Assay for Detecting Campylobacter spp. and Helicobacter pylori with Surface Gangliosides Which Bind Cholera Toxin. by Sack DA, Lastovica AJ, Chang SH, Pazzaglia G.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104975

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Modification in the ppk Gene of Helicobacter pylori during Single and Multiple Experimental Murine Infections. by Ayraud S, Janvier B, Salaun L, Fauchere JL.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152028

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Molecular Characterization of a Flagellar Export Locus of Helicobacter pylori. by Porwollik S, Noonan B, O'Toole PW.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115938

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Molecular Characterization of the 128-kDa Immunodominant Antigen of Helicobacter pylori Associated with Cytotoxicity and Duodenal Ulcer. by Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N, Rappuoli R.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46808

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Molecular Cloning and Characterization of the Helicobacter pylori fliD Gene, an Essential Factor in Flagellar Structure and Motility. by Seong Kim J, Hoon Chang J, Il Chung S, Sun Yum J.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94171

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Molecular Patchwork: Chromosomal Recombination between Two Helicobacter pylori Strains during Natural Colonization. by Smeets LC, Arents NL, van Zwet AA, Vandenbroucke-Grauls CM, Verboom T, Bitter W, Kusters JG.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153253

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Molecular typing of Helicobacter pylori isolates from a multicenter U.S. clinical trial by ureC restriction fragment length polymorphism. by Shortridge VD, Stone GG, Flamm RK, Beyer J, Versalovic J, Graham DW, Tanaka SK.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229602

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Motility of Helicobacter pylori Is Coordinately Regulated by the Transcriptional Activator FlgR, an NtrC Homolog. by Spohn G, Scarlato V.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93415

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Mouse-Colonizing Helicobacter pylori SS1 Is Unusually Susceptible to Metronidazole Due to Two Complementary Reductase Activities. by Jeong JY, Berg DE.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101615

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Mucoadhesive Microspheres Containing Amoxicillin for Clearance of Helicobacter pylori. by Nagahara N, Akiyama Y, Nakao M, Tada M, Kitano M, Ogawa Y.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105867

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Multiple Genes in the Left Half of the cag Pathogenicity Island of Helicobacter pylori Are Required for Tyrosine Kinase-Dependent Transcription of Interleukin-8 in Gastric Epithelial Cells. by Li SD, Kersulyte D, Lindley IJ, Neelam B, Berg DE, Crabtree JE.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96669

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Multiplex Sequence Analysis Demonstrates the Competitive Growth Advantage of the A-to-G Mutants of Clarithromycin-Resistant Helicobacter pylori. by Wang G, Rahman MS, Humayun MZ, Taylor DE.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89182

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Murine Splenocytes Induce Severe Gastritis and Delayed-Type Hypersensitivity and Suppress Bacterial Colonization in Helicobacter pylori-Infected SCID Mice. by Eaton KA, Ringler SR, Danon SJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96783

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Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. by Bjorkholm B, Sjolund M, Falk PG, Berg OG, Engstrand L, Andersson DI.; 2001 Dec 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64729

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Mutational Analysis of Genes Encoding the Early Flagellar Components of Helicobacter pylori: Evidence for Transcriptional Regulation of Flagellin A Biosynthesis. by Allan E, Dorrell N, Foynes S, Anyim M, Wren BW.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94681

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Mutational Analysis of the Helicobacter pylori Vacuolating Toxin Amino Terminus: Identification of Amino Acids Essential for Cellular Vacuolation. by Ye D, Blanke SR.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101768

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Mutations at Four Distinct Regions of the rpoB Gene Can Reduce the Susceptibility of Helicobacter pylori to Rifamycins. by Heep M, Odenbreit S, Beck D, Decker J, Prohaska E, Rieger U, Lehn N.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89941

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Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. by Versalovic J, Shortridge D, Kibler K, Griffy MV, Beyer J, Flamm RK, Tanaka SK, Graham DY, Go MF.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163139

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Mutations in 23S rRNA in Helicobacter pylori Conferring Resistance to Erythromycin Do Not Always Confer Resistance to Clarithromycin. by Garcia-Arata MI, Baquero F, de Rafael L, de Argila CM, Gisbert JP, Bermejo F, Boixeda D, Canton R.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89082

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Mutations in the 16S rRNA Genes of Helicobacter pylori Mediate Resistance to Tetracycline. by Trieber CA, Taylor DE.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134973

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Mutations in the Beginning of the rpoB Gene Can Induce Resistance to Rifamycins in both Helicobacter pylori and Mycobacterium tuberculosis. by Heep M, Rieger U, Beck D, Lehn N.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89817

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Mutations of the Helicobacter pylori Genes rdxA and pbp1 Cause Resistance against Metronidazole and Amoxicillin. by Paul R, Postius S, Melchers K, Schafer KP.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90405

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Natural Diversity in the N Terminus of the Mature Vacuolating Cytotoxin of Helicobacter pylori Determines Cytotoxin Activity. by Letley DP, Atherton JC.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94518

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Neutrophil-Activating Protein Mediates Adhesion of Helicobacter pylori to Sulfated Carbohydrates on High-Molecular-Weight Salivary Mucin. by Namavar F, Sparrius M, Veerman EC, Appelmelk BJ, Vandenbroucke-Grauls CM.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107925

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New Pathogenicity Marker Found in the Plasticity Region of the Helicobacter pylori Genome. by Santos A, Queiroz DM, Menard A, Marais A, Rocha GA, Oliveira CA, Nogueira AM, Uzeda M, Megraud F.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153914

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New plate medium for growth and detection of urease activity of Helicobacter pylori. by Cellini L, Allocati N, Piccolomini R, Di Campli E, Dainelli B.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265285

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New Site of Modification of 23S rRNA Associated with Clarithromycin Resistance of Helicobacter pylori Clinical Isolates. by Fontana C, Favaro M, Minelli S, Criscuolo AA, Pietroiusti A, Galante A, Favalli C.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132752

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Nickel-Responsive Induction of Urease Expression in Helicobacter pylori Is Mediated at the Transcriptional Level. by van Vliet AH, Kuipers EJ, Waidner B, Davies BJ, de Vries N, Penn CW, Vandenbroucke-Grauls CM, Kist M, Bereswill S, Kusters JG.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98579

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NikR Mediates Nickel-Responsive Transcriptional Induction of Urease Expression in Helicobacter pylori. by van Vliet AH, Poppelaars SW, Davies BJ, Stoof J, Bereswill S, Kist M, Penn CW, Kuipers EJ, Kusters JG.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128006

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Novel Method for Rapid Determination of Clarithromycin Sensitivity in Helicobacter pylori. by Gibson JR, Saunders NA, Burke B, Owen RJ.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85748

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Nucleotide Sequence and Characterization of cdrA, a Cell Division-Related Gene of Helicobacter pylori. by Takeuchi H, Shirai M, Akada JK, Tsuda M, Nakazawa T.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107570

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Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori. by Moore RA, Beckthold B, Wong S, Kureishi A, Bryan LE.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162494

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Nutritional requirements for growth of Helicobacter pylori. by Nedenskov P.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201830

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Optimal combination of media for primary isolation of Helicobacter pylori from gastric biopsy specimens. by Piccolomini R, Di Bonaventura G, Festi D, Catamo G, Laterza F, Neri M.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229783

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Oxidative-Stress Resistance Mutants of Helicobacter pylori. by Olczak AA, Olson JW, Maier RJ.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135082

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Partial characterization and effect of omeprazole on ATPase activity in Helicobacter pylori by using permeabilized cells. by Belli WA, Fryklund J.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162814

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Partial characterization of a cell proliferation-inhibiting protein produced by Helicobacter pylori. by Knipp U, Birkholz S, Kaup W, Opferkuch W.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174253

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Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization. by O'Rourke EJ, Chevalier C, Pinto AV, Thiberge JM, Ielpi L, Labigne A, Radicella JP.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151419

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Pathogenicity of Helicobacter pylori: a perspective. by Lee A, Fox J, Hazell S.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280741

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PCR detection of colonization by Helicobacter pylori in conventional, euthymic mice based on the 16S ribosomal gene sequence. by Smith JG, Kong L, Abruzzo GK, Gill CJ, Flattery AM, Scott PM, Bramhill D, Cioffe C, Thompson CM, Bartizal K.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170249

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PCR Using 3[prime prime or minute]-Mismatched Primers To Detect A2142C Mutation in 23S rRNA Conferring Resistance to Clarithromycin in Helicobacter pylori Clinical Isolates. by Alarcon T, Domingo D, Prieto N, Lopez-Brea M.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86249

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PCR-Based Diagnosis of Helicobacter pylori Infection and Real-Time Determination of Clarithromycin Resistance Directly from Human Gastric Biopsy Samples. by Chisholm SA, Owen RJ, Teare EL, Saverymuttu S.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87913

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PCR-based restriction fragment length polymorphism typing of Helicobacter pylori. by Fujimoto S, Marshall B, Blaser MJ.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263033

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PCR-Based Restriction Pattern Typing of the vacA Gene Provides Evidence for a Homogeneous Group among Helicobacter pylori Strains Associated with Peptic Ulcer Disease. by Donati M, Storni E, D'Apote L, Moreno S, Tucci A, Poli L, Cevenini R.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88623

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PCR-based RFLP analysis of DNA sequence diversity in the gastric pathogen Helicobacter pylori. by Akopyanz N, Bukanov NO, Westblom TU, Berg DE.; 1992 Dec 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334508

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PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori. by Akopyants NS, Fradkov A, Diatchenko L, Hill JE, Siebert PD, Lukyanov SA, Sverdlov ED, Berg DE.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23726

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Performance Characteristics of an Enzyme-Linked Immunosorbent Assay for Determining Salivary Immunoglobulin G Response to Helicobacter pylori. by De Pascalis R, Del Pezzo M, Nardone G, Budillon G, Lavitola A.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84329

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Performance Criteria of DNA Fingerprinting Methods for Typing of Helicobacter pylori Isolates: Experimental Results and Meta-Analysis. by Burucoa C, Lhomme V, Fauchere JL.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85883

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Pharmacodynamic effects of antibiotics and acid pump inhibitors on Helicobacter pylori. by Sorberg M, Hanberger H, Nilsson M, Nilsson LE.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164096

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157

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Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide. by Appelmelk BJ, Martino MC, Veenhof E, Monteiro MA, Maaskant JJ, Negrini R, Lindh F, Perry M, Del Giudice G, Vandenbroucke-Grauls CM.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101556

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Phase Variation in Helicobacter pylori Lipopolysaccharide. by Appelmelk BJ, Shiberu B, Trinks C, Tapsi N, Zheng PY, Verboom T, Maaskant J, Hokke CH, Schiphorst WE, Blanchard D, Simoons-Smit IM, van den Eijnden DH, Vandenbroucke-Grauls CM.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107860

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Phase Variation in the Helicobacter pylori Phospholipase A Gene and Its Role in Acid Adaptation. by Tannaes T, Dekker N, Bukholm G, Bijlsma JJ, Appelmelk BJ.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98819

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Phenotypic and genotypic variation in methylases involved in type II restrictionmodification systems in Helicobacter pylori. by Takata T, Aras R, Tavakoli D, Ando T, Olivares AZ, Blaser MJ.; 2002 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117188

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Phenotypic Variation of Helicobacter pylori Isolates from Geographically Distinct Regions Detected by Lectin Typing. by Hynes SO, Broutet N, Wadstrom T, Mikelsaar M, O'Toole PW, Telford J, Engstrand L, Kamiya S, Mentis AF, Moran AP.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120102

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pH-Regulated Gene Expression of the Gastric Pathogen Helicobacter pylori. by Merrell DS, Goodrich ML, Otto G, Tompkins LS, Falkow S.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155744

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Polymorphisms of Helicobacter pylori HP0638 Reflect Geographic Origin and Correlate with cagA Status. by Ando T, Peek RM, Pride D, Levine SM, Takata T, Lee YC, Kusugami K, van der Ende A, Kuipers EJ, Kusters JG, Blaser MJ.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120108

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Positive Result by Serology Indicates Active Helicobacter pylori Infection in Patients with Atrophic Gastritis. by Kokkola A, Rautelin H, Puolakkainen P, Sipponen P, Farkkila M, Haapiainen R, Kosunen TU.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104930

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Posttreatment Follow-Up of Helicobacter pylori Infection Using a Stool Antigen Immunoassay. by Roth DE, Taylor DN, Gilman RH, Meza R, Katz U, Bautista C, Cabrera L, Velapatino B, Lebron C, Razuri M, Watanabe J, Monath T.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96133

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Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells. by Nagata K, Satoh H, Iwahi T, Shimoyama T, Tamura T.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187756

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Prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease: systematic review. by Raghunath A, Hungin AP, Wooff D, Childs S.; 2003 Apr 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152634

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Prevalence of Helicobacter pylori in Sri Lanka as Determined by PCR. by Fernando N, Holton J, Vaira D, DeSilva M, Fernando D.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120560

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Production of a conserved adhesin by the human gastroduodenal pathogen Helicobacter pylori. by Doig P, Austin JW, Kostrzynska M, Trust TJ.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205892

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Promoters of the CATG-Specific Methyltransferase Gene hpyIM Differ between iceA1 and iceA2 Helicobacter pylori Strains. by Xu Q, Blaser MJ.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95269

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Protein Hpn: cloning and characterization of a histidine-rich metal-binding polypeptide in Helicobacter pylori and Helicobacter mustelae. by Gilbert JV, Ramakrishna J, Sunderman FW Jr, Wright A, Plaut AG.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173359

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Proteins Encoded by the cag Pathogenicity Island of Helicobacter pylori Are Required for NF-[kappa]B Activation. by Glocker E, Lange C, Covacci A, Bereswill S, Kist M, Pahl HL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108202

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Proteins Released by Helicobacter pylori In Vitro. by Kim N, Weeks DL, Shin JM, Scott DR, Young MK, Sachs G.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151949

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Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. by Spiegelhalder C, Gerstenecker B, Kersten A, Schiltz E, Kist M.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281317

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Quantification of conserved antigens in Helicobacter pylori during different culture conditions. by Lindholm C, Osek J, Svennerholm AM.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175778

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Quantitative Detection of Helicobacter pylori Gene Expression In Vivo and Relationship to Gastric Pathology. by Peek RM Jr, van Doorn LJ, Donahue JP, Tham KT, Figueiredo C, Blaser MJ, Miller GG.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101496

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Quantitative Evaluation of Inflammatory and Immune Responses in the Early Stages of Chronic Helicobacter pylori Infection. by Straubinger RK, Greiter A, McDonough SP, Gerold A, Scanziani E, Soldati S, Dailidiene D, Dailide G, Berg DE, Simpson KW.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153233

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Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments. by Furuta T, Kaneko E, Suzuki M, Arai H, Futami H.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229284

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Rapid and Accurate Determination of Genotypic Clarithromycin Resistance in Cultured Helicobacter pylori by Fluorescent In Situ Hybridization. by Russmann H, Adler K, Haas R, Gebert B, Koletzko S, Heesemann J.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88500

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Rapid detection of Helicobacter pylori in gastric biopsy material by polymerase chain reaction. by Hammar M, Tyszkiewicz T, Wadstrom T, O'Toole PW.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264995

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Rapid Detection of Mutations in the 23S rRNA Gene of Helicobacter pylori That Confers Resistance to Clarithromycin Treatment to the Bacterium. by Matsumura M, Hikiba Y, Ogura K, Togo G, Tsukuda I, Ushikawa K, Shiratori Y, Omata M.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87798

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Rapid Detection, by PCR and Reverse Hybridization, of Mutations in the Helicobacter pylori 23S rRNA Gene, Associated with Macrolide Resistance. by van Doorn LJ, Debets-Ossenkopp YJ, Marais A, Sanna R, Megraud F, Kusters JG, Quint WG.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89365

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Rapid genetic analysis of Helicobacter pylori gastric mucosal colonization in suckling mice. by Guo BP, Mekalanos JJ.; 2002 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123071

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Rapid PCR Detection of Helicobacter pylori-Associated Virulence and Resistance Genes Directly from Gastric Biopsy Material. by Bjorkholm B, Befrits R, Jaup B, Engstrand L.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105265

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Rare Incidence of Interspousal Transmission of Helicobacter pylori in Asymptomatic Individuals in Japan. by Suzuki J, Muraoka H, Kobayasi I, Fujita T, Mine T.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85917

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Reactivities of Lewis antigen monoclonal antibodies with the lipopolysaccharides of Helicobacter pylori strains isolated from patients with gastroduodenal diseases in Japan. by Amano K, Hayashi S, Kubota T, Fujii N, Yokota S.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170591

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Real-Time PCR Assay for Rapid and Accurate Detection of Point Mutations Conferring Resistance to Clarithromycin in Helicobacter pylori. by Oleastro M, Menard A, Santos A, Lamouliatte H, Monteiro L, Barthelemy P, Megraud F.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149634

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Real-Time Quantitative PCR for Detection of Helicobacter pylori. by He Q, Wang JP, Osato M, Lachman LB.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130860

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Recombination and mutation during long-term gastric colonization by Helicobacter pylori: Estimates of clock rates, recombination size, and minimal age. by Falush D, Kraft C, Taylor NS, Correa P, Fox JG, Achtman M, Suerbaum S.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64982

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Rectal and Intranasal Immunizations with Recombinant Urease Induce Distinct Local and Serum Immune Responses in Mice and Protect against Helicobacter pylori Infection. by Kleanthous H, Myers GA, Georgakopoulos KM, Tibbitts TJ, Ingrassia JW,

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Gray HL, Ding R, Zhang ZZ, Lei W, Nichols R, Lee CK, Ermak TH, Monath TP.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108285 •

Regional Differences in Metronidazole Resistance and Increasing Clarithromycin Resistance among Helicobacter pylori Isolates from Japan. by Kato M, Yamaoka Y, Kim JJ, Reddy R, Asaka M, Kashima K, Osato MS, El-Zaatari FA, Graham DY, Kwon DH.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90045

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Regional Variation among vacA Alleles of Helicobacter pylori in China. by Wang J, van Doorn LJ, Robinson PA, Ji X, Wang D, Wang Y, Ge L, Telford JL, Crabtree JE.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154746

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Regulation of Ferritin-Mediated Cytoplasmic Iron Storage by the Ferric Uptake Regulator Homolog (Fur) of Helicobacter pylori. by Bereswill S, Greiner S, van Vliet AH, Waidner B, Fassbinder F, Schiltz E, Kusters JG, Kist M.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94726

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Relationship between Helicobacter pylori iceA, cagA, and vacA Status and Clinical Outcome: Studies in Four Different Countries. by Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85136

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Relevance of CagA Positivity to Clinical Course of Helicobacter pylori Infection in Children. by Yahav J, Fradkin A, Weisselberg B, Diver-Haver A, Shmuely H, Jonas A.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87432

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Reliability of Helicobacter pylori and CagA Serological Assays. by Everhart JE, Kruszon-Moran D, Perez-Perez G.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119961

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Responses of Endoscopy Patients in Ladakh, India, to Helicobacter pylori Whole-Cell and CagA Antigens. by Romero-Gallo J, Perez-Perez GI, Novick RP, Kamath P, Norbu T, Blaser MJ.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130106

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Ribotyping of Helicobacter pylori from clinical specimens. by Tee W, Lambert J, Smallwood R, Schembri M, Ross BC, Dwyer B.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265329

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Ribotyping patterns and emergence of metronidazole resistance in paired clinical samples of Helicobacter pylori. by Rautelin H, Tee W, Seppala K, Kosunen TU.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267189

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Rifampin and Rifabutin Resistance Mechanism in Helicobacter pylori. by Heep M, Beck D, Bayerdorffer E, Lehn N.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89306

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Risk of Development of In Vitro Resistance to Amoxicillin, Clarithromycin, and Metronidazole in Helicobacter pylori. by Sorberg M, Hanberger H, Nilsson M, Bjorkman A, Nilsson LE.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105783

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161

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Role of Activated Protein C in Helicobacter pylori-Associated Gastritis. by Oka S, Gabazza EC, Taguchi Y, Yamaguchi M, Nakashima S, Suzuki K, Adachi Y, Imoto I.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97498

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Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis. by Rieder G, Hatz RA, Moran AP, Walz A, Stolte M, Enders G.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175515

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Role of Corpus Gastritis and cagA-Positive Helicobacter pylori Infection in Reflux Esophagitis. by Queiroz DM, Rocha GA, Oliveira CA, Rocha AM, Santos A, Cabral MM, Nogueira AM.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120632

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Role of Gamma Interferon in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model. by Sawai N, Kita M, Kodama T, Tanahashi T, Yamaoka Y, Tagawa YI, Iwakura Y, Imanishi J.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96308

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Role of Helicobacter pylori cag Region Genes in Colonization and Gastritis in Two Animal Models. by Eaton KA, Kersulyte D, Mefford M, Danon SJ, Krakowka S, Berg DE.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98241

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Role of vacA and cagA in Helicobacter pylori Inhibition of Mucin Synthesis in Gastric Mucous Cells. by Beil W, Enss ML, Muller S, Obst B, Sewing KF, Wagner S.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86767

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Roles of FrxA and RdxA Nitroreductases of Helicobacter pylori in Susceptibility and Resistance to Metronidazole. by Jeong JY, Mukhopadhyay AK, Akada JK, Dailidiene D, Hoffman PS, Berg DE.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95392

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Safety and Immunogenicity of Oral Inactivated Whole-Cell Helicobacter pylori Vaccine with Adjuvant among Volunteers with or without Subclinical Infection. by Kotloff KL, Sztein MB, Wasserman SS, Losonsky GA, DiLorenzo SC, Walker RI.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98341

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Sensitive detection of Helicobacter pylori by using polymerase chain reaction. by Clayton CL, Kleanthous H, Coates PJ, Morgan DD, Tabaqchali S.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265019

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Sequence Analysis and Clinical Significance of the iceA Gene from Helicobacter pylori Strains in Japan. by Ito Y, Azuma T, Ito S, Suto H, Miyaji H, Yamazaki Y, Kato T, Kohli Y, Keida Y, Kuriyama M.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86129

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Sequence anomalies in the Cag7 gene of the Helicobacter pylori pathogenicity island. by Liu G, McDaniel TK, Falkow S, Karlin S.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22039

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Sequence-related protein export NTPases encoded by the conjugative transfer region of RP4 and by the cag pathogenicity island of Helicobacter pylori share similar

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hexameric ring structures. by Krause S, Barcena M, Pansegrau W, Lurz R, Carazo JM, Lanka E.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16193 •

Sequencing, expression, and genetic characterization of the Helicobacter pylori ftsH gene encoding a protein homologous to members of a novel putative ATPase family. by Ge Z, Taylor DE.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178484

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Sequential Inactivation of rdxA (HP0954) and frxA (HP0642) Nitroreductase Genes Causes Moderate and High-Level Metronidazole Resistance in Helicobacter pylori. by Jeong JY, Mukhopadhyay AK, Dailidiene D, Wang Y, Velapatino B, Gilman RH, Parkinson AJ, Nair GB, Wong BC, Lam SK, Mistry R, Segal I, Yuan Y, Gao H, Alarcon T, Brea ML, Ito Y, Kersulyte D, Lee HK, Gong Y, Goodwin A, Hoffman PS, Berg DE.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94655

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Serologic detection of infection with cagA+ Helicobacter pylori strains. by Cover TL, Glupczynski Y, Lage AP, Burette A, Tummuru MK, Perez-Perez GI, Blaser MJ.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228203

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Serum Immunoglobulin G Immune Response to Helicobacter pylori Antigens in Mongolian Gerbils. by Kumagai T, Yan J, Graham DY, Tozuka M, Okimura Y, Ikeno T, Sugiyama A, Katsuyama T, Ota H.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87925

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Short-Term Follow-Up by Serology of Patients Given Antibiotic Treatment for Helicobacter pylori Infection. by Laheij RJ, Witteman EM, Bloembergen P, de Koning RW, Jansen JB, Verbeek AL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104798

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Simple and Accurate PCR-Based System for Typing Vacuolating Cytotoxin Alleles of Helicobacter pylori. by Atherton JC, Cover TL, Twells RJ, Morales MR, Hawkey CJ, Blaser MJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85427

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Site-Specific Mutations in the 23S rRNA Gene of Helicobacter pylori Confer Two Types of Resistance to Macrolide-Lincosamide-Streptogramin B Antibiotics. by Wang G, Taylor DE.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105715

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Spontaneous Mutations That Confer Antibiotic Resistance in Helicobacter pylori. by Wang G, Wilson TJ, Jiang Q, Taylor DE.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90364

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Stable and Unstable Amoxicillin Resistance in Helicobacter pylori: Should Antibiotic Resistance Testing Be Performed Prior to Eradication Therapy? by Han SR, Bhakdi S, Maeurer MJ.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85335

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Strain-specific genes of Helicobacter pylori: distribution, function and dynamics. by Janssen PJ, Audit B, Ouzounis CA.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60179

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String Test for Helicobacter pylori. by Perez-Trallero E, Montes M.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87595

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Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. by Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, Talalay P, Lozniewski A.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124299

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Superoxide Dismutase-Deficient Mutants of Helicobacter pylori Are Hypersensitive to Oxidative Stress and Defective in Host Colonization. by Seyler RW Jr, Olson JW, Maier RJ.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98466

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Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis. by Phadnis SH, Parlow MH, Levy M, Ilver D, Caulkins CM, Connors JB, Dunn BE.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173855

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Susceptibility of Helicobacter pylori to bactericidal properties of medium-chain monoglycerides and free fatty acids. by Petschow BW, Batema RP, Ford LL.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163106

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Switching of Flagellar Motility in Helicobacter pylori by Reversible Length Variation of a Short Homopolymeric Sequence Repeat in fliP, a Gene Encoding a Basal Body Protein. by Josenhans C, Eaton KA, Thevenot T, Suerbaum S.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98385

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Systematic Identification of Selective Essential Genes in Helicobacter pylori by Genome Prioritization and Allelic Replacement Mutagenesis. by Chalker AF, Minehart HW, Hughes NJ, Koretke KK, Lonetto MA, Brinkman KK, Warren PV, Lupas A, Stanhope MJ, Brown JR, Hoffman PS.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94999

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The Efficacy of Laboratory Diagnosis of Helicobacter pylori Infections in Gastric Biopsy Specimens Is Related to Bacterial Density and vacA, cagA, and iceA Genotypes. by van Doorn LJ, Henskens Y, Nouhan N, Verschuuren A, Vreede R, Herbink P, Ponjee G, van Krimpen K, Blankenburg R, Scherpenisse J, Quint W.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86006

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The Entner-Doudoroff Pathway Has Little Effect on Helicobacter pylori Colonization of Mice. by Wanken AE, Conway T, Eaton KA.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153294

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The fdxA Ferredoxin Gene Can Down-Regulate frxA Nitroreductase Gene Expression and Is Essential in Many Strains of Helicobacter pylori. by Mukhopadhyay AK, Jeong JY, Dailidiene D, Hoffman PS, Berg DE.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154416

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The GroES Homolog of Helicobacter pylori Confers Protective Immunity Against Mucosal Infection in Mice. by Ferrero RL, Thiberge J, Kansau I, Wuscher N, Huerre M, Labigne A.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41545

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The Helicobacter pylori gene encoding phosphatidylserine synthase: sequence, expression, and insertional mutagenesis. by Ge Z, Taylor DE.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179351

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The Helicobacter pylori genome is modified at CATG by the product of hpyIM. by Xu Q, Peek RM Jr, Miller GG, Blaser MJ.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179612

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The Helicobacter pylori Homologue of the Ferric Uptake Regulator Is Involved in Acid Resistance. by Bijlsma JJ, Waidner B, Vliet AH, Hughes NJ, Hag S, Bereswill S, Kelly DJ, Vandenbroucke-Grauls CM, Kist M, Kusters JG.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127672

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The Helicobacter pylori ureC gene codes for a phosphoglucosamine mutase. by De Reuse H, Labigne A, Mengin-Lecreulx D.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179139

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The Helicobacter pylori UreI Protein Is Not Involved in Urease Activity but Is Essential for Bacterial Survival In Vivo. by Skouloubris S, Thiberge JM, Labigne A, De Reuse H.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108549

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The impact of parietal cells on Helicobacter pylori tropism and host pathology: An analysis using gnotobiotic normal and transgenic mice. by Syder AJ, Oh JD, Guruge JL, O'Donnell D, Karlsson M, Mills JC, Bjorkholm BM, Gordon JI.; 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152316

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The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. by Pagliaccia C, de Bernard M, Lupetti P, Ji X, Burroni D, Cover TL, Papini E, Rappuoli R, Telford JL, Reyrat JM.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21487

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The major sigma factor (RpoD) from Helicobacter pylori and other gram-negative bacteria shows an enhanced rate of divergence. by Solnick JV, Hansen LM, Syvanen M.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179528

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The Morphological Transition of Helicobacter pylori Cells from Spiral to Coccoid Is Preceded by a Substantial Modification of the Cell Wall. by Costa K, Bacher G, Allmaier G, Dominguez-Bello MG, Engstrand L, Falk P, de Pedro MA, Garcia-del Portillo F.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93848

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The Nonfunctional Allele TCRBV6S1B Is Strongly Associated with Helicobacter pylori Infection. by Kunstmann E, Hardt C, Elitok E, Harder M, Suerbaum S, Peitz U, Schmiegel W, Epplen JT.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97740

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The urease enzyme of Helicobacter pylori does not function as an adhesin. by Clyne M, Drumm B.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174146

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165

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Three-Dimensional Quantitative Structure-Activity Relationship and Comparative Molecular Field Analysis of Dipeptide Hydroxamic Acid Helicobacter pylori Urease Inhibitors. by Mishra H, Parrill AL, Williamson JS.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127352

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TraG-Like Proteins of DNA Transfer Systems and of the Helicobacter pylori Type IV Secretion System: Inner Membrane Gate for Exported Substrates? by Schroder G, Krause S, Zechner EL, Traxler B, Yeo HJ, Lurz R, Waksman G, Lanka E.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135038

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Transcriptional Phase Variation of a Type III Restriction-Modification System in Helicobacter pylori. by de Vries N, Duinsbergen D, Kuipers EJ, Pot RG, Wiesenekker P, Penn CW, van Vliet AH, Vandenbroucke-Grauls CM, Kusters JG.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135423

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Transient and persistent experimental infection of nonhuman primates with Helicobacter pylori: implications for human disease. by Dubois A, Berg DE, Incecik ET, Fiala N, Heman-Ackah LM, Perez-Perez GI, Blaser MJ.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174162

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Two Different Families of hopQ Alleles in Helicobacter pylori. by Cao P, Cover TL.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154617

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Two Distinct Antigenic Types of the Polysaccharide Chains of Helicobacter pylori Lipopolysaccharides Characterized by Reactivity with Sera from Humans with Natural Infection. by Yokota SI, Amano KI, Shibata Y, Nakajima M, Suzuki M, Hayashi S, Fujii N, Yokochi T.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97114

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Two Enzyme Immunoassays and PCR for Detection of Helicobacter pylori in Stool Specimens from Pediatric Patients before and after Eradication Therapy. by Makristathis A, Barousch W, Pasching E, Binder C, Kuderna C, Apfalter P, Rotter ML, Hirschl AM.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87461

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Two Predicted Chemoreceptors of Helicobacter pylori Promote Stomach Infection. by Andermann TM, Chen YT, Ottemann KM.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128301

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Two-Component Systems of Helicobacter pylori Contribute to Virulence in a Mouse Infection Model. by Panthel K, Dietz P, Haas R, Beier D.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187308

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Typing of Helicobacter pylori vacA Gene and Detection of cagA Gene by PCR and Reverse Hybridization. by van Doorn LJ, Figueiredo C, Rossau R, Jannes G, van Asbroeck M, Sousa JC, Carneiro F, Quint WG.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104813

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Typing of Helicobacter pylori with monoclonal antibodies against Lewis antigens in lipopolysaccharide. by Simoons-Smit IM, Appelmelk BJ, Verboom T, Negrini R, Penner JL, Aspinall GO, Moran AP, Fei SF, Shi BS, Rudnica W, Savio A, de Graaff J.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229216

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Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. by Stein M, Rappuoli R, Covacci A.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15590

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Unique susceptibility of Helicobacter pylori to simethicone emulsifiers in alimentary therapeutic agents. by Kane AV, Plaut AG.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163146

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Urease Plays an Important Role in the Chemotactic Motility of Helicobacter pylori in a Viscous Environment. by Nakamura H, Yoshiyama H, Takeuchi H, Mizote T, Okita K, Nakazawa T.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108597

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Use of an Amplified-Fragment Length Polymorphism Technique To Fingerprint and Differentiate Isolates of Helicobacter pylori. by Gibson JR, Slater E, Xerry J, Tompkins DS, Owen RJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105166

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Use of Egg Yolk-Derived Immunoglobulin as an Alternative to Antibiotic Treatment for Control of Helicobacter pylori Infection. by Shin JH, Yang M, Nam SW, Kim JT, Myung NH, Bang WG, Roe IH.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120060

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Use of Immunoblot Assay To Define Serum Antibody Patterns Associated with Helicobacter pylori Infection and with H. pylori-Related Ulcers. by Aucher P, Petit ML, Mannant PR, Pezennec L, Babin P, Fauchere JL.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104663

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Use of polymerase chain reaction-amplified Helicobacter pylori urease structural genes for differentiation of isolates. by Foxall PA, Hu LT, Mobley HL.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265146

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Use of serum-specific immunoglobulins A and G for detection of Helicobacter pylori infection in patients with chronic gastritis by immunoblot analysis. by Karvar S, Karch H, Frosch M, Burghardt W, Gross U.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230122

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Utilization of time-kill kinetic methodologies for assessing the bactericidal activities of ampicillin and bismuth, alone and in combination, against Helicobacter pylori in stationary and logarithmic growth phases. by Coudron PE, Stratton CW.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162486

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vacA Genotypes and Genetic Diversity in Clinical Isolates of Helicobacter pylori. by Han SR, Schreiber HJ, Bhakdi S, Loos M, Maeurer MJ.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121350

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vacA Genotypes in Helicobacter pylori Strains Isolated from Children with and without Duodenal Ulcer in Brazil. by De Gusmao VR, Nogueira Mendes E, De Magalhaes Queiroz DM, Aguiar Rocha G, Camargos Rocha AM, Ramadan Ashour AA, Teles Carvalho AS.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87127

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167

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Vaccine-Induced Reduction of Helicobacter pylori Colonization in Mice Is Interleukin-12 Dependent but Gamma Interferon and Inducible Nitric Oxide Synthase Independent. by Garhart CA, Heinzel FP, Czinn SJ, Nedrud JG.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145373

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Vacuolating Cytotoxin of Helicobacter pylori Induces Apoptosis in the Human Gastric Epithelial Cell Line AGS. by Kuck D, Kolmerer B, Iking-Konert C, Krammer PH, Stremmel W, Rudi J.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98603

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Variants of the 3[prime prime or minute] Region of the cagA Gene in Helicobacter pylori Isolates from Patients with Different H. pylori-Associated Diseases. by Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105028

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Vector potential of houseflies (Musca domestica) for Helicobacter pylori. by Grubel P, Hoffman JS, Chong FK, Burstein NA, Mepani C, Cave DR.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229738

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Virulence Genes and Neutral DNA Markers of Helicobacter pylori Isolates from Different Ethnic Communities of West Bengal, India. by Datta S, Chattopadhyay S, Balakrish Nair G, Mukhopadhyay AK, Hembram J, Berg DE, Rani Saha D, Khan A, Santra A, Bhattacharya SK, Chowdhury A.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179778

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Virulence Genes in Helicobacter pylori Strains from West Bengal Residents with Overt H. pylori-Associated Disease and Healthy Volunteers. by Chattopadhyay S, Datta S, Chowdhury A, Chowdhury S, Mukhopadhyay AK, Rajendran K, Bhattacharya SK, Berg DE, Nair GB.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120544

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

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.

168

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A clinical practice viewpoint: to culture or not to culture Helicobacter pylori? Author(s): Zullo A, Hassan C, Lorenzetti R, Winn S, Morini S. Source: Dig Liver Dis. 2003 May; 35(5): 357-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846409

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A coordinated cytotoxic effect of IFN-gamma and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis. Author(s): Itoh T, Yoshida M, Chiba T, Kita T, Wakatsuki Y. Source: Helicobacter. 2003 August; 8(4): 268-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950599

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A novel 13C-urea breath test device for the diagnosis of Helicobacter pylori infection: continuous online measurements allow for faster test results with high accuracy. Author(s): Israeli E, Ilan Y, Meir SB, Buenavida C, Goldin E. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 139-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869884

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A positive assay for identification of cagA negative strains of Helicobacter pylori. Author(s): Sicinschi LA, Correa P, Bravo LE, Schneider BG. Source: Journal of Microbiological Methods. 2003 December; 55(3): 625-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607406

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A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Author(s): Miehlke S, Kirsch C, Schneider-Brachert W, Haferland C, Neumeyer M, Bastlein E, Papke J, Jacobs E, Vieth M, Stolte M, Lehn N, Bayerdorffer E. Source: Helicobacter. 2003 August; 8(4): 310-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950604

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A protocol for isolating putative Helicobacter pylori from fecal specimens and genotyping using vacA alleles. Author(s): Liang S, Redlinger T. Source: Helicobacter. 2003; 8(5): 561-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14536003

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169

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A randomized trial comparing seven-day ranitidine bismuth citrate and clarithromycin dual therapy to seven-day omeprazole, clarithromycin and amoxicillin triple therapy for the eradication of Helicobacter pylori. Author(s): Veldhuyzen van Zanten S, Chiba N, Barkun A, Fallone C, Farley A, Cockeram A, Dallaire C, Simms L, Nicholls B. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 September; 17(9): 533-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532926

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A retrospective study on efficacy of proton-pump inhibitor-based triple therapy for eradication of Helicobacter pylori in patients with chronic renal failure. Author(s): Mak SK, Loo CK, Wong PN, Lo KY, Tong GM, Lam EK, Wong AK. Source: Singapore Med J. 2003 February; 44(2): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14503780

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A role of Helicobacter pylori infection in the development of duodenal ulcer after adult living-related liver transplantation. Author(s): Hosotani Y, Kawanami C, Hasegawa K, Watanabe T, Ito T, Oike F, Kaihara S, Okazaki K, Tanaka K, Chiba T. Source: Transplantation. 2003 August 27; 76(4): 702-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973113

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Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia. Author(s): Veldhuyzen van Zanten S, Fedorak RN, Lambert J, Cohen L, Vanjaka A. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1963-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499772

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Accuracy of magnifying endoscopy with methylene blue in the diagnosis of specialized intestinal metaplasia and short-segment Barrett's esophagus in Japanese patients without Helicobacter pylori infection. Author(s): Yagi K, Nakamura A, Sekine A. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872084

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Acid-adaptive genes of Helicobacter pylori. Author(s): Wen Y, Marcus EA, Matrubutham U, Gleeson MA, Scott DR, Sachs G. Source: Infection and Immunity. 2003 October; 71(10): 5921-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500513

170

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Acquired angioedema and Helicobacter pylori infection in a child. Author(s): Varvarovska J, Sykora J, Stozicky F, Chytra I. Source: European Journal of Pediatrics. 2003 October; 162(10): 707-9. Epub 2003 August 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898238

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Active and inactive gastroesophageal reflux diseases related to Helicobacter pylori therapy. Author(s): Nakajima S, Hattori T. Source: Helicobacter. 2003 August; 8(4): 279-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950600

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An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Author(s): Moayyedi P, Deeks J, Talley NJ, Delaney B, Forman D. Source: The American Journal of Gastroenterology. 2003 December; 98(12): 2621-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687807

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Antibiotic resistance of Helicobacter pylori: a cross-sectional study in consecutive patients, and relation to ethnicity. Author(s): Loffeld RJ, Fijen CA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 July; 9(7): 600-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925098

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Antimicrobial resistance in Helicobacter pylori isolates from children. Author(s): Rerksuppaphol S, Hardikar W, Midolo PD, Ward P. Source: Journal of Paediatrics and Child Health. 2003 July; 39(5): 332-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887661

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Antral glandular atrophy and intestinal metaplasia in children with Helicobacter pylori infection. Author(s): Ozturk Y, Buyukgebiz B, Arslan N, Ozer E. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 July; 37(1): 96-7; Author Reply 97-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827016

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171

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Association of anti-GM1 antibodies but not of anti-cytomegalovirus, Campylobacter jejuni and Helicobacter pylori IgG, with a poor outcome in Guillain-Barre syndrome. Author(s): Annunziata P, Figura N, Galli R, Mugnaini F, Lenzi C. Source: Journal of the Neurological Sciences. 2003 September 15; 213(1-2): 55-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873755

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Atopy, Helicobacter pylori and the hygiene hypothesis. Author(s): Cremonini F, Gasbarrini A. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 635-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840674

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B cell responses in gastric antrum and duodenum following oral inactivated Helicobacter pylori whole cell (HWC) vaccine and LT(R192G) in H pylori seronegative individuals. Author(s): Losonsky GA, Kotloff KL, Walker RI. Source: Vaccine. 2003 January 17; 21(5-6): 562-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531656

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babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. Author(s): Oliveira AG, Santos A, Guerra JB, Rocha GA, Rocha AM, Oliveira CA, Cabral MM, Nogueira AM, Queiroz DM. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3964-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904430

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Beta-lactamase inhibitor enhances Helicobacter pylori eradication rate. Author(s): Ojetti V, Migneco A, Zocco MA, Nista EC, Gasbarrini G, Gasbarrini A. Source: Journal of Internal Medicine. 2004 January; 255(1): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687248

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Better survival of Helicobacter pylori infected patients with early gastric cancer is related to a higher level of Thomsen-Friedenreich antigen-specific antibodies. Author(s): Kurtenkov O, Klaamas K, Sergeyev B, Chuzmarov V, Miljukhina L, Shljapnikova L. Source: Immunological Investigations. 2003 February; 32(1-2): 83-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722944

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Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Author(s): Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 29; 99(22): 14428-33. Epub 2002 Oct 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391297

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Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Author(s): Laine L, Hunt R, El-Zimaity H, Nguyen B, Osato M, Spenard J. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650788

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Bleeding peptic ulcers and presence of Helicobacter pylori by various tests: a casecontrol study. Author(s): Castillo-Rojas G, Ballesteros MA, Ponce de Leon S, Morales-Espinosa R, Cravioto A, Lopez-Vidal Y. Source: European Journal of Gastroenterology & Hepatology. 2002 October; 14(10): 11138. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362102

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Bovine anti-Helicobacter pylori antibodies for oral immunotherapy. Author(s): Casswall TH, Nilsson HO, Bjorck L, Sjostedt S, Xu L, Nord CK, Boren T, Wadstrom T, Hammarstrom L. Source: Scandinavian Journal of Gastroenterology. 2002 December; 37(12): 1380-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523586

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Breath ammonia measurement in Helicobacter pylori infection. Author(s): Kearney DJ, Hubbard T, Putnam D. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2523-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452390

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Breath test is very reliable for diagnosis of Helicobacter pylori infection in real clinical practice. Author(s): Gomollon F, Ducons JA, Santolaria S, Lera Omiste I, Guirao R, Ferrero M, Montoro M. Source: Dig Liver Dis. 2003 September; 35(9): 612-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563182

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173

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Breath test using a single 50-mg dose of 13C-urea to detect Helicobacter pylori infection in children. Author(s): Canete A, Abunaji Y, Alvarez-Calatayud G, DeVicente M, GonzalezHolguera JA, Leralta M, Pajares JM, Gisbert JP. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 January; 36(1): 105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12500004

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Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: recent developments and future implications. Author(s): Rothenbacher D, Brenner H. Source: Microbes and Infection / Institut Pasteur. 2003 July; 5(8): 693-703. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814770

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CagA antibodies as a marker of virulence in chilean patients with Helicobacter pylori infection. Author(s): Harris PR, Godoy A, Arenillas S, Riera F, Garcia D, Einisman H, Pena A, Rollan A, Duarte I, Guiraldes E, Perez-Perez G. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 596602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581804

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Can pre-neoplastic lesions be detected in gastric biopsies of children with Helicobacter pylori infection? Author(s): Guarner J, Bartlett J, Whistler T, Pierce-Smith D, Owens M, Kreh R, Czinn S, Gold BD. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 September; 37(3): 30914. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960654

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Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation. Author(s): Willhite DC, Cover TL, Blanke SR. Source: The Journal of Biological Chemistry. 2003 November 28; 278(48): 48204-9. Epub 2003 September 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129933

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Characterisation of Helicobacter pylori isolates from the north-eastern region of Mexico. Author(s): Garza-Gonzalez E, Bosques-Padilla FJ, Tijerina-Menchaca R, Perez-Perez GI. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2004 January; 10(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706085

174

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Characterization of Helicobacter pylori strainsisolated before and after therapy. Author(s): Andrzejewska E, Szkaradkiewicz A, Klincewicz H, Linke K. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 September; 9(9): Cr400-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960930

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Childhood Helicobacter pylori infection, clinical presentations, endoscopic, histologic features and results of treatment. Author(s): Vithayasai N. Source: J Med Assoc Thai. 2003 August; 86 Suppl 3: S600-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700155

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Chinese literature associated with diagnosis of Helicobacter pylori. Author(s): Wan Y, Xu YY, Jiang JH, Kong FS, Xue FB, Bai YX, Pan BR, Ren J, Fan DM. Source: World Journal of Gastroenterology : Wjg. 2004 January 15; 10(2): 231-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716829

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Clinicopathological features of Meckel's diverticula in 32 patients, with emphasis on the presence of Helicobacter pylori. Author(s): Edge JM, Schneider JW, Moore SW. Source: S Afr J Surg. 2001 August; 39(3): 80-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14601547

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Cloning, expression, purification and properties of a putative multidrug resistance efflux protein from Helicobacter pylori. Author(s): Morrison S, Ward A, Hoyle CJ, Henderson PJ. Source: International Journal of Antimicrobial Agents. 2003 September; 22(3): 242-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678828

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Comparable Helicobacter pylori eradication rates obtained with 4- and 7-day rabeprazole-based triple therapy: a preliminary study. Author(s): Gambaro C, Bilardi C, Dulbecco P, Iiritano E, Zentilin P, Mansia C, Usai P, Vigneri S, Savarino V. Source: Dig Liver Dis. 2003 November; 35(11): 763-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674665

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Comparison of four-day and seven-day pantoprazole-based quadruple therapy as a routine treatment for Helicobacter pylori infection. Author(s): de Boer SY, v d Meeberg PC, Siem H, de Boer WA. Source: The Netherlands Journal of Medicine. 2003 June; 61(6): 218-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956102

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175

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Comparison of genotyping of Helicobacter pylori cagA and vacA virulence genes from gastric biopsies and stool specimens. Author(s): Sicinschi LA, Correa P, Schneider BG. Source: Helicobacter. 2003 December; 8(6): 601-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632675

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Comparison of three stool antigen tests for Helicobacter pylori detection. Author(s): Andrews J, Marsden B, Brown D, Wong VS, Wood E, Kelsey M. Source: Journal of Clinical Pathology. 2003 October; 56(10): 769-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514781

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Compartment theory in Helicobacter pylori-associated gastric carcinogenesis. Author(s): Tseng HH, Hsu PI, Chen HC, Lai KH, Lo GH, Lo CC, Chou NH, Mok KT, Chen IS, Chou NH, Yang HB, Liu L, Hsu PN. Source: Anticancer Res. 2003 July-August; 23(4): 3223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926056

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Concordance of Helicobacter pylori strains within families. Author(s): Kivi M, Tindberg Y, Sorberg M, Casswall TH, Befrits R, Hellstrom PM, Bengtsson C, Engstrand L, Granstrom M. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5604-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662948

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Construction of expression systems for flaA and flaB genes of Helicobacter pylori and determination of immunoreactivity and antigenicity of recombinant proteins. Author(s): Yan J, Liang SH, Mao YF, Li LW, Li SP. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2240-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562386

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Correlation between cag pathogenicity island composition and Helicobacter pyloriassociated gastroduodenal disease. Author(s): Nilsson C, Sillen A, Eriksson L, Strand ML, Enroth H, Normark S, Falk P, Engstrand L. Source: Infection and Immunity. 2003 November; 71(11): 6573-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573679

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Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial. Author(s): Kuipers EJ, Nelis GF, Klinkenberg-Knol EC, Snel P, Goldfain D, Kolkman JJ, Festen HP, Dent J, Zeitoun P, Havu N, Lamm M, Walan A. Source: Gut. 2004 January; 53(1): 12-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684569

176

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Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori. Author(s): Meyer F, Ramanujam KS, Gobert AP, James SP, Wilson KT. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 October 15; 171(8): 3913-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530307

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Cytoskeletal rearrangements in gastric epithelial cells in response to Helicobacter pylori infection. Author(s): Su B, Ceponis PJ, Sherman PM. Source: Journal of Medical Microbiology. 2003 October; 52(Pt 10): 861-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972579

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Deletion of Helicobacter pylori vacuolating cytotoxin gene by introduction of directed mutagenesis. Author(s): Yuan JP, Li T, Shi XD, Hu BY, Yang GZ, Tong SQ, Guo XK. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562387

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Density of Helicobacter pylori may affect the efficacy of eradication therapy and ulcer healing in patients with active duodenal ulcers. Author(s): Lai YC, Wang TH, Huang SH, Yang SS, Wu CH, Chen TK, Lee CL. Source: World Journal of Gastroenterology : Wjg. 2003 July; 9(7): 1537-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854158

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Detection of clarithromycin-resistant Helicobacter pylori in stool samples. Author(s): Fontana C, Favaro M, Pietroiusti A, Pistoia ES, Galante A, Favalli C. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3636-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904368

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Detection of genomic Helicobacter pylori DNA in the blood of patients positive for the infection. Author(s): Dore MP, Realdi G, Sepulveda AR, Graham DY. Source: Dig Liver Dis. 2003 November; 35(11): 839-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674676

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Detection of Helicobacter pylori and its CagA gene in tonsil and adenoid tissues by PCR. Author(s): Cirak MY, Ozdek A, Yilmaz D, Bayiz U, Samim E, Turet S. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 November; 129(11): 1225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623755

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177

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Detection of Helicobacter pylori in gastric mucosa of patients with gastroduodenal diseases by PCR-restriction analysis using the RNA polymerase gene (rpoB). Author(s): Lim CY, Lee KH, Cho MJ, Chang MW, Kim SY, Myong NH, Lee WK, Rhee KH, Kook YH. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3387-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843100

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Detection of Helicobacter pylori in nasal and maxillary sinus specimens from patients with chronic sinusitis. Author(s): Morinaka S, Ichimiya M, Nakamura H. Source: The Laryngoscope. 2003 September; 113(9): 1557-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972933

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Detection of Helicobacter pylori in recurrent aphthous ulceration by nested PCR. Author(s): Iamaroon A, Chaimano S, Linpisarn S, Pongsiriwet S, Phornphutkul K. Source: J Oral Sci. 2003 June; 45(2): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930134

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Detection of high-level tetracycline resistance in clinical isolates of Helicobacter pylori using PCR-RFLP. Author(s): Ribeiro ML, Gerrits MM, Benvengo YH, Berning M, Godoy AP, Kuipers EJ, Mendonca S, van Vliet AH, Pedrazzoli J Jr, Kusters JG. Source: Fems Immunology and Medical Microbiology. 2004 January 15; 40(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734187

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Detection of serum anti-Helicobacter pylori immunoglobulin G in patients with different digestive malignant tumors. Author(s): Wang KX, Wang XF, Peng JL, Cui YB, Wang J, Li CP. Source: World Journal of Gastroenterology : Wjg. 2003 November; 9(11): 2501-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606084

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Determinants of geographic variation in Helicobacter pylori infection among children on the US-Mexico border. Author(s): O'Rourke K, Goodman KJ, Grazioplene M, Redlinger T, Day RS. Source: American Journal of Epidemiology. 2003 October 15; 158(8): 816-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561672

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Diagnosis of Helicobacter pylori infection in adults with intellectual disability. Author(s): Wallace RA, Schluter PJ, Forgan-Smith R, Wood R, Webb PM. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4700-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532206

178

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Diagnosis of Helicobacter pylori infection. Author(s): Rautelin H, Lehours P, Megraud F. Source: Helicobacter. 2003; 8 Suppl 1: 13-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617213

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Diagnostic accuracy of serological kits for Helicobacter pylori infection with the same assay system but different antigens in a Japanese patient population. Author(s): Obata Y, Kikuchi S, Miwa H, Yagyu K, Lin Y, Ogihara A. Source: Journal of Medical Microbiology. 2003 October; 52(Pt 10): 889-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972583

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Diagnostic methods for Helicobacter pylori detection and eradication. Author(s): Goddard AF, Logan RP. Source: British Journal of Clinical Pharmacology. 2003 September; 56(3): 273-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919175

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Distribution of cagG gene in Helicobacter pylori isolates from Chinese patients with different gastroduodenal diseases and its clinical and pathological significance. Author(s): Xu C, Li ZS, Tu ZX, Xu GM, Gong YF, Man XH. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2258-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562388

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Do decision-analytic models identify cost-effective treatments? A retrospective look at helicobacter pylori eradication. Author(s): Fairman KA, Motheral BR. Source: J Manag Care Pharm. 2003 September-October; 9(5): 430-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613441

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Does Helicobacter pylori infection relate to iron deficiency anaemia in prepubescent children under 12 years of age? Author(s): Choi JW. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 August; 92(8): 970-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948075

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Does intragastric nitrite concentration reflect gastric carcinogenesis in Japanese Helicobacter pylori-infected patients? Author(s): Tari A, Kodama K, Sumii M, Tani H, Sumii K, Chayama K. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1730-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560992

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179

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Dyspepsia symptoms and Helicobacter pylori infection, Nakuru, Kenya. Author(s): Shmuely H, Obure S, Passaro DJ, Abuksis G, Yahav J, Fraser G, Pitlik S, Niv Y. Source: Emerging Infectious Diseases. 2003 September; 9(9): 1103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519247

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Effect of Helicobacter pylori eradicated therapy on water gastric emptying in patients with active duodenal ulcer. Author(s): Chang FY, Lu CL, Chen CY, Luo JC, Jium KL, Lee SD. Source: Journal of Gastroenterology and Hepatology. 2003 November; 18(11): 1250-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535981

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Effect of Helicobacter pylori eradication on development of dyspeptic and reflux disease in healthy asymptomatic subjects. Author(s): Vaira D, Vakil N, Rugge M, Gatta L, Ricci C, Menegatti M, Leandro G, Holton J, Russo VM, Miglioli M. Source: Gut. 2003 November; 52(11): 1543-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570720

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Effect of Helicobacter pylori eradication on high-density lipoprotein cholesterol. Author(s): Scharnagl H, Kist M, Grawitz AB, Koenig W, Wieland H, Marz W. Source: The American Journal of Cardiology. 2004 January 15; 93(2): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715353

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Effect of Helicobacter pylori eradication on the treatment of gastro-oesophageal reflux disease. Author(s): Richter JE. Source: Gut. 2004 February; 53(2): 310-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724170

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Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: a double blind, placebo controlled, randomised trial. Author(s): Wu JC, Chan FK, Ching JY, Leung WK, Hui Y, Leong R, Chung SC, Sung JJ. Source: Gut. 2004 February; 53(2): 174-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724146

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Effect of Helicobacter pylori infection in Barrett's esophagus and the genesis of esophageal adenocarcinoma. Author(s): Clark GW. Source: World Journal of Surgery. 2003 September; 27(9): 994-8. Epub 2003 July 24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560364

180

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Effect of Helicobacter pylori infection on expression of Bcl-2 family members in gastric adenocarcinoma. Author(s): Zhang H, Fang DC, Wang RQ, Yang SM, Liu HF, Luo YH. Source: World Journal of Gastroenterology : Wjg. 2004 January 15; 10(2): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716828

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Effect of heparin binding on Helicobacter pylori resistance to serum. Author(s): Dubreuil JD, Ruggiero P, Rappuoli R, Del Giudice G. Source: Journal of Medical Microbiology. 2004 January; 53(Pt 1): 9-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663099

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Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Author(s): Umehara S, Higashi H, Ohnishi N, Asaka M, Hatakeyama M. Source: Oncogene. 2003 November 13; 22(51): 8337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614457

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Efficacy of different antibiotic regimens for eradication treatment of Helicobacter pylori infection in peptic ulcer disease in Tanzanian patients. Author(s): Neuhann HF, Swai B, Carpenter CF, Shao O. Source: Trop Doct. 2003 October; 33(4): 225-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620428

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Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura. Author(s): Jaing TH, Yang CP, Hung IJ, Chiu CH, Chang KW. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 October; 92(10): 1153-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632330

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Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice. Author(s): Haristoy X, Angioi-Duprez K, Duprez A, Lozniewski A. Source: Antimicrobial Agents and Chemotherapy. 2003 December; 47(12): 3982-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638516

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Epidemiology of Helicobacter pylori infection. Author(s): Malaty HM, Nyren O. Source: Helicobacter. 2003; 8 Suppl 1: 8-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617212

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Eradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies. Author(s): Bochenek WJ, Peters S, Fraga PD, Wang W, Mack ME, Osato MS, El-Zimaity HM, Davis KD, Graham DY; Helicobacter pylori Pantoprazole Eradication (HELPPE) Study Group. Source: Helicobacter. 2003 December; 8(6): 626-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632678

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Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer. Author(s): Arkkila PE, Seppala K, Kosunen TU, Haapiainen R, Kivilaakso E, Sipponen P, Makinen J, Nuutinen H, Rautelin H, Farkkila MA. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2149-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572560

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Eradication of Helicobacter pylori infection improves blood pressure values in patients affected by hypertension. Author(s): Migneco A, Ojetti V, Specchia L, Franceschi F, Candelli M, Mettimano M, Montebelli R, Savi L, Gasbarrini G. Source: Helicobacter. 2003 December; 8(6): 585-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632672

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Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma. Author(s): Lehours P, Menard A, Dupouy S, Bergey B, Richy F, Zerbib F, RuskoneFourmestraux A, Delchier JC, Megraud F. Source: Infection and Immunity. 2004 February; 72(2): 880-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742532

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Evidence against the fecal-oral route of transmission for Helicobacter pylori infection in childhood. Author(s): Tosun SY, Kasirga E, Ertan P, Aksu S. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 November; 9(11): Cr489-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586275

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Expression of class I and II MHC receptors in Helicobacter pylori-positive patients with active gastritis and duodenal ulcer. Author(s): Suleymanov Z. Source: Turk J Gastroenterol. 2003 September; 14(3): 168-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655059

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Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Author(s): Hase K, Murakami M, Iimura M, Cole SP, Horibe Y, Ohtake T, Obonyo M, Gallo RL, Eckmann L, Kagnoff MF. Source: Gastroenterology. 2003 December; 125(6): 1613-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724813

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Factors associated with treatment failure of Helicobacter pylori infection in a developing country. Author(s): Queiroz DM, Dani R, Silva LD, Santos A, Moreira LS, Rocha GA, Correa PR, Reis LF, Nogueira AM, Alvares Cabral MM, Esteves AM, Tanure J. Source: Journal of Clinical Gastroenterology. 2002 October; 35(4): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352294

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Factors contributing to the development of gastric cancer due to Helicobacter pylori infection. Author(s): Chiba T. Source: Current Gastroenterology Reports. 2002 August; 4(4): 267-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149167

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Family history of gastric cancer: should we test and treat for Helicobacter pylori? Author(s): Niv Y. Source: Journal of Clinical Gastroenterology. 2003 March; 36(3): 204-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590229

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Fast and accurate quantitative detection of Helicobacter pylori and identification of clarithromycin resistance mutations in H. pylori isolates from gastric biopsy specimens by real-time PCR. Author(s): Lascols C, Lamarque D, Costa JM, Copie-Bergman C, Le Glaunec JM, Deforges L, Soussy CJ, Petit JC, Delchier JC, Tankovic J. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4573-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532184

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Favourable effect of regular intake of fermented milk containing Lactobacillus johnsonii on Helicobacter pylori associated gastritis. Author(s): Pantoflickova D, Corthesy-Theulaz I, Dorta G, Stolte M, Isler P, Rochat F, Enslen M, Blum AL. Source: Alimentary Pharmacology & Therapeutics. 2003 October 15; 18(8): 805-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535874

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Features of chronic inflammation at the gastric cardia and the relationship with Helicobacter pylori infection and oesophagitis. Author(s): Ayhan S, Demir MA, Kandiloglu AR, Saruc M, Kucukmetin N. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 144-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891923

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Fine-structure molecular typing of Irish Helicobacter pylori isolates and their genetic relatedness to strains from four different continents. Author(s): Carroll IM, Ahmed N, Beesley SM, Khan AA, Ghousunnissa S, Morain CA, Smyth CJ. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5755-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662976

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Five minute endoscopic urea breath test with 25 mg of (13)C-urea in the management of Helicobacter pylori infection. Author(s): Isomoto H, Inoue K, Shikuwa S, Furusu H, Nishiyama T, Omagari K, Mizuta Y, Murase K, Murata I, Enjoji A, Kanematsu T, Kohno S. Source: European Journal of Gastroenterology & Hepatology. 2002 October; 14(10): 1093100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362100

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Five years of complete remission of gastric diffuse large B cell lymphoma after eradication of Helicobacter pylori infection. Author(s): Alsolaiman MM, Bakis G, Nazeer T, MacDermott RP, Balint JA. Source: Gut. 2003 April; 52(4): 507-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631659

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Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance of Helicobacter pylori. Author(s): Umamaheswari RB, Jain S, Tripathi PK, Agrawal GP, Jain NK. Source: Drug Delivery. 2002 October-December; 9(4): 223-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511200

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Flow cytometric measurement of tumor necrosis factor-related apoptosis-inducing ligand and its receptors in gastric epithelium and infiltrating mucosal lymphocytes in Helicobacter pylori-associated gastritis. Author(s): Koyama S. Source: Journal of Gastroenterology and Hepatology. 2003 July; 18(7): 763-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12795746

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Fluorescence in situ hybridization vs. epsilometer test for detection of clarithromycinsusceptible and clarithromycin-resistant Helicobacter pylori strains in gastric biopsies from children. Author(s): Feydt-Schmidt A, Russmann H, Lehn N, Fischer A, Antoni I, Stork D, Koletzko S. Source: Alimentary Pharmacology & Therapeutics. 2002 December; 16(12): 2073-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452940

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Foetal intrauterine growth restrictions with Helicobacter pylori infection. Author(s): Eslick GD, Yan P, Xia HH, Murray H, Spurrett B, Talley NJ. Source: Alimentary Pharmacology & Therapeutics. 2002 September; 16(9): 1677-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12197848

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Folk yoghurt kills Helicobacter pylori. Author(s): Oh Y, Osato MS, Han X, Bennett G, Hong WK. Source: Journal of Applied Microbiology. 2002; 93(6): 1083-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452966

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Follicular gastritis associated with Helicobacter pylori. Author(s): Ma ZQ, Tanizawa T, Nihei Z, Sugihara K, Nakamura K. Source: J Med Dent Sci. 2000 March; 47(1): 39-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162525

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Follow-up survey of a large-scale multicenter, double-blind study of triple therapy with lansoprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients. Author(s): Asaka M, Kato M, Sugiyama T, Satoh K, Kuwayama H, Fukuda Y, Fujioka T, Takemoto T, Kimura K, Shimoyama T, Shimizu K, Kobayashi S; Japan Helicobacter pylori Eradication Study Group. Source: Journal of Gastroenterology. 2003; 38(4): 339-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743773

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Food/nutrient intake and risk of atrophic gastritis among the Helicobacter pyloriinfected population of northeastern Japan. Author(s): Montani A, Sasazuki S, Inoue M, Higuchi K, Arakawa T, Tsugane S. Source: Cancer Science. 2003 April; 94(4): 372-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824907

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Frequency of Helicobacter pylori in gastric intestinal metaplasia. Author(s): Hussainy AS, Malik A, Abid F. Source: Indian J Gastroenterol. 2002 July-August; 21(4): 167-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385557

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Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer. Author(s): Backert S, Schwarz T, Miehlke S, Kirsch C, Sommer C, Kwok T, Gerhard M, Goebel UB, Lehn N, Koenig W, Meyer TF. Source: Infection and Immunity. 2004 February; 72(2): 1043-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742552

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Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey. Author(s): Saruc M, Ozden N, Turkel N, Ayhan S, Demir MA, Tuzcuoglu I, Akarca US, Yuceyar H. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 June; 36(6): 747-51. Epub 2003 June 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792704

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Gastric carcinogenesis and Helicobacter pylori infection. Author(s): Pajares Garcia JM, Gisbert JP. Source: Rev Esp Enferm Dig. 2003 February; 95(2): 84-88, 79-83. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760716

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Gastric fundic gland polyps in south-east Scotland: absence of adenomatous polyposis coli gene mutations and a strikingly low prevalence of Helicobacter pylori infection. Author(s): Shand AG, Taylor AC, Banerjee M, Lessels A, Coia J, Clark C, Haites N, Ghosh S. Source: Journal of Gastroenterology and Hepatology. 2002 November; 17(11): 1161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453274

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Gastric inflammatory fibroid polyp treated with Helicobacter pylori eradication therapy. Author(s): Nishiyama Y, Koyama S, Andoh A, Kishi Y, Yoshikawa K, Ishizuka I, Yokono T, Fujiyama Y. Source: Intern Med. 2003 March; 42(3): 263-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705792

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Gastric mucosal cytokine and epithelial cell responses to Helicobacter pylori infection in Mongolian gerbils. Author(s): Crabtree JE, Court M, Aboshkiwa MA, Jeremy AH, Dixon MF, Robinson PA. Source: The Journal of Pathology. 2004 February; 202(2): 197-207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14743502

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Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load. Author(s): Holck S, Norgaard A, Bennedsen M, Permin H, Norn S, Andersen LP. Source: Fems Immunology and Medical Microbiology. 2003 May 25; 36(3): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738388

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Gastric mucosal recognition of Helicobacter pylori is independent of Toll-like receptor 4. Author(s): Backhed F, Rokbi B, Torstensson E, Zhao Y, Nilsson C, Seguin D, Normark S, Buchan AM, Richter-Dahlfors A. Source: The Journal of Infectious Diseases. 2003 March 1; 187(5): 829-36. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599057

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Gastric mucosal response to Helicobacter pylori. Author(s): Suzuki H, Masaoka T, Miyazawa M, Suzuki M, Miura S, Ishii H. Source: The Keio Journal of Medicine. 2002 December; 51 Suppl 2: 40-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528936

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Gastric tube cancer after esophagectomy for esophageal squamous cell cancer and its relevance to Helicobacter pylori. Author(s): Kise Y, Kijima H, Shimada H, Tanaka H, Kenmochi T, Chino O, Tajima T, Makuuchi H. Source: Hepatogastroenterology. 2003 March-April; 50(50): 408-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749234

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Gastroduodenal Helicobacter pylori infection diagnosed by Helicobacter pylori stool antigen is related to atherosclerosis. Author(s): Adiloglu AK, Nazli C, Cicioglu-Aridogan B, Kinay O, Can R, Ergene O. Source: Acta Cardiol. 2003 August; 58(4): 335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948039

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Gastroesophageal reflux disease and Helicobacter pylori infection. Author(s): Vakil N. Source: Reviews in Gastroenterological Disorders. 2003 Winter; 3(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684588

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Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy. Author(s): Konturek PC, Rembiasz K, Konturek SJ, Stachura J, Bielanski W, Galuschka K, Karcz D, Hahn EG. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 36-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645788

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Gene methylation in non-neoplastic mucosa of gastric cancer: age or Helicobacter pylori related? Author(s): Chan AO, Lam SK, Wong BC, Kwong YL, Rashid A. Source: American Journal of Pathology. 2003 July; 163(1): 370-1; Author Reply 371-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819044

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Genomewide linkage analysis identifies polymorphism in the human interferongamma receptor affecting Helicobacter pylori infection. Author(s): Thye T, Burchard GD, Nilius M, Muller-Myhsok B, Horstmann RD. Source: American Journal of Human Genetics. 2003 February; 72(2): 448-53. Epub 2003 January 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516030

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Genomic fingerprinting and genotyping of Helicobacter pylori strains from patients with duodenal ulcer or gastric cancer from different geographic regions. Author(s): Li L, Graham DY, Gutierrez O, Kim JG, Genta RM, El-Zimaity HM, Go MF. Source: Digestive Diseases and Sciences. 2002 November; 47(11): 2512-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452388

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Genotypes of Helicobacter pylori in children with upper abdominal pain. Author(s): Singh M, Prasad KN, Yachha SK, Krishnani N. Source: Journal of Gastroenterology and Hepatology. 2003 September; 18(9): 1018-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911656

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Genotyping of Nigerian Helicobacter pylori isolates by pulsed-field gel electrophoresis. Author(s): Smith SI, Luck PC, Bayerdoffer E, Miehlke S. Source: Journal of Medical Microbiology. 2003 October; 52(Pt 10): 931. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972591

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Ghrelin and Helicobacter pylori. Author(s): Murray CD, Emmanuel AV. Source: Gut. 2004 February; 53(2): 315; Author Reply 315. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724174

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Global regulation of virulence and the stress response by CsrA in the highly adapted human gastric pathogen Helicobacter pylori. Author(s): Barnard FM, Loughlin MF, Fainberg HP, Messenger MP, Ussery DW, Williams P, Jenks PJ. Source: Molecular Microbiology. 2004 January; 51(1): 15-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651608

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Grb2 is a key mediator of helicobacter pylori CagA protein activities. Author(s): Mimuro H, Suzuki T, Tanaka J, Asahi M, Haas R, Sasakawa C. Source: Molecular Cell. 2002 October; 10(4): 745-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419219

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Growth cycle of Helicobacter pylori in gastric mucous layer. Author(s): Nakazawa T. Source: The Keio Journal of Medicine. 2002 December; 51 Suppl 2: 15-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528930

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Healing of Helicobacter pylori gastric ulcers: only eradication matters. Author(s): Bermejo F, Boixeda D, Martin De Argila C, Lopez San Roman A, Defarges V, Hernandez Ranz H, Vazquez M, Garcia Plaza A. Source: Rev Esp Enferm Dig. 2003 September; 95(9): 625-8, 621-4. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738407

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Helicobacter pylori and cagA and vacA gene status in children from Brazil with chronic gastritis. Author(s): Lobo Gatti L, Agostinho Jn F, De Labio R, Balbo Piason F, Carlos Da Silva L, Fagundez De Queiroz V, Peres CA, Barbieri D, De Arruda Cardoso Smith M, Marques Payao SL. Source: Clinical and Experimental Medicine. 2003 November; 3(3): 166-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648232

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Helicobacter pylori and gastric diseases. Author(s): Goto H. Source: Nagoya J Med Sci. 2003 November; 66(3-4): 77-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727684

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Helicobacter pylori and gastroesophageal reflux disease. Author(s): Garrido Serrano A, Lepe Jimenez JA, Guerrero Igea FJ, Perianes Hernandez C. Source: Rev Esp Enferm Dig. 2003 November; 95(11): 788-90, 785-7. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640876

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Helicobacter pylori and glaucoma. Author(s): Kountouras J, Zavos C, Chatzopoulos D. Source: Ophthalmology. 2003 December; 110(12): 2433-4; Author Reply 2434. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644740

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Helicobacter pylori CagA seropositivity is not strongly associated with lichen planus. Author(s): Dauden E, Cabrera MM, Onate MJ, Pajares JM, Garcia-Diez A. Source: Journal of the American Academy of Dermatology. 2003 December; 49(6): 1199. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639425

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Helicobacter pylori colonization in dental plaque and gastric infection. Author(s): Nasrolahei M, Maleki I, Emadian O. Source: Rom J Gastroenterol. 2003 December; 12(4): 293-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726974

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Helicobacter pylori disrupts STAT1-mediated gamma interferon-induced signal transduction in epithelial cells. Author(s): Mitchell DJ, Huynh HQ, Ceponis PJ, Jones NL, Sherman PM. Source: Infection and Immunity. 2004 January; 72(1): 537-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688135

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Helicobacter pylori eradication does not exacerbate gastro-oesophageal reflux disease. Author(s): Malfertheiner P. Source: Gut. 2004 February; 53(2): 312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724171

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Helicobacter pylori eradication down-regulates matrix metalloproteinase-9 expression in chronic gastritis and gastric ulcer. Author(s): Danese S, Papa A, Gasbarrini A, Ricci R, Maggiano N. Source: Gastroenterology. 2004 January; 126(1): 369-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753215

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Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. Author(s): Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK, Chen JS; China Gastric Cancer Study Group. Source: Jama : the Journal of the American Medical Association. 2004 January 14; 291(2): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722144

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Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation. Author(s): Yanai A, Hirata Y, Mitsuno Y, Maeda S, Shibata W, Akanuma M, Yoshida H, Kawabe T, Omata M. Source: The Journal of Infectious Diseases. 2003 December 1; 188(11): 1741-51. Epub 2003 November 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639546

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Helicobacter pylori infection and gastric cancer--for want of more outcomes. Author(s): Parsonnet J, Forman D. Source: Jama : the Journal of the American Medical Association. 2004 January 14; 291(2): 244-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722152

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Helicobacter pylori infection and idiopathic epilepsy. Author(s): Okuda M, Miyashiro E, Nakazawa T, Minami K, Koike M. Source: The American Journal of Medicine. 2004 February 1; 116(3): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749171

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Helicobacter pylori infection and long term proton pump inhibitor therapy. Author(s): McColl KE. Source: Gut. 2004 January; 53(1): 5-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684566

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Helicobacter pylori infection in patients with inflammatory bowel disease. Author(s): Guslandi M. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2570-1; Author Reply 2571-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638369

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Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in Mongolian gerbils. Author(s): Suzuki H, Masaoka T, Hosoda H, Ota T, Minegishi Y, Nomura S, Kangawa K, Ishii H. Source: Gut. 2004 February; 53(2): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724148

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Helicobacter pylori, ghrelin, and obesity. Author(s): Macadam RC, Borse V, Dodo I, Pollard SG. Source: Gut. 2004 February; 53(2): 315-6; Author Reply 316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724173

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Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status. Author(s): Rittig MG, Shaw B, Letley DP, Thomas RJ, Argent RH, Atherton JC. Source: Cellular Microbiology. 2003 December; 5(12): 887-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641174

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High rates of recurrence and of transient reinfections of Helicobacter pylori in a population with high prevalence of infection. Author(s): Leal-Herrera Y, Torres J, Monath TP, Ramos I, Gomez A, Madrazo-de la Garza A, Dehesa-Violante M, Munoz O. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2395-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638339

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Identification of candidate antigens for serologic detection of Helicobacter pyloriinfected patients with gastric carcinoma. Author(s): Krah A, Miehlke S, Pleissner KP, Zimny-Arndt U, Kirsch C, Lehn N, Meyer TF, Jungblut PR, Aebischer T. Source: International Journal of Cancer. Journal International Du Cancer. 2004 January 20; 108(3): 456-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648714

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IgG subclass response to Helicobacter pylori and CagA antigens in children. Author(s): Dzierzanowska-Fangrat K, Raeiszadeh M, Dzierzanowska D, GladkowskaDura M, Celinska-Cedro D, Crabtree JE. Source: Clinical and Experimental Immunology. 2003 December; 134(3): 442-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632749

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Immune response in Helicobacter pylori-induced low-grade gastric-mucosaassociated lymphoid tissue (MALT) lymphoma. Author(s): Yamasaki R, Yokota K, Okada H, Hayashi S, Mizuno M, Yoshino T, Hirai Y, Saitou D, Akagi T, Oguma K. Source: Journal of Medical Microbiology. 2004 January; 53(Pt 1): 21-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663101

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Immunohistochemical testing for Helicobacter pylori infection in ascending aortic aneurysms and penetrating aortic ulcers. Author(s): Koullias GJ, Korkolis DP, Hatzaras IS, Elefteriades JA, Jain D. Source: The American Journal of Cardiology. 2004 January 1; 93(1): 122-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697486

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Immunosuppressive and proinflammatory activities of the VacA toxin of Helicobacter pylori. Author(s): Montecucco C, de Bernard M. Source: The Journal of Experimental Medicine. 2003 December 15; 198(12): 1767-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676291

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Impact of Helicobacter pylori infection on growth of children: a prospective cohort study. Author(s): Bravo LE, Mera R, Reina JC, Pradilla A, Alzate A, Fontham E, Correa P. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 6149. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581807

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Impact of migration on Helicobacter pylori seroprevalence in the offspring of Turkish immigrants in Germany. Author(s): Porsch-Ozcurumez M, Doppl W, Hardt PD, Schnell-Kretschmer H, Tuncay M, Akinci A, Bilgin Y, Klor HU. Source: Turk J Pediatr. 2003 July-September; 45(3): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696797

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In vitro evaluation of Bacopa monniera on anti-Helicobacter pylori activity and accumulation of prostaglandins. Author(s): Goel RK, Sairam K, Babu MD, Tavares IA, Raman A. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10(6-7): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678238

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Increased levels of Helicobacter pylori IgG antibodies in aqueous humor of patients with primary open-angle and exfoliation glaucoma. Author(s): Kountouras J, Mylopoulos N, Konstas AG, Zavos C, Chatzopoulos D, Boukla A. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 November; 241(11): 884-90. Epub 2003 October 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576945

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Induced Helicobacter pylori vacuolating cytotoxin VacA expression after initial colonisation of human gastric epithelial cells. Author(s): van Amsterdam K, van Vliet AH, Kusters JG, Feller M, Dankert J, van der Ende A. Source: Fems Immunology and Medical Microbiology. 2003 December 5; 39(3): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642310

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Induction of cyclooxygenase 2 by Escherichia coli but not Helicobacter pylori lipopolysaccharide in gastric epithelial cells in vitro. Author(s): Smith GV, Moran AP, Bajaj-Elliott M, Farthing MJ. Source: Helicobacter. 2003; 8(5): 513-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535998

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Infection with cagA-positive and cagA-negative types of Helicobacter pylori among children and adolescents with gastrointestinal symptoms in Latvia. Author(s): Daugule I, Rumba I, Engstrand L, Ejderhamn J. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 October; 22(10): 6224. Epub 2003 September 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508659

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Influence of Helicobacter pylori eradication on gastroesophageal reflux symptoms and epigastric pain in children and adolescents. Author(s): Levine A, Milo T, Broide E, Wine E, Dalal I, Boaz M, Avni Y, Shirin H. Source: Pediatrics. 2004 January; 113(1 Pt 1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702447

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Influence of transport conditions and media on Helicobacter pylori isolation. Author(s): Boyanova L. Source: Journal of Medical Microbiology. 2003 December; 52(Pt 12): 1129-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614073

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Inhibition of Helicobacter pylori-induced nuclear factor-kappa B activation and interleukin-8 gene expression by ecabet sodium in gastric epithelial cells. Author(s): Kim JM, Kim JS, Jung HC, Oh YK, Kim N, Song IS. Source: Helicobacter. 2003; 8(5): 542-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14536001

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Intensity of inflammation, density of colonization and interleukin-8 response in the gastric mucosa of children infected with Helicobacter pylori. Author(s): Camorlinga-Ponce M, Aviles-Jimenez F, Cabrera L, Hernandez-Pando R, Munoz O, Soza J, Torres J. Source: Helicobacter. 2003; 8(5): 554-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14536002

194

Helicobacter pylori

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Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection. Author(s): Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Inaba T, Yamamoto K, Okada H, Yokota K, Oguma K, Shiratori Y. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638340

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Interobserver variation in histopathological assessment of Helicobacter pylori gastritis. Author(s): Aydin O, Egilmez R, Karabacak T, Kanik A. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2232-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562384

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Intestinal metaplasia: evolution after Helicobacter pylori eradication and influence in the success of eradicating therapy. Author(s): Vazquez Romero M, Boixeda de Miquel D, Valer Lopez-Fando MP, Albeniz Arbizu E, Gonzalez Alonso R, Bermejo San Jose F. Source: Rev Esp Enferm Dig. 2003 November; 95(11): 781-4, 777-80. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640875

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Is Helicobacter pylori infection a necessary condition for noncardia gastric cancer? Author(s): Brenner H, Arndt V, Stegmaier C, Ziegler H, Rothenbacher D. Source: American Journal of Epidemiology. 2004 February 1; 159(3): 252-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742285

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Kang wei granules in treatment of gastropathy related to Helicobacter pylori infection. Author(s): Chen F, Wei B, Yao W, Luo X. Source: J Tradit Chin Med. 2003 March; 23(1): 27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747192

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Knowledge, attitudes, and practice styles of North American pediatric gastroenterologists: Helicobacter pylori infection. Author(s): Chang HY, Sharma VK, Howden CW, Gold BD. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 February; 36(2): 23540. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548060

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Lack of accuracy of the noninvasive Helicobacter pylori stool antigen test in patients with gastroduodenal ulcer bleeding. Author(s): van Leerdam ME, van der Ende A, ten Kate FJ, Rauws EA, Tytgat GN. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 798-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738458

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Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese. Author(s): Hamajima N, Shibata A, Ikehara Y, Katsuda N, Mori S, Ito H, Matsuo K, Tajima K, Tominaga S. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2002; 5(4): 194-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491076

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Lack of evidence for fecal-oral transmission of Helicobacter pylori infection in Taiwanese. Author(s): Yang YJ, Wang SM, Chen CT, Huang MC, Chang CJ, Liu CC. Source: J Formos Med Assoc. 2003 June; 102(6): 375-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923589

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Lafutidine, a novel histamine H2-receptor antagonist, vs lansoprazole in combination with amoxicillin and clarithromycin for eradication of Helicobacter pylori. Author(s): Isomoto H, Inoue K, Furusu H, Nishiyama H, Shikuwa S, Omagari K, Mizuta Y, Murase K, Murata I, Kohno S. Source: Helicobacter. 2003 April; 8(2): 111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12662378

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Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti-inflammatory drug users--a randomized trial. Author(s): Lai KC, Lam SK, Chu KM, Hui WM, Kwok KF, Wong BC, Hu HC, Wong WM, Chan OO, Chan CK. Source: Alimentary Pharmacology & Therapeutics. 2003 October 15; 18(8): 829-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535877

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Levofloxacin based triple therapy as a second-line treatment after failure of helicobacter pylori eradication with standard triple therapy. Author(s): Watanabe Y, Aoyama N, Shirasaka D, Maekawa S, Kuroda K, Miki I, Kachi M, Fukuda M, Wambura C, Tamura T, Kasuga M. Source: Dig Liver Dis. 2003 October; 35(10): 711-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620620

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Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial. Author(s): Nista EC, Candelli M, Cremonini F, Cazzato IA, Di Caro S, Gabrielli M, Santarelli L, Zocco MA, Ojetti V, Carloni E, Cammarota G, Gasbarrini G, Gasbarrini A. Source: Alimentary Pharmacology & Therapeutics. 2003 September 15; 18(6): 627-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969089

196

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Limited role of lipopolysaccharide Lewis antigens in adherence of Helicobacter pylori to the human gastric epithelium. Author(s): Mahdavi J, Boren T, Vandenbroucke-Grauls C, Appelmelk BJ. Source: Infection and Immunity. 2003 May; 71(5): 2876-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704161

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Lipid peroxidation in chronic gastritis; any influence of Helicobacter pylori? Author(s): Giamarellos-Bourboulis EJ, Tzivras M, Kourtesas D, Arnaoutis TP, Delladatsima I, Dionyssiou-Asteriou A, Davaris P, Vafiadis-Zouboulis I, Archimandritis A. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 April; 68(4): 25761. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628220

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Localization of antigen-presenting cells in Helicobacter pylori-infected gastric mucosa. Author(s): Suzuki T, Kato K, Ohara S, Noguchi K, Sekine H, Nagura H, Shimosegawa T. Source: Pathology International. 2002 April; 52(4): 265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031081

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Long term follow up of Helicobacter pylori induced gastric diffuse large B cell MALT lymphoma following eradication treatment alone. Author(s): Sinharay R. Source: Gut. 2003 September; 52(9): 1385. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912879

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Long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) following exclusive Helicobacter pylori eradication therapy: experience from a large prospective series. Author(s): Fischbach W, Goebeler-Kolve ME, Dragosics B, Greiner A, Stolte M. Source: Gut. 2004 January; 53(1): 34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684573

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Long-term follow-up of gastric metaplasia after eradication of Helicobacter pylori. Author(s): Urakami Y, Sano T. Source: J Med Invest. 2003 February; 50(1-2): 48-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630568

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Long-term observation of reflux oesophagitis developing after Helicobacter pylori eradication therapy. Author(s): Sasaki A, Haruma K, Manabe N, Tanaka S, Yoshihara M, Chayama K. Source: Alimentary Pharmacology & Therapeutics. 2003 June 15; 17(12): 1529-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823156

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197

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Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori. Author(s): Sjolund M, Wreiber K, Andersson DI, Blaser MJ, Engstrand L. Source: Annals of Internal Medicine. 2003 September 16; 139(6): 483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679325

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Low and high doses of rabeprazole vs. omeprazole for cure of Helicobacter pylori infection. Author(s): Kositchaiwat C, Ovartlarnporn B, Kachintorn U, Atisook K. Source: Alimentary Pharmacology & Therapeutics. 2003 November 15; 18(10): 1017-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616168

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Low dose, one-week triple therapy (lanzoprazole, amoxycillin, clarithromycin) for eradication of Helicobacter pylori infection. Author(s): Uthaisaengsook W. Source: J Med Assoc Thai. 2003 July; 86(7): 599-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948252

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Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an Iranian population. Author(s): Malekzadeh R, Merat S, Derakhshan MH, Siavoshi F, Yazdanbod A, Mikaeli J, Sotoudemanesh R, Sotoudeh M, Farahvash MJ, Nasseri-Moghaddam S, Pourshams A, Dolatshahi S, Abedi B, Babaei M, Arshi S, Majidpour A. Source: Journal of Gastroenterology and Hepatology. 2003 January; 18(1): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519218

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Low molecular weight protein of Helicobacter pylori and its relation to gastroduodenal diseases. Author(s): Kuo CH, Wu DC, Lu CY, Su YC, Yu FJ, Lee YC, Wu IC, Lin SR, Liu CS, Jan CM, Wang WM. Source: Hepatogastroenterology. 2003 July-August; 50(52): 897-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845945

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L-Serine, D- and L-proline and alanine as respiratory substrates of Helicobacter pylori: correlation between in vitro and in vivo amino acid levels. Author(s): Nagata K, Nagata Y, Sato T, Fujino MA, Nakajima K, Tamura T. Source: Microbiology (Reading, England). 2003 August; 149(Pt 8): 2023-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904542

198

Helicobacter pylori

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Maintenance treatment is not necessary after Helicobacter pylori eradication and healing of bleeding peptic ulcer: a 5-year prospective, randomized, controlled study. Author(s): Liu CC, Lee CL, Chan CC, Tu TC, Liao CC, Wu CH, Chen TK. Source: Archives of Internal Medicine. 2003 September 22; 163(17): 2020-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504114

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Mastic gum has no effect on Helicobacter pylori load in vivo. Author(s): Bebb JR, Bailey-Flitter N, Ala'Aldeen D, Atherton JC. Source: The Journal of Antimicrobial Chemotherapy. 2003 September; 52(3): 522-3. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888582

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Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication. Author(s): Vergara M, Vallve M, Gisbert JP, Calvet X. Source: Alimentary Pharmacology & Therapeutics. 2003 September 15; 18(6): 647-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969092

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Meta-analysis: proton pump inhibitors vs. H2-receptor antagonists--their efficacy with antibiotics in Helicobacter pylori eradication. Author(s): Gisbert JP, Khorrami S, Calvet X, Gabriel R, Carballo F, Pajares JM. Source: Alimentary Pharmacology & Therapeutics. 2003 October 15; 18(8): 757-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535868

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Meta-analysis: the relationship between Helicobacter pylori infection and gastrooesophageal reflux disease. Author(s): Cremonini F, Di Caro S, Delgado-Aros S, Sepulveda A, Gasbarrini G, Gasbarrini A, Camilleri M. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 279-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895212

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Metronidazole-resistant Helicobacter pylori is more prevalent in patients with nonulcer dyspepsia than in peptic ulcer patients in a multiethnic Asian population. Author(s): Lui SY, Yeoh KG, Ho B. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5011-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605132

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Micropneumatosis coexistent with Helicobacter pylori and its improvement. Author(s): Belenli OK, Akcan Y, Alper M. Source: Indian J Gastroenterol. 2003 September-October; 22(5): 191-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658539

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199

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Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Author(s): Montecucco C, de Bernard M. Source: Microbes and Infection / Institut Pasteur. 2003 July; 5(8): 715-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814772

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Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity. Author(s): Amedei A, Bergman MP, Appelmelk BJ, Azzurri A, Benagiano M, Tamburini C, van der Zee R, Telford JL, Vandenbroucke-Grauls CM, D'Elios MM, Del Prete G. Source: The Journal of Experimental Medicine. 2003 October 20; 198(8): 1147-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568977

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Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Author(s): Takahashi T, Yujiri T, Shinohara K, Inoue Y, Sato Y, Fujii Y, Okubo M, Zaitsu Y, Ariyoshi K, Nakamura Y, Nawata R, Oka Y, Shirai M, Tanizawa Y. Source: British Journal of Haematology. 2004 January; 124(1): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675413

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Molecular typing of Nigerian Helicobacter pylori isolates by glmM restriction fragment length polymorphism. Author(s): Smith SI, Chibututu C, Anomneze E, Atimomo C, Atoyebi O, Ndububa D, Agbakwuru A, Bayerdoffer E, Miehlke S. Source: British Journal of Biomedical Science. 2003; 60(3): 170-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560798

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Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells. Author(s): Futagami S, Hiratsuka T, Tatsuguchi A, Suzuki K, Kusunoki M, Shinji Y, Shinoki K, Iizumi T, Akamatsu T, Nishigaki H, Wada K, Miyake K, Gudis K, Tsukui T, Sakamoto C. Source: Gut. 2003 September; 52(9): 1257-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912855

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Morphologic criteria using biopsy specimens to define the risk of gastric cancer in patients with Helicobacter pylori infection. Author(s): Fukuda S, Tanaka M, Shimoyama T, Sawaya M, Nakaji S, Munakata A. Source: Japanese Journal of Clinical Oncology. 2003 August; 33(8): 396-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523059

200

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Motion--Helicobacter pylori causes or worsens GERD: arguments against the motion. Author(s): McColl KE. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 September; 16(9): 615-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362216

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Motion--Helicobacter pylori worsens GERD: arguments for the motion. Author(s): O'Morain CA, Qasim A. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 September; 16(9): 611-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362215

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Mucolytics and Helicobacter pylori eradication. Author(s): Guslandi M. Source: Helicobacter. 2003 February; 8(1): 79; Author Reply 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603620

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Natural acquisition of Helicobacter pylori infection in newborn rhesus macaques. Author(s): Solnick JV, Chang K, Canfield DR, Parsonnet J. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5511-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662932

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Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study. Author(s): Guttner Y, Windsor HM, Viiala CH, Dusci L, Marshall BJ. Source: Antimicrobial Agents and Chemotherapy. 2003 December; 47(12): 3780-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638482

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Nitric oxide in Helicobacter pylori-induced apoptosis and its significance in gastric carcinogenesis. Author(s): Xia HH, Wong BC. Source: Journal of Gastroenterology and Hepatology. 2003 November; 18(11): 1227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535977

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Nocturnal gastric acid breakthrough during the administration of rabeprazole and ranitidine in Helicobacter pylori-negative subjects: effects of different regimens. Author(s): Adachi K, Komazawa Y, Fujishiro H, Mihara T, Ono M, Yuki M, Kawamura A, Karim Rumi MA, Amano Y, Kinoshita Y. Source: Journal of Gastroenterology. 2003; 38(9): 830-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564627

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201

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Nodular gastritis in adults is caused by Helicobacter pylori infection. Author(s): Miyamoto M, Haruma K, Yoshihara M, Hiyama T, Sumioka M, Nishisaka T, Tanaka S, Chayama K. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 968-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772798

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Non-invasive techniques for the diagnosis of Helicobacter pylori infection. Author(s): Gatta L, Ricci C, Tampieri A, Vaira D. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 June; 9(6): 489-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848723

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Noninvasive tests to diagnose Helicobacter pylori infection. Author(s): Gatta L, Ricci C, Tampieri A. Source: Current Gastroenterology Reports. 2003 October; 5(5): 351-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959712

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Non-steroidal anti-inflammatory drug-induced gastroduodenal toxicity and Helicobacter pylori. Author(s): Wardi J, Shirin H. Source: Isr Med Assoc J. 2003 March; 5(3): 195-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725142

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Novel diagnostic method of testing for Helicobacter pylori infection using the rapid leukocyte strip test, Leukostix. Author(s): Matsuda M, Noda Y, Takemori Y. Source: Journal of Gastroenterology and Hepatology. 2003 October; 18(10): 1196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974908

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Nurse-led dyspepsia clinic using the urea breath test for Helicobacter pylori. Author(s): Fraser A, Williamson S, Lane M, Hollis B. Source: N Z Med J. 2003 June 20; 116(1176): U479. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835807

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Of blood and guts: association between Helicobacter pylori and the gastric microcirculation. Author(s): Kalia N, Bardhan KD. Source: Journal of Gastroenterology and Hepatology. 2003 September; 18(9): 1010-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911655

202

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One-day quadruple therapy compared with 7-day triple therapy for Helicobacter pylori infection. Author(s): Lara LF, Cisneros G, Gurney M, Van Ness M, Jarjoura D, Moauro B, Polen A, Rutecki G, Whittier F. Source: Archives of Internal Medicine. 2003 September 22; 163(17): 2079-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504122

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One-week low-dose triple therapy without anti-acid treatment has sufficient efficacy on Helicobacter pylori eradication and ulcer healing. Author(s): Hsu CC, Lu SN, Changchien CS. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1731-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571829

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One-week triple therapy with esomeprazole, clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection. Author(s): Veldhuyzen Van Zanten S, Machado S, Lee J. Source: Alimentary Pharmacology & Therapeutics. 2003 June 1; 17(11): 1381-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786632

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Oral cavity as a potential source of gastric reinfection by Helicobacter pylori. Author(s): Karczewska E, Konturek JE, Konturek PC, Czesnikiewicz M, Sito E, Bielanski W, Kwiecien N, Obtulowicz W, Ziemniak W, Majka J, Hahn EG, Konturek SJ. Source: Digestive Diseases and Sciences. 2002 May; 47(5): 978-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12018924

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Oral Helicobacter pylori: can we stomach it? Author(s): Dowsett SA, Kowolik MJ. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 2003; 14(3): 226-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799325

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Outcome of patients with inconsistent results from 13C-urea breath test and bacterial culture at the time of assessment of Helicobacter pylori eradication therapy in Japan. Author(s): Nagahara Y, Mizuno M, Maga T, Ishiki K, Okuno T, Yoshida T, Yokota K, Oguma K, Okada H, Tsuji T. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1700-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571821

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Outcomes of pediatric gastroesophageal reflux disease: in the first year of life, in childhood, and in adults.oh, and should we really leave Helicobacter pylori alone? Author(s): Gold BD. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November-December; 37 Suppl 1: S33-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685076

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Overview on chemotaxis and acid resistance in Helicobacter pylori. Author(s): Valenzuela M, Cerda O, Toledo H. Source: Biol Res. 2003; 36(3-4): 429-36. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631875

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Oxidative damage of the gastric mucosa in Helicobacter pylori positive chronic atrophic and nonatrophic gastritis, before and after eradication. Author(s): Iacopini F, Consolazio A, Bosco D, Marcheggiano A, Bella A, Pica R, Paoluzi OA, Crispino P, Rivera M, Mottolese M, Nardi F, Paoluzi P. Source: Helicobacter. 2003; 8(5): 503-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535997

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Pathogenesis of Helicobacter pylori infection. Author(s): Lamarque D, M Peek R Jr. Source: Helicobacter. 2003; 8 Suppl 1: 21-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617214

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Persistent Helicobacter pylori infection and genetic polymorphisms of the host. Author(s): Hamajima N. Source: Nagoya J Med Sci. 2003 November; 66(3-4): 103-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727687

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Persistent infection with Helicobacter pylori and the development of gastric cancer. Author(s): Normark S, Nilsson C, Normark BH, Hornef MW. Source: Adv Cancer Res. 2003; 90: 63-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710947

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Pharmacoeconomics--determination of the cost-effectiveness of Helicobacter pylori eradication. Author(s): Curtiss FR. Source: J Manag Care Pharm. 2003 September-October; 9(5): 451-2, 455-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613444

204

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Potential role of Helicobacter pylori in hepatocarcinogenesis. Author(s): Ito K, Nakamura M, Toda G, Negishi M, Torii A, Ohno T. Source: International Journal of Molecular Medicine. 2004 February; 13(2): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719127

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Predictors of vitamin B12 deficiency: age and Helicobacter pylori load of antral mucosa. Author(s): Gumurdulu Y, Serin E, Ozer B, Kayaselcuk F, Kul K, Pata C, Guclu M, Gur G, Boyacioglu S. Source: Turk J Gastroenterol. 2003 March; 14(1): 44-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14593537

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Pregnant women and the Helicobacter pylori generation effect. Author(s): Eslick GD. Source: Helicobacter. 2003 December; 8(6): 643. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632679

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Prevalence of cagA and vacA genes in isolates from patients with Helicobacter pyloriassociated gastroduodenal diseases in Recife, Pernambuco, Brazil. Author(s): Brito CA, Silva LM, Juca N, Leal NC, de Souza W, Queiroz D, Cordeiro F, Silva NL. Source: Memorias Do Instituto Oswaldo Cruz. 2003 September; 98(6): 817-21. Epub 2003 October 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595461

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Prevalence of Helicobacter pylori infection among low socio-economic workers. Author(s): Bener A, Uduman SA, Ameen A, Alwash R, Pasha MA, Usmani MA, AI-Naili SR, Amiri KM. Source: J Commun Dis. 2002 September; 34(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703052

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Prevalence of Helicobacter pylori infection in Warao lineage communities of Delta Amacuro State, Venezuela. Author(s): Ortiz D, Cavazza ME, Rodriguez O, Hagel I, Correnti M, Convit J. Source: Memorias Do Instituto Oswaldo Cruz. 2003 September; 98(6): 721-5. Epub 2003 October 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595445

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205

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Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori. Author(s): Chi CH, Lin CY, Sheu BS, Yang HB, Huang AH, Wu JJ. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895220

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Quadruple therapy for initial eradication of Helicobacter pylori in peptic ulcer: comparison with triple therapy. Author(s): Pai CG, Thomas CP, Biswas A, Rao S, Ramnarayan K. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 85-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839378

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Quadruple treatments for Helicobacter pylori. Author(s): Mascitelli L, Pezzetta F. Source: Lancet. 2003 January 4; 361(9351): 86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517510

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Quantification of Helicobacter pylori resistance in functional and organic dyspepsia. Author(s): Rosandic M, Pilas V, Bevanda M, Falisevac V, Korac B. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 October; 27(5): 353-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383136

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Quantitative assessment of gastric juice urease activity in children infected with Helicobacter pylori. Author(s): Nijevitch AA, Shcherbakov PL. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1845-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135053

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Quantitative correlation of Helicobacter pylori stool antigen (HpSA) test with 13Curea breath test (13C-UBT) by the updated Sydney grading system of gastritis. Author(s): Chang MC, Chang YT, Sun CT, Wu MS, Wang HP, Lin JT. Source: Hepatogastroenterology. 2002 March-April; 49(44): 576-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11995501

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Quantitative determinations of duodenogastric reflux, prevalence of Helicobacter pylori infection, and concentrations of interleukin-8. Author(s): Fukuhara K, Osugi H, Takada N, Takemura M, Ohmoto Y, Kinoshita H. Source: World Journal of Surgery. 2003 May; 27(5): 567-70. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715225

206

Helicobacter pylori

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Randomized study of different 'second-line' therapies for Helicobacter pylori infection after failure of the standard 'Maastricht triple therapy'. Author(s): Perri F, Festa V, Merla A, Barberani F, Pilotto A, Andriulli A. Source: Alimentary Pharmacology & Therapeutics. 2003 October 15; 18(8): 815-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535875

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Rates of dyspepsia one year after Helicobacter pylori screening and eradication in a Danish population. Author(s): Wildner-Christensen M, Moller Hansen J, Schaffalitzky De Muckadell OB. Source: Gastroenterology. 2003 August; 125(2): 372-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891538

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Recent advances in Helicobacter pylori infection in children: from the petri dish to the playground. Author(s): Zheng PY, Jones NL. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 July; 17(7): 448-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915920

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Reduced incidence of acute graft versus host disease (GVHD) of the gut in Chinese carriers of Helicobacter pylori during allogeneic bone marrow transplantation. Author(s): Au WY, Wong RW, Wong BC, Lie AK, Liang R, Leung AY, Kwong YL. Source: Annals of Hematology. 2004 January; 83(1): 34-7. Epub 2003 October 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551739

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Refractory iron deficiency anemia--is Helicobacter pylori the culprit? Author(s): Pavithran K, Arjun R, Aruna R, Thomas M. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2003 April 28; 5(2): 34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603133

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Relation of serum ascorbic acid to Helicobacter pylori serology in US adults: the Third National Health and Nutrition Examination Survey. Author(s): Simon JA, Hudes ES, Perez-Perez GI. Source: Journal of the American College of Nutrition. 2003 August; 22(4): 283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897042

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Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample. Author(s): Redeen S, Petersson F, Jonsson KA, Borch K. Source: Endoscopy. 2003 November; 35(11): 946-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606018

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207

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Risk factors for Helicobacter pylori infection among a rural population in Japan: relation to living environment and medical history. Author(s): Nishise Y, Fukao A, Takahashi T. Source: J Epidemiol. 2003 September; 13(5): 266-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604222

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Role of antibiotic sensitivity testing before first-line Helicobacter pylori eradication treatments. Author(s): Neri M, Milano A, Laterza F, Di Bonaventura G, Piccolomini R, Caldarella MP, Balatsinou C, Lapenna D, Cuccurullo F. Source: Alimentary Pharmacology & Therapeutics. 2003 October 15; 18(8): 821-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535876

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Rosacea: a cutaneous marker of Helicobacter pylori infection? Results of a pilot study. Author(s): Diaz C, O'Callaghan CJ, Khan A, Ilchyshyn A. Source: Acta Dermato-Venereologica. 2003; 83(4): 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926800

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Serologic assay of Helicobacter pylori infection. Is it useful in hyperemesis gravidarum? Author(s): Berker B, Soylemez F, Cengiz SD, Kose SK. Source: J Reprod Med. 2003 October; 48(10): 809-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619649

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Seropositivity of Chlamydia pneumoniae and Helicobacter pylori among coronary heart disease patients and normal individuals in a South Indian population. Author(s): Chaudhury A, Rajasekhar D, Latheef SA, Subramanyam G. Source: Indian Heart J. 2003 July-August; 55(4): 384. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686675

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Simultaneous EBV-positive lymphoepithelioma-like carcinoma and EBV-negative intestinal-type adenocarcinoma in a patient with Helicobacter pylori-associated chronic gastritis. Author(s): Torlakovic G, Snover DC, Torlakovic E. Source: American Journal of Clinical Pathology. 2004 February; 121(2): 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983938

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Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori. Author(s): Tankovic J, Lascols C, Sculo Q, Petit JC, Soussy CJ. Source: Antimicrobial Agents and Chemotherapy. 2003 December; 47(12): 3942-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638505

208

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Sphingomyelinase of Helicobacter pylori-induced cytotoxicity in AGS gastric epithelial cells via activation of JNK kinase. Author(s): Tseng HJ, Chan CC, Chan EC. Source: Biochemical and Biophysical Research Communications. 2004 February 6; 314(2): 513-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733936

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Superoxide-dismutase activity of the gastric mucosa in patients with Helicobacter pylori infection. Author(s): Farkas R, Selmeci L, Tulassay Z, Pronai L. Source: Anticancer Res. 2003 September-October; 23(5B): 4309-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666643

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Susceptibilities to different antibiotics of Helicobacter pylori strains isolated from patients at the pediatric medical center of Tehran, Iran. Author(s): Falsafi T, Mobasheri F, Nariman F, Najafi M. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 387-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715786

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Susceptibility of Helicobacter pylori to metronidazole. Author(s): Perna F, Gatta L, Figura N, Ricci C, Tampieri A, Holton J, Miglioli M, Vaira D. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2157-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572561

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Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori. Author(s): Sarnelli G, Cuomo R, Janssens J, Tack J. Source: Digestive Diseases and Sciences. 2003 December; 48(12): 2229-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714606

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Systemic Tropheryma whippleii infection associated with monoclonal B-cell proliferation: a Helicobacter pylori-type pathogenesis? Author(s): Wang S, Ernst LM, Smith BR, Tallini G, Howe JG, Crouch J, Cooper DL. Source: Archives of Pathology & Laboratory Medicine. 2003 December; 127(12): 1619-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632565

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The clinical utility of string-PCR test in diagnosing Helicobacter pylori infection. Author(s): Wang SW, Yu FJ, Lo YC, Yang YC, Wu MT, Wu IC, Lee YC, Jan CM, Wang WM, Wu DC. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1208-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571700

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The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. Author(s): Zhou W, Yamazaki S, Yamakawa A, Ohtani M, Ito Y, Keida Y, Higashi H, Hatakeyama M, Si J, Azuma T. Source: Fems Immunology and Medical Microbiology. 2004 January 15; 40(1): 81-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734191

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The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. Author(s): Boncristiano M, Paccani SR, Barone S, Ulivieri C, Patrussi L, Ilver D, Amedei A, D'Elios MM, Telford JL, Baldari CT. Source: The Journal of Experimental Medicine. 2003 December 15; 198(12): 1887-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676300

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The seroprevalence of Helicobacter pylori in a referral population of children in the United States. Author(s): Chong SK, Lou Q, Zollinger TW, Rabinowitz S, Jibaly R, Tolia V, Elitsur Y, Gold BD, Rosenberg A, Johnson A, Elkayam O, Rosenthal P, Gilger M, Li BU, Peacock JS. Source: The American Journal of Gastroenterology. 2003 October; 98(10): 2162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572562

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The size of cagA based on repeat sequence has the responsibility of the location of Helicobacter pylori in the gastric mucus and the degree of gastric mucosal inflammation. Author(s): Karita M, Matsumoto S, Kamei T. Source: Microbiology and Immunology. 2003; 47(9): 619-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584609

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The test-and-treat strategy for Helicobacter pylori in uninvestigated dyspepsia. Author(s): Thibodeau LR. Source: Jaapa. 2003 August; 16(8): 20-2, 25-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968490

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Three-day intravenous triple therapy is not effective for the eradication of Helicobacter pylori infection in patients with bleeding gastro-duodenal ulcer. Author(s): Romero-Gomez M, Martinez-Delgado C, Hergueta P, Navarro JM, GarridoSerrano A, Santos O, Montojo C. Source: Alimentary Pharmacology & Therapeutics. 2003 November 15; 18(10): 1023-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616169

210

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Transmission of Helicobacter pylori infection in families of preschool-aged children from Minas Gerais, Brazil. Author(s): Rocha GA, Rocha AM, Silva LD, Santos A, Bocewicz AC, Queiroz Rd Rde M, Bethony J, Gazzinelli A, Correa-Oliveira R, Queiroz DM. Source: Tropical Medicine & International Health : Tm & Ih. 2003 November; 8(11): 98791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629764

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Treatment of Helicobacter pylori infection. Author(s): Perri F, Qasim A, Marras L, O'Morain C. Source: Helicobacter. 2003; 8 Suppl 1: 53-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617218

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Tremor, aphasia, and stuttering associated with Helicobacter pylori infection. Author(s): Tsao JW, Shad JA, Faillace WJ. Source: The American Journal of Medicine. 2004 February 1; 116(3): 211-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749173

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Ultrastructural morphology of Helicobacter pylori in post vagotomy dyspepsia. Author(s): Ghosh TK, Ghoshal UC, Chakraborty S. Source: Indian J Pathol Microbiol. 2002 January; 45(1): 83-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593571

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Unexpected decrease with age of Helicobacter pylori seroprevalence among Swedish blood donors. Author(s): Sorberg M, Nyren O, Granstrom M. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4038-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958222

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Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by Helicobacter pylori infection. Author(s): Nagasako T, Sugiyama T, Mizushima T, Miura Y, Kato M, Asaka M. Source: The Journal of Biological Chemistry. 2003 February 14; 278(7): 4821-5. Epub 2002 December 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473652

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UreC PCR based diagnosis of Helicobacter pylori infection and detection of cag A gene in gastric biopsies. Author(s): Mishra KK, Srivastava S, Dwivedi PP, Prasad KN, Ayyagari A. Source: Indian J Pathol Microbiol. 2002 January; 45(1): 31-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593561

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211

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Urinary 8-hydroxydeoxyguanosine excretion in children before and after therapy for eradication of Helicobacter pylori infection. Author(s): Shimizu T, Lee T, Shoji H, Kudo T, Satoh Y, Yamashiro Y. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 September; 92(9): 1026-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599063

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Urinary antibody titers to Helicobacter pylori and an impact of clinical characteristics. Author(s): Yamamoto T, Tamura M, Ishii T, Anjiki H, Hattori K, Saitoh M, Sanaka M, Kuyama Y. Source: Journal of Clinical Gastroenterology. 2003 April; 36(4): 329-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642740

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Use of bovine lactoferrin for Helicobacter pylori eradication. Author(s): Di Mario F, Aragona G, Dal Bo N, Cavestro GM, Cavallaro L, Iori V, Comparato G, Leandro G, Pilotto A, Franze A. Source: Dig Liver Dis. 2003 October; 35(10): 706-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620619

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Use of lactoferrin for Helicobacter pylori eradication. Author(s): Meyer JM. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702976

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Use of lactoferrin for Helicobacter pylori eradication. Preliminary results. Author(s): Di Mario F, Aragona G, Bo ND, Ingegnoli A, Cavestro GM, Moussa AM, Iori V, Leandro G, Pilotto A, Franze A. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 396-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702979

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Utility and limitations of a method for detecting Helicobacter pylori-specific antigens in the stool. Author(s): Matsuda M, Noda Y, Takemori Y. Source: Journal of Gastroenterology. 2003; 38(3): 222-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673444

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Validation of 13C-urea breathtest for the diagnosis of Helicobacter pylori infection in the Singapore population. Author(s): Chua TS, Fock KM, Teo EK, Ng TM. Source: Singapore Med J. 2002 August; 43(8): 408-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507026

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Validation of endoscopic 13C-urea breath test with nondispersive infrared spectrometric analysis in the management of Helicobacter pylori infection. Author(s): Isomoto H, Inoue K, Mizuta Y, Nakazato M, Kanazawa Y, Nishiyama H, Ohara H, Urata M, Omagari K, Miyazaki M, Murase K, Murata I, Kohno S. Source: Hepatogastroenterology. 2003 March-April; 50(50): 422-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749238

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Validation of the 13c-urea breath test for the initial diagnosis of helicobacter pylori infection and to confirm eradication after treatment. Author(s): Gisbert JP, Ducons J, Gomollon F, Dominguez-Munoz JE, Borda F, Mino G, Jimenez I, Vazquez MA, Santolaria S, Gallego S, Iglesias J, Pastor G, Hervas A, Pajares JM. Source: Rev Esp Enferm Dig. 2003 February; 95(2): 121-6, 115-20. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760719

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Value of PCR technique in detection of Helicobacter pylori in paraffin-embedded material. Author(s): Ciesielska U, Jagoda E, Marciniak Z. Source: Folia Histochem Cytobiol. 2002; 40(2): 129-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12056609

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Views on esomeprazole-based triple therapy to treat duodenal ulcer disease and Helicobacter pylori infection. Author(s): Singh-Ranger G. Source: European Journal of Gastroenterology & Hepatology. 2002 June; 14(6): 703; Author Reply 703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072608

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Virulence genes and neutral DNA markers of Helicobacter pylori isolates from different ethnic communities of West Bengal, India. Author(s): Datta S, Chattopadhyay S, Balakrish Nair G, Mukhopadhyay AK, Hembram J, Berg DE, Rani Saha D, Khan A, Santra A, Bhattacharya SK, Chowdhury A. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3737-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904384

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Virulence genes in Helicobacter pylori strains from West Bengal residents with overt H. pylori-associated disease and healthy volunteers. Author(s): Chattopadhyay S, Datta S, Chowdhury A, Chowdhury S, Mukhopadhyay AK, Rajendran K, Bhattacharya SK, Berg DE, Nair GB. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2622-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089290

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Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma? Author(s): Bravo LE, van Doom LJ, Realpe JL, Correa P. Source: The American Journal of Gastroenterology. 2002 November; 97(11): 2839-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425557

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Virus-cell fusion inhibitory activity of novel analogue peptides based on the HP (220) derived from N-terminus of Helicobacter pylori Ribosomal Protein L1. Author(s): Woo ER, Lee DG, Chang YS, Park Y, Hahm KS. Source: Protein and Peptide Letters. 2002 December; 9(6): 477-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553855

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Vitamin C and E supplements to lansoprazole-amoxicillin-metronidazole triple therapy may reduce the eradication rate of metronidazole-susceptible Helicobacter pylori infection. Author(s): Chuang CH, Sheu BS, Huang AH, Yang HB, Wu JJ. Source: Helicobacter. 2002 October; 7(5): 310-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390211

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What is the most effective regimen for eradication of Helicobacter pylori in patients who have failed a first eradication attempt? Author(s): Markova T, Schwartz K. Source: The Journal of Family Practice. 2002 January; 51(1): 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927054

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What is the role of serology in assessing Helicobacter pylori eradication? Author(s): Bergey B, Marchildon P, Peacock J, Megraud F. Source: Alimentary Pharmacology & Therapeutics. 2003 September 15; 18(6): 635-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969090

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What regimens eradicate Helicobacter pylori? Author(s): Malaty W, Stigleman S. Source: The Journal of Family Practice. 2003 October; 52(10): 799-803; Discussion 803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529606

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CHAPTER 2. NUTRITION AND HELICOBACTER PYLORI Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Helicobacter pylori.

Finding Nutrition Studies on Helicobacter Pylori 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 “Helicobacter pylori” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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The following is a typical result when searching for recently indexed consumer information on Helicobacter pylori: •

Does vitamin C intake slow the progression of gastric cancer in Helicobacter pyloriinfected populations? Author(s): Department of Gastroenterology, Loyola University of Chicago, Maywood, IL 60153, USA. Source: Feiz, Hamid Reza Mobarhan, Sohrab Nutr-Revolume 2002 January; 60(1): 34-6 0029-6643

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

A 3-day anti-Helicobacter pylori therapy is a good alternative for bleeding peptic ulcer patients with Helicobacter pylori infection. Author(s): Division of Gastroenterology, Department of Medicine, VGH-Taipei, Shih-Pai Rd, Sec 2, Taipei, Taiwan, 11217, ROC. Source: Hsieh, Y H Lin, H J Tseng, G Y Perng, C L Chang, F Y Lee, S D Hepatogastroenterology. 2001 Jul-August; 48(40): 1078-81 0172-6390

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A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori. Author(s): Public Health Laboratory, Gloucestershire Royal Hospital, Gloucester, UK. Source: McNulty, C A Wilson, M P Havinga, W Johnston, B O'Gara, E A Maslin, D J Helicobacter. 2001 September; 6(3): 249-53 1083-4389

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Alcohol consumption and Helicobacter pylori infection: results from the German National Health and Nutrition Survey. Author(s): Department of Epidemiology, University of Ulm, Germany. Source: Brenner, H Berg, G Lappus, N Kliebsch, U Bode, G Boeing, H Epidemiology. 1999 May; 10(3): 214-8 1044-3983

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Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium Helicobacter pylori. Source: Wang, H.H. Chung, J.G. Ho, C.C. Wu, L.T. Chang, S.H. Planta-med. Stuttgart : Georg Thieme Verlag,. March 1998. volume 64 (2) page 176-178. 0032-0943

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Alternative and rescue treatment regimens for Helicobacter pylori eradication. Author(s): Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, China. [email protected] Source: Xia, H H Yu Wong, B C Talley, N J Lam, S K Expert-Opin-Pharmacother. 2002 September; 3(9): 1301-11 1465-6566

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Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection. Author(s): Department of Internal Medicine, Gastroenterology Unit, Casa Sollievo della Sofferenza Hospital, I.R.C.C.S., San Giovanni Rotondo, Italy. Source: Perri, Francesco Festa, Virginia Merla, Antonio Quitadamo, Michele Clemente, Rocco Andriulli, Angelo Helicobacter. 2002 April; 7(2): 99-104 1083-4389

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Amoxycillin, clarithromycin and either sucralfate or pantoprazole for eradication of Helicobacter pylori in duodenal ulcer (a randomized controlled trial). Author(s): Internal Clinic, Clinical Hospital Osijek. [email protected]

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Source: Vcev, A Vceva, A Kurbel, S Takac, B Stimac, D Ivandic, A Ostojic, R Barbir, A Hovat, D Mihaljevic, S Wien-Klin-Wochenschr. 2001 December 17; 113(23-24): 939-41 0043-5325 •

Antibacterial activity of black myrobalan (Terminalia chebula Retz) against Helicobacter pylori. Author(s): Department of Microbiology and Biological Sciences, University of Tehran, Tehran, Iran. Source: Malekzadeh, F Ehsanifar, H Shahamat, M Levin, M Colwell, R R Int-JAntimicrob-Agents. 2001 July; 18(1): 85-8 0924-8579

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Anti-Helicobacter pylori activity of quinolone alkaloids from Evodiae fructus. Author(s): Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon. Source: Rho, T C Bae, E A Kim, D H Oh, W K Kim, B Y Ahn, J S Lee, H S Biol-PharmBull. 1999 October; 22(10): 1141-3 0918-6158

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Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori. Author(s): Laboratorio di Batteriologia e Micologia--Area Infettivologica, IRCCS S. Matteo, Pavia, Italy. [email protected] Source: Marone, P Bono, L Leone, E Bona, S Carretto, E Perversi, L J-Chemother. 2001 December; 13(6): 611-4 1120-009X

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Bactericidal effects of fatty acids and monoglycerides on Helicobacter pylori. Author(s): Institute of Biology, University of Iceland, Grensasvegur 12, 108, Reykjavik, Iceland. [email protected] Source: Bergsson, G Steingrimsson, O ThorMarch, H Int-J-Antimicrob-Agents. 2002 October; 20(4): 258-62 0924-8579

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Caspase-3 activity and expression of Bcl-2 family in human neutrophils by Helicobacter pylori water-soluble proteins. Author(s): Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. Source: Kim, J S Kim, J M Jung, H C Song, I S Helicobacter. 2001 September; 6(3): 207-15 1083-4389

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Cloning and expression of Helicobacter pylori GDP-l-fucose synthesizing enzymes (GMD and GMER) in Saccharomyces cerevisiae. Author(s): Department of Bacteriology and Immunology, Haartman Institute and Biomedicum, University of Helsinki, Finland. Source: Jarvinen, N Maki, M Rabina, J Roos, C Mattila, P Renkonen, R Eur-J-Biochem. 2001 December; 268(24): 6458-64 0014-2956

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Composition of the Essential Oil of Two Nepeta Species and in vitro Evaluation of their Activity against Helicobacter pylori. Author(s): Division of Pharmacognosy, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens, Greece. Source: Kalpoutzakis, E Aligiannis, N Mentis, A Mitaku, S Charvala, C Planta-Med. 2001 December; 67(9): 880-3 0032-0943

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Consequences of Helicobacter pylori infection on the absorption of micronutrients. Author(s): Department of Digestive and Liver Disease, II Medical School, Sant'Andrea Hospital, University La Sapienza Rome, Italy. [email protected] Source: Annibale, B Capurso, G Delle Fave, G Dig-Liver-Dis. 2002 September; 34 Suppl 2: S72-7 1590-8658

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Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users. Author(s): Department of Medicine, Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX 77030, USA. Source: Graham, David Y Helicobacter. 2002 February; 7(1): 1-8 1083-4389

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Dental implications of Helicobacter pylori. Author(s): Department of Oral Medicine and Oral Pathology, Faculty of Dentistry, University of Toronto, Toronto, Ontario. Source: Kilmartin, C M J-Can-Dent-Assoc. 2002 September; 68(8): 489-93 1488-2159

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Diagnostic methods for detecting forms and strains of Helicobacter pylori and evaluation of its eradication. Author(s): Central Institute of Gastroenterology, Moscow. Source: LogiNovember, A S Reshetnyak, V I Dudik, T V Vostroknutova, G N Il'chenko, A A Kaprel'yants, A S Bull-Exp-Biol-Med. 2001 August; 132(2): 802-6 0007-4888

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Dietary factors influence the recovery rates of Helicobacter pylori in a BALB/cA mouse model. Author(s): Department of Infectious Diseases and Medical Microbiology, Lund University, Sweden. Source: Wang, X Sjunnesson, H Sturegard, E Wadstrom, T Willen, R Aleljung, P Zentralbl-Bakteriol. 1998 October; 288(2): 195-205 0934-8840

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Disease-specific Helicobacter pylori virulence factors: the unfulfilled promise. Author(s): Department of Medicine, VA Medical Center, and Baylor College of Medicine, Houston, Texas, USA. Source: Graham, D Y Yamaoka, Y Helicobacter. 2000; 5 Suppl 1S3-9; discussion S27-31 1083-4389

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Effect of antioxidants on the immune response of Helicobacter pylori. Author(s): Hacettepe University, School of Medicine, Department of Microbiology and Clinical Microbiology, Ankara, Turkey. [email protected] Source: Akyon, Y Clin-Microbiol-Infect. 2002 July; 8(7): 438-41 1198-743X

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Effect of Helicobacter pylori eradication on peptic ulcer disease complicated with outlet obstruction. Author(s): Departments of Gastroenterology, Pathology, and Surgery, Inonu University School of Medicine, Malatya, Turkey. Source: Taskin, V Gurer, I Ozyilkan, E Sare, M Hilmioglu, F Helicobacter. 2000 March; 5(1): 38-40 1083-4389

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Effectiveness of ranitidine bismuth citrate based triple therapy for treating Helicobacter pylori. Author(s): Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. Source: Thong Ngam, D Tangkijvanich, P Treeprasertsuk, S Wisedopas, N Kullavanijaya, P J-Med-Assoc-Thai. 2002 October; 85(10): 1054-9 0125-2208

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Effects of interleukin-8 and Helicobacter pylori on histamine release from isolated canine gastric mucosal mast cells. Author(s): Third Department of Internal Medicine, Teikyo University Ichihara Hospital, Anesaki, Ichihara, Japan. Source: Yakabi, Koji Arimura, Takashi Koyanagi, Mitsuhito Uehigashi, Yoichi Ro, Shoki Minagawa, Yasutaka Nakamura, Takashi J-Gastroenterol. 2002 January; 37(1): 10-6 09441174

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Effects of three different fish oil formulations on Helicobacter pylori growth and viability: in vitro study. Author(s): L. Sacco Teaching Hospital, University of Milan, Milano, Italy. [email protected] Source: Drago, L Mombelli, B Ciardo, G De Vecchi, E Gismondo, M R J-Chemother. 1999 June; 11(3): 207-10 1120-009X

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Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate. Author(s): Division of Gastroenterology, Department of Medicine, Medical School of Ribeirao Preto, Brazil. [email protected] Source: Meneghelli, U G Boaventura, S Moraes Filho, J P Leitao, O Ferrari, A P Almeida, J R Magalhaes, A F Castro, L P Haddad, M T Tolentino, M Jorge, J L Silva, E Maguilnik, I Fischer, R Dis-Esophagus. 2002; 15(1): 50-6 1120-8694

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Efficacy of Helicobacter pylori eradication therapies: a single centre observational study. Author(s): Medical School, University of East Anglia, Norwich NR74 7TJ, United Kindgom. [email protected] Source: Beales, I L BMC-Gastroenterol. 2001; 1(1): 7 1471-230X

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Epidemiological study on food intake and Helicobacter pylori infection. Author(s): Department of Medicine, Kurume University School of Medicine, Japan. Source: Toyonaga, A Okamatsu, H Sasaki, K Kimura, H Saito, T Shimizu, S Fukuizumi, K Tsuruta, O Tanikawa, K Sata, M Kurume-Med-J. 2000; 47(1): 25-30 0023-5679

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Epidemiology of Helicobacter pylori and gastric cancer. Author(s): Department of Public Health, Aichi Medical University School of Medicine, 21 Karimata, Yazako, Nagakute-cho, Aichi 480-1195, Japan. Source: Kikuchi, S Gastric-Cancer. 2002; 5(1): 6-15 1436-3291

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Eradication of Helicobacter pylori in duodenal ulcer disease tetracycline & furazolidone vs. metronidazole & amoxicillin in omeprazole based triple therapy. Author(s): Gastrointestinal & liver Diseases Research center, Guilan University of Medical Sciences, Rasht, Iran. [email protected] Source: Mansour Ghanaei, Fariborz Fallah, Mohammad S Shafaghi, Afshin Med-SciMonit. 2002 March; 8(3): PI27-30 1234-1010

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Evaluation of the factors influencing stomach-specific delivery of antibacterial agents for Helicobacter pylori infection. Author(s): School of Pharmacy, Northeastern University, Boston, MA 02115, USA. Source: Shah, S Qaqish, R Patel, V Amiji, M J-Pharm-Pharmacol. 1999 June; 51(6): 667-72 0022-3573

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Factors affecting the validity of the 13C-urea breath test for in vivo determination of Helicobacter pylori infection status in a mouse model. Author(s): Child Health Research Institute, Women's and Children's Hospital, North Adelaide, Australia. Source: Hammond, P D Stutzenberger, F J Butler, R N Read, L C Davidson, G P Helicobacter. 1999 December; 4(4): 260-5 1083-4389

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Helicobacter pylori eradication in patients on long-term H2 receptor antagonists. Economic and symptomatic benefits. A large prospective study in primary care. Author(s): Department of Gastroenterology, Hull Royal Infirmary, Anlaby Road, UK. Source: Verma, Sumita Giaffer, Mustafa H Helicobacter. 2002 April; 7(2): 91-8 1083-4389

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Hemolytic properties and riboflavin synthesis of Helicobacter pylori: cloning and functional characterization of the ribA gene encoding GTP-cyclohydrolase II that confers hemolytic activity to Escherichia coli. Author(s): Institute of Medical Microbiology, Department of Microbiology and Hygiene, Freiburg, Germany. [email protected] Source: Bereswill, S Fassbinder, F Volzing, C Covacci, A Haas, R Kist, M Med-MicrobiolImmunol-(Berl). 1998 March; 186(4): 177-87 0300-8584

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High intake of selenium, beta-carotene, and vitamins A, C, and E reduces growth of Helicobacter pylori in the guinea pig. Author(s): Department of Medical Microbiology, Dermatology and Infection, Lund University, Sweden. Source: Sjunnesson, H Sturegard, E Willen, R Wadstrom, T Comp-Med. 2001 October; 51(5): 418-23

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How does H. pylori infection cause gastric cancer? Author(s): University Department of Medicine & Therapeutics, Western Infirmary, Glasgow, Scotland, UK. [email protected] Source: McColl, K E El OMarch, E Keio-J-Med. 2002 December; 51 Suppl 2: 53-6 00229717

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Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures. Author(s): Department of Gastroenterology/Hepatology, University Hospital, Magdeburg, Germany. Source: Treiber, G Ammon, S Malfertheiner, P Klotz, U Helicobacter. 2002 August; 7(4): 225-31 1083-4389

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Impact of Helicobacter pylori on the development of vitamin B12 deficiency in the absence of gastric atrophy. Author(s): Department of Gastroenterology, Baskent University Faculty of Medicine, Adana Teaching and Medical Research Center, Adana, Turkey. Source: Serin, E Gumurdulu, Y Ozer, B Kayaselcuk, F Yilmaz, U Kocak, R Helicobacter. 2002 December; 7(6): 337-41 1083-4389

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In vitro anti-helicobacter pylori activity of irisolidone isolated from the flowers and rhizomes of Pueraria thunbergiana. Source: Bae, E.A. Han, M.J. Kim, D.H. Planta-med. Stuttgart : Georg Thieme Verlag,. March 2001. volume 67 (2) page 161-163. 0032-0943

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Inhibition of Helicobacter pylori hemagglutination by polysaccharide fractions from roots of Panax ginseng. Author(s): Graduate School of Biotechnology, Korea University, Seoul, Korea. Source: Belogortseva, N I Yoon, J Y Kim, K H Planta-Med. 2000 April; 66(3): 217-20 00320943

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Inhibitory actions of ellagic acid on growth and arylamine N-acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients. Author(s): Department of Medicine, China Medical College, Taiwan, Republic of China. Source: Chung, J G Microbios. 1998; 93(375): 115-27 0026-2633

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Inhibitory effect of sofalcone on tumor necrosis factor-alpha and interleukin-1 beta production in human monocytes stimulated by Helicobacter pylori water extract. Author(s): Department of Gastroenterology, Osaka City University Medical School, 1-43 Asahimachi, Abenoku Osaka 545-8585, Japan. [email protected]

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Source: Fujiwara, Y Higuchi, K Fukuda, T Watanabe, T Tominaga, K Arakawa, T DrugsExp-Clin-Res. 2001; 27(3): 103-6 0378-6501 •

Invasiveness of Helicobacter pylori into human gastric mucosa. Author(s): Department of Pathology, Gyeongsang National University College of Medicine, Chinju, Korea. [email protected] Source: Ko, G H Kang, S M Kim, Y K Lee, J H Park, C K Youn, H S Baik, S C Cho, M J Lee, W K Rhee, K H Helicobacter. 1999 June; 4(2): 77-81 1083-4389

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Marked enhancement by fish meal of Helicobacter pylori-induced gastritis in Mongolian gerbils. Author(s): Cancer Prevention Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. Source: Tanigawa, T Kawamori, T Iimuro, M Ohta, T Higuchi, K Arakawa, T Sugimura, T Wakabayashi, K Jpn-J-Cancer-Res. 2000 August; 91(8): 769-73 0910-5050

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Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease. Author(s): Hospital das Clinicas, Faculty of Medicine, University of Sao Paulo, Brazil. Source: Silva, F M Eisig, J N Chehter, E Z Silva, J J Laudanna, A A Rev-Hosp-Clin-FacMed-Sao-Paulo. 2002 Sep-October; 57(5): 205-8 0041-8781

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Pathological issues of gastric and lower esophageal cancer: helicobacter pylori infection and its eradication. Author(s): Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan. Source: Fujimori, T Kawamata, H Ichikawa, K Ono, Y Okura, Y Tomita, S Imura, J JGastroenterol. 2002; 37 Suppl 13: 28-33 0944-1174

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Patients with dyspepsia benefit from eradication of Helicobacter pylori if other organic causes for dyspepsia were carefully ruled out. Author(s): Department of Gastroenterology, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany. Source: Bojarski, C Epple, H J Kirstein, F W Fromm, M Bisson, S Riecken, E O Schulzke, J D Z-Gastroenterol. 2000 March; 38(3): 211-9 0044-2771

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Probiotics and Helicobacter pylori eradication. Author(s): Internal Medicine Department, Catholic University, Rome, Italy. Source: Canducci, F Cremonini, F Armuzzi, A Di Caro, S Gabrielli, M Santarelli, L Nista, E Lupascu, A De Martini, D Gasbarrini, A Dig-Liver-Dis. 2002 September; 34 Suppl 2: S81-3 1590-8658

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Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection. Author(s): Gastroenterology Department, Virgen Macarena University Hospital, Seville, Spain. [email protected] Source: Hergueta Delgado, P Rojas Feria, M Romero Castro, R Mendoza Olivares, F J Gomez Rodriguez, B Pellicer Bautista, F J Herrerias Gutierrez, J M Rev-Esp-Enferm-Dig. 2002 January; 94(1): 19-24 1130-0108

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Recurrent giant longitudinal duodenal ulcer with massive hemorrhage in a Helicobacter pylori-negative patient. Author(s): Department of Internal Medicine, Miyoshi Prefectural Hospital, Tokushima, Japan. Source: Fujimoto, M Shimizu, I Horie, T Inoue, H Okazaki, M Niki, M Shiraishi, T Fujiwara, S Murata, M Yamamoto, K Iuchi, A Hino, A Ito, S J-Med-Invest. 2001 August; 48(3-4): 210-5 1343-1420

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Reduced L-dopa absorption and increased clinical fluctuations in Helicobacter pyloriinfected Parkinson's disease patients. Author(s): Neurological Clinic, University of Rome Tor Vergata, Italy. Source: Pierantozzi, M Pietroiusti, A Sancesario, G Lunardi, G Fedele, E Giacomini, P Frasca, S Galante, A Marciani, M G Stanzione, P Neurol-Sci. 2001 February; 22(1): 89-91 1590-1874

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Relationship between enterogastric reflux estimated by scintigraphy and the presence of Helicobacter pylori. Author(s): Institute for Nuclear Medicine, Clinical Centre of Serbia, Belgrade, Yugoslavia. [email protected] Source: Artiko, V M Chebib, H Y Ugljesic, M B Petrovic, M N Obradovic, V B Hepatogastroenterology. 1999 Mar-April; 46(26): 1234-7 0172-6390

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Resolution of Menetrier's disease after Helicobacter pylori eradication therapy. Author(s): Sir Charles Gairdner Hospital, Perth, Western Australia. Source: Hamlin, M Shepherd, K Kennedy, M N-Z-Med-J. 2001 August 24; 114(1138): 3823 0028-8446

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Role of ERK and p38 mitogen-activated protein kinase cascades in gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide. Author(s): Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA. [email protected] Source: Slomiany, B L Slomiany, A IUBMB-Life. 2001 May; 51(5): 315-20 1521-6543

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Sufficient effect of 1-week omeprazole and amoxicillin dual treatment for Helicobacter pylori eradication in cytochrome P450 2C19 poor metabolizers. Author(s): Second Department of Internal Medicine, Kobe University School of Medicine, Japan. Source: Aoyama, N Tanigawara, Y Kita, T Sakai, T Shirakawa, K Shirasaka, D Kodama, F Okumura, K Kasuga, M J-Gastroenterol. 1999; 34 Suppl 1180-3 0944-1174

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Susceptibility of Helicobacter pylori to mupirocin, oxazolidinones, quinupristin/dalfopristin and new quinolones. Author(s): Departamento de Microbiologia and Servicio de Medicina Interna, Hospital Universitario, Paseo de San Vicente 108, 37007 Salamanca, Spain. [email protected] Source: Sanchez, J E Saenz, N G Rincon, M R Martin, I T Sanchez, E G Martinez, M J JAntimicrob-Chemother. 2000 August; 46(2): 283-5 0305-7453

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Synergistic interaction between Helicobacter pylori gastritis and diet in gastric cancer. Author(s): Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Tokyo, Japan. [email protected] Source: Yamaguchi, N Kakizoe, T Lancet-Oncol. 2001 February; 2(2): 88-94 1470-2045

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The antioxidant effect of rebamipide on oxygen free radical production by H. pyloriactivated human neutrophils: in comparison with N-acetylcysteine, ascorbic acid and glutathione. Author(s): Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Korea. Source: Hong, W S Jung, H Y Yang, S K Myung, S J Kim, J H Min, Y I Chung, M H Lee, H S Kim, H W Pharmacol-Res. 2001 October; 44(4): 293-7 1043-6618

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The Helicobacter pylori fatty acid cis-9,10-methyleneoctadecanoic acid stimulates protein kinase C and increases DNA synthesis of gastric HM02 cells. Author(s): Department of General Pharmacology, Hannover Medical School, Germany.

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Source: Beil, W Obst, B Wagner, S Sewing, K F Br-J-Cancer. 1998 June; 77(11): 1852-6 0007-0920 •

The impact of primary antibiotic resistance on the efficacy of ranitidine bismuth citrate- vs. omeprazole-based one-week triple therapies in H. pylori eradication--a randomised controlled trial. Author(s): Department of Hepatogastroenterology, Internal Medicine, General Hospital Sveti Duh, Zagreb, Croatia. Source: Bago, J Halle, Z B Strinic, D Kucisec, N Jandric, D Bevanda, M Tomic, M Bilic, A Wien-Klin-Wochenschr. 2002 June 28; 114(12): 448-53 0043-5325

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Two new treatment regimens for Helicobacter pylori eradication: a randomised study. Author(s): Division of Gastroenterology and Digestive Endoscopy, Riuniti Hospital, Foggia, Italy. Source: De Francesco, V Zullo, A Hassan, C Faleo, D Ierardi, E Panella, C Morini, S DigLiver-Dis. 2001 November; 33(8): 676-9

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Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter pylori-infected human gastric epithelial cells: possible role of interferon-gamma in polarized nitric oxide secretion. Author(s): Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul 133-791, Korea. Source: Kim, Jung Mogg Kim, Joo Sung Jung, Hyun Chae Song, In Sung Kim, Chung Yong Helicobacter. 2002 April; 7(2): 116-28 1083-4389

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YM-181741, a novel benz[a]anthraquinone antibiotic with anti-Helicobacter pylori activity from Streptomyces sp. Author(s): Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan. [email protected] Source: Taniguchi, Masatoshi Nagai, Koji Watanabe, Masato Nimura, Nami Suzuki, Ken ichi Tanaka, Akihiro J-Antibiot-(Tokyo). 2002 January; 55(1): 30-5 0021-8820

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 Helicobacter pylori; 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 B12 Source: Healthnotes, Inc.; www.healthnotes.com

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Food and Diet Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. DISSERTATIONS ON HELICOBACTER PYLORI Overview In this chapter, we will give you a bibliography on recent dissertations relating to Helicobacter pylori. 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 “Helicobacter pylori” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Helicobacter pylori, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Helicobacter Pylori 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 Helicobacter pylori. 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 Virtual Study of the Role of Gastric Acid in Helicobacter Pylori Infection of a Human Host by Joseph, Ian Miguel Peterson; PhD from University of Michigan, 2003, 223 pages http://wwwlib.umi.com/dissertations/fullcit/3106094

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Conversion of Gdp-mannose into Various Gdp-deoxyhexoses in Gram-negative Bacteria (Actinobacillus Actinomycetemcomitans, Pseudomonas Aeruginosa, Helicobacter Pylori) by Maki, Minna; PhD from Helsingin Yliopisto (Finland), 2003, 63 pages http://wwwlib.umi.com/dissertations/fullcit/f59009

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Lipid Rafts Are Essential for Cellular Intoxication Mediated by Helicobacter Pylori Vacuolating Toxin by Patel, Hetal Kanubhai; PhD from University of Houston, 2003, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3085617

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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 4. PATENTS ON HELICOBACTER PYLORI Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Helicobacter pylori” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Helicobacter pylori, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Helicobacter Pylori By performing a patent search focusing on Helicobacter pylori, 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. 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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

Adherence gene from Helicobacter pylori and polypeptide coded thereby Inventor(s): Blum; Andre (Romammotier, CH), Corthesy-Theulaz; Irene (Lausanne, CH), Haas; Rainer (Tubingen, DE), Meyer; Thomas F. (Tubingen, DE), Odenbreit; Stefan (Ammerbuch, DE) Assignee(s): Max-planck-gesellschaft Zur Foderung Der Wissenscaften E.v. (munchen, De) Patent Number: 6,593,461 Date filed: December 10, 1997 Abstract: The present invention concerns an adherence gene from Helicobacter pylori, a polypeptide coded thereby and antibodies against the polypeptide. Excerpt(s): The present invention concerns a method for identifying secretory genes and in particular adherence genes from Helicobacter pylori. In addition the invention concerns a gene bank suitable for identifying secretory genes from H. pylori, polynucleotides and polypeptides a obtainable from this gene bank, in particular the alpA-gene from Helicobacter pylori and the polypeptide which it codes. These polynucleotides and polypeptides can be used to diagnose, prevent and treat a Helicobacter infection. The occurrence of spiral bacteria in the human gastric mucous membrane has been known for a long time (Bizzozero, 1893). The fact that these are pathogenic germs was, however, not realized until the successful isolation and culture of this bacterium by Marshall and Warren (Warren and Marshall, 1983; Marshall et al., 1984) from the gastric mucous membrane of a patient with a gastric ulcer (ulcus ventriculi). As the first analyses showed the isolated microorganisms were gramnegative, spiral bacteria with an extremely high motility and the unusual ability of being able to survive in a strongly acidic environment (up to ca. pH 1.5). The germs which were originally denoted Campylobacter pylori were finally classified on the basis of biochemical and morphological characteristics in the newly established genus "Helicobacter" (Goodwin et al., 1989). The importance of Helicobacter pylori infection and the implications of this discovery already became clear within a few years. Epidemiological investigations by Taylor and Blaser (1991) showed that the H. pylori infection occurs world-wide and that ca. 50% of the population are infected with this bacterium, the infection rate being higher in the developing countries than in industrialized countries. Furthermore it was observed that the probability of a chronic H. pylori infection increases drastically with increasing age. Hence the H. pylori infection is among the most frequent chronic bacterial infections of humans. Web site: http://www.delphion.com/details?pn=US06593461__

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Antibacterial compositions with synergistic effect, drugs and remedies for digestive diseases containing the same, process for the production thereof and preparations associated therewith Inventor(s): Fujii; Kenji (Akashi, JP), Hidaka; Takayoshi (Kobe, JP), Hosoe; Kazunori (Takasago, JP), Yamashita; Katsuji (Kobe, JP) Assignee(s): Kaneka Corporation (osaka, Jp) Patent Number: 6,362,169 Date filed: August 22, 2000 Abstract: Antibacterial compositions comprising (1) a rifamycin derivative represented by the formula (I) or its physiologically acceptable salt, and (2) a proton pump inhibitor (a) or a bismuth preparation (b) wherein the components (1) and (2) are used in such amounts as producing a synergistic effect against Helicobacter pylori, drugs and remedies for digestive organ diseases which contain the antibacterial compositions, process for producing them, and pharmaceutical preparations related to the antibacterial compositions. The compositions can be administered to patients with digestive diseases caused by infection of Helicobacter pylori in a smaller dose and at a lower administration frequency as compared with conventional remedies. Excerpt(s): The present invention relates to an antibacterial composition against Helicobacter pylori. More particularly, the invention relates to drugs containing the antibacterial composition, remedies for diseases of digestive organs, e.g., gastritis, gastroduodenitis, erosive gastritis, gastric erosion, erosive duodenitis, gastric ulcer and duodenal ulcer, caused by the infection with Helicobacter pylori which is bacteria difficult to be eradicated by usual antibacterial materials such as antibiotics and synthetic antibacterial agents, a process for preparing them, and pharmaceutical preparations related to the antibacterial composition. It is known that Helicobacter pylori is bacteria causing active chronic gastritis and is also greatly associated with gastric ulcer and duodenal ulcer. It is acknowledged that by eradication of infecting Helicobacter pylori, active chronic gastritis is cured and relapse of gastric ulcer and duodenal ulcer is remarkably decreased. For treatment to eradicate Helicobacter pylori, there have been used, for example, antibacterial agents such as amoxicillin, ampicillin, clarithromycin, ofloxacin and tetracycline, bismuth preparations such as colloidal bismuth subcitrate and bismuth subsalicylate, antiprotozoals such as tinidazole and metronidazole, proton pump inhibitors such as omeprazole and lansoprazole, or drugs for gastrointestinal ulcer which are H.sub.2 blocker such as cimetidine and ranitidine. At present, one or two are selected from the antibacterial agents, and one or two are selected from the bismuth preparations, the antiprotozoals and the drugs for gastrointestinal ulcer, and a combination of two or three agents selected from the respective groups is administered for the treatment. Web site: http://www.delphion.com/details?pn=US06362169__

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Antimicrobial activity of hops extract against Clostridium botulinum, Clostridium difficile and Helicobacter pylori Inventor(s): Haas; Gerhard J. (Woodcliff Lake, NJ), Johnson; Eric A. (Madison, WI) Assignee(s): S. S. Steiner, Inc. (new York, Ny) Patent Number: 6,251,461 Date filed: October 10, 1997

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Abstract: The present invention relates to the discovery that hop extract is useful as an antibacterial agent against the dangerous pathogens Clostridium botulinum, Clostridium difficile, and Helicobacter pylori at levels below that at which a flavor from the acids contained therein is objectionable. More specifically, a process and associated product is described herein, comprising applying a solution of hop extract to a food, beverage or other medium so that the final concentration of hop ingredients is about 1 ppm or higher in order to inhibit the growth of Clostridium botulinum, Clostridium difficile, and/or Helicobacter pylori. Excerpt(s): The present invention relates to the use of hop extracts for controlling Clostridium botulinum, Clostridium difficile, and Helicobacter pylori. The most prevalent groups of bitter acids found as components of hops are the alpha-acids and beta-acids, also referred to as humulones and lupulones, respectively. Both contribute bitterness to beer, but the alpha-acids are much more intense in this regard than the beta-acids. Producers of hop extracts have recently used liquid carbon dioxide under supercritical conditions. A by-product of the operation is a product which contains approximately 61 weight percent beta-acids, the remainder consisting essentially of other hop resins. Quite apart from their use in beer, hops and hop acids have also been recognized as microbial inhibitors. More specifically, hop acids and resins have been shown to be primarily active against some gram positive bacteria and Mycobacteria. Activity against gram negative bacteria is far less pronounced. It has been suggested that the reduced effect was due to induced permeability of the cell membrane in gram positive bacteria, but was inactivated by the serum phosphatides in gram negative bacteria. Arch. Mikrobiol. 94, pp. 159-171, 1973. Web site: http://www.delphion.com/details?pn=US06251461__ •

Blood group antigen binding protein and corresponding agents Inventor(s): Arnqvist; Anna (Ume.ang., SE), Boren; Thomas (Torelv.ang.gen 68, S-906 28 Ume.ang., SE), Ilver; Dag (Ume.ang., SE), Normark; Staffan (Stockholm, SE) Assignee(s): Boren; Thomas (umea, Se) Patent Number: 6,410,719 Date filed: February 10, 1998 Abstract: A novel bacterial blood group antigen binding (BAB) adhesin protein was isolated and purified, whereby said protein or fractions thereof bind specifically to Helicobacter pylori fucosylated blood group antibodies. The protein sequence of said adhesin is disclosed in this application. Simultaneously the DNA sequences for two genes, babA and babB, producing highly similar proteins, are disclosed. Said adhesin and/or DNA is useful for diagnose and therapy and/or profylax directed against H. pylori induced infections, e.g. gastritis and acid peptic disease. Excerpt(s): The present invention relates to materials and methods for prevention, treatment and diagnosing of infections caused by Helicobacter pylori. More specifically the present invention relates to polypeptides and antibodies useful in vaccines for the treatment and prevention of pathologic infections caused by Helicobacter pylori strains. The present invention specifically relates to a bacterial blood group antigen binding adhesin (BAB-adhesin). The present invention further relates to polynucleotides useful for the recombinant production of said polypeptides and for use in immunization therapies. In addition, it relates to polypeptides, antibodies, and polynucleotides used for the detection of said bacteria. Helicobacter pylori is a causative agent for acid peptic

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disease and the presence of this organism is highly correlated to the development of gastric adenocarcinoma. Bacterial adherence to the human gastric epithelial lining was recently shown to be mediated by fucosylated blood group antigens. The foregoing makes the prevention, diagnosing and treatment of H. pylori infections an urgent task. Further, the fact that developing countries frequently lack the resources for conventional treatment of gastric ulcers further underlines the importance of finding new ways of diagnosing, treatment and prevention of H. pylori induced infections. It is obvious, for many reasons, that disease prevention with vaccines is a preferable mode. A vaccine would provide an easily administered and economical prophylactic regimen against H. pylori infections. An effective vaccine against H. pylori is nevertheless presently lacking. Web site: http://www.delphion.com/details?pn=US06410719__ •

Cloning and characterization of FLBA gene of H. pylori production of aflagellate Inventor(s): Labigne; Agnes (Bures sur Yvette, FR), Suerbaum; Sebastian (Bochum, DE) Assignee(s): Institut National DE LA Sante ET DE LA Recherche Medicale (paris, Fr), Institut Pasteur (paris, Fr) Patent Number: 6,476,213 Date filed: June 28, 1996 Abstract: The present application relates to nucleotide sequences which regulate the biosynthesis of the flagella proteins Helicobacter pylori, to the proteins encoded by these sequences and to aflagellate bacterial strains. The invention also relates to the use of these means for detecting an infection due to H. pylori or for protecting against such an infection. Excerpt(s): Helicobacter pylori (also designated as H.pylori) is a Gram-negative bacterium which, to date, has been found exclusively on the surface of the mucosa of the stomach in man. In common with most bacteria, H.pylori is sensitive to a medium which is at acid pH but, nevertheless, is able to tolerate acidity in the presence of physiological concentrations of urea (Marshall et al. (1990) Gastroenterol. 99: 697-702). By hydrolysing the urea to form carbon dioxide and ammonia, which are released into the microenvironment of the bacterium, the H.pylori urease enables the bacterium to survive in the acidic environment of the stomach. Recently, studies carried out on animal models have provided data suggesting that the urease is an important factor in the colonization of the gastric mucosa (Eaton et al. (1991) Infect. Immun. 59: 2470-2475). The urease is also suspected of causing injury, either directly or indirectly, to the gastric mucosa. Currently, Helicobacter pylori (H.pylori) is recognized as being the etiological agent of antral gastrites, and appears to be one of the cofactors required for the development of ulcers. Furthermore, it appears that the development of gastric carcinomas may be associated with the presence of H.pylori. Web site: http://www.delphion.com/details?pn=US06476213__

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dapE gene on Helicobacter pylori and dapE- mutant strains of Helicobacter pylori Inventor(s): Blaser; Martin J. (Nashville, TN), Karita; Mikio (Hofu, JP) Assignee(s): Vanderbilt University (nashville, Tn) Patent Number: 6,570,004 Date filed: December 9, 1999 Abstract: The invention provides the dapE gene of Helicobacter pylori and H. pylori dapE.sup.- mutants and to methods of using the mutants to express foreign genes and immunize against foreign agents. The dapE gene can consist of the nucleotide sequence defined in SEQ ID NO:3. Nucleic acids of the gidA gene and ORF 2 of H. pylori are provided. Examples of these nucleic acids can be found in SEQ ID NO:1 and SEQ ID NO:5, respectively. Having provided these nucleic acids, hybridizing nucleic acids in accord with the description of hybridizing nucleic acids of dapE are also provided. Excerpt(s): The invention pertains to the dapE gene of Helicobacter pylori and H. pylori dapE.sup.- mutants and to methods of using the mutants to express foreign genes and immunize against foreign agents. Helicobacter pylori are gram negative enteric bacteria that colonize the human gastric mucosa and cause gastritis and peptic ulcer disease (6,11,15) and are implicated in malignant neoplasms of the stomach (5,26,30,37). Thus, there exists a need for a method of treating and preventing H. pylori infection. The present invention meets these needs by providing the dapE gene of H. pylori and conditionally lethal mutants of H. pylori which can be used to express foreign proteins and to immunize against H. pylori infection. Web site: http://www.delphion.com/details?pn=US06570004__

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Detection of Helicobacter pylori in the stomach Inventor(s): Marshall; Barry (40 Beatrice Road, Dalkeith 6009, AU) Assignee(s): None Reported Patent Number: 6,479,278 Date filed: April 3, 2001 Abstract: A method for the in vivo detection of urease-producing helicobacter in the upper stomach is disclosed. The dense carrier is divided into two separate groups which are combined with separate reagent indicators, one of which also contains urea. The carriers are food soluble products, preferably sugar beads having a diameter of approximately 0.2 to 3.0 mm. The treated carriers and urea are encapsulated in a soluble capsule which is administered to a patient. The density of the carriers cause the capsule to migrate to the gastric mucosa, where the capsule, but not the reagents, is dissolved, placing the reagents and urea in direct contact with the gastric mucosa. The urea reacts with any urease present in the stomach by creating ammonia, which increases the pH in the immediate vicinity of the urea containing carrier and indicator beads. The two reagents react differently, through color change, to the increase in pH, which is viewed through use of an endoscope. A preferred first reagent is bromothymol blue (dibromothymolsulfonphthalein), which changes yellow in the presence of urease, and a preferred second reagent is phenol red (phenolsulfonphthalein), which turns red in the presence of urease. Excerpt(s): The instant invention relates to a novel method of in vivo diagnosis of upper gastrointestinal diseases. Factors adversely affecting the function of the gastrointestinal

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system in humans are exceedingly varied in their nature. Such disorders may arise in the upper or lower gastrointestinal tracts, or both. There is a broad range of causes of gastrointestinal disorders, including genetic, physiological, environmental and psychogenic factors. Accordingly, the diagnosis and management of these disorders can be exceptionally difficult. Among the chronic disorders of the upper gastrointestinal tract are those which fall under the general categories of gastritis and peptic ulcer disease. The upper gastrointestinal tract is generally defined as including the esophagus, the stomach, the duodenum, the jejunum and ileum. Peptic ulcers are lesions of the gastrointestinal tract lining, characterized by loss of tissue due to the action of digestive acids and pepsin. It has generally been held that peptic ulcers are caused by gastric hypersecretion, decreased resistance of the gastric lining to digestive acids and pepsin, or both. Gastritis is, by definition, an inflammation of the stomach mucosa. In practice, though, the disorder is manifested by a broad range of poorly-defined, and heretofore inadequately treated, symptoms such as indigestion, "heart burn", dyspepsia, and excessive eructation. Web site: http://www.delphion.com/details?pn=US06479278__ •

Double capsule for the administration of active principles in multiple therapies Inventor(s): Sanso; Giovanni (Milan, IT) Assignee(s): Axcan Pharma Inc. (quebec, Ca) Patent Number: 6,350,468 Date filed: June 16, 2000 Abstract: A pharmaceutical dosage form particularly suitable for the administration of active principles in multiple therapies is disclosed. The pharmaceutical dosage form is a double capsule where in an internal capsule is placed inside an external one. Each internal and external capsule includes one or more active principles. A double capsule according to the invention is preferably used in triple or quadruple therapies against the microorganisms Helicobacter Pylori. Advantages of this pharmaceutical dosage form consist in providing a simple posology for administration of two and more active principles, allowing the active principles to activate at the right intervals of time and in the preestablished quantities, and preventing interactions between active principles. In a preferred embodiment of the invention, the pharmaceutical dosage form has an external capsule containing bismuth subcitrate and metronidazole, and an internal capsule containing tetracycline and optionally omeprazole, which is used in therapy for eradication of Helicobacter pylori. Excerpt(s): This invention concerns a pharmaceutical dosage form consisting of a double capsule for the administration of active principles in multiple therapies. The double capsule consists in a capsule placed inside another one. Therapies for the administration of more than one active principle at a time or at short intervals of time are already well known. The most common pharmaceutical dosage form consists of tablets for the various active principles with coatings allowing the differentiated release of the chemical compounds. Among said therapies, the most common ones are those concerning affections of the digestive system caused by the presence of the microorganisms Helicobacter Pylori, such as gastritis and gastroduodenal ulcers, which in due time can lead to tumoral forms. As known, Helicobacter pylori is a modern appellation of Campilobacter pylori. Web site: http://www.delphion.com/details?pn=US06350468__

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Examination method of infection with Helicobacter pylori Inventor(s): Ito; Masaharu (Ibaraki-ken, JP), Kanemaki; Susumu (Kanagawa-ken, JP), Kobashi; Kyoichi (Toyama-ken, JP), Matsunobu; Kunitoshi (Kanagawa-ken, JP), Uono; Masanori (Kanagawa-ken, JP) Assignee(s): Eisai Co., Ltd. (tokyo, Jp), Gastec Corporation (kanagawa-ken, Jp) Patent Number: 6,312,918 Date filed: April 18, 1995 Abstract: There are described a simple examination method of infection with Helicobacter pylori possibly presenting in a gastric mucosa, and a device therefor. The examination is conducted by collecting gas in gastric cavity, and measuring mainly ammonia and additionally organic amines which are generated due to activities of the bacilli. The measurement is carried out by leading the gas in gastric cavity into oral cavity by vomiting-reflex, and sucking the gas by a metering suction pump through a gas detection tube to read-out a length of color-changed area in the gas detection tube. Excerpt(s): The present invention relates to a simple examination method of infection with Helicobacter pylori (hereinafter may also be abbreviated as "H.p.") which is a bacillus and may present in gastric mucosa, and a device therefor. According to the invention, the information on H.p.-infection and the activity of H.p. at the time of examination can be easily obtained. Because of the strongly acidic environment of the inside of the stomach, the gastric cavity had been considered unsuitable for the survival of bacilli since old times; however, about 100 years ago, the existence of spiral bacillus was observed and reported. The bacilli were formally discovered in the second half of the 1970's. In 1983, the bacilli were firstly isolated from gastric mucosa by Waren et al., and was named at first as "Campylobacter pyloridis, because it morphologically and biologically resembled Campylobacter which is one or Salmonella enteritidis, in addition to the fact that it was isolated from gastric antral mucosa in the vicinity of the pylorus. Later, the name was once changed to Campylobacter pylori. The genetic name has been changed to "Helicobacter" based on its form, since the difference from Campylobacter became clear in 1989. Continuous effort has been made investigating the correlation between H.p. and diseases of the upper alimentary tract even since the bacilli were isolated at a high rate by Marshall et al. From patients with gastric ulcer, duodenal ulcer or chronic gastritis in 1984, and the association between the presence of the bacilli and these diseases has been reported ["The lancet", No. 8390, pages 1311-1314 (June 1984)]. Web site: http://www.delphion.com/details?pn=US06312918__

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Fas ligand-like protein, its production and use Inventor(s): Hikichi; Yukiko (Tsukuba, JP), Nishi; Kazunori (Tsukuba, JP), Shintani; Yasushi (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,590,090 Date filed: August 31, 2000 Abstract: This invention relates to a Fas ligand-like protein having an apotosis-inducing actibvity, etc. or its salt, a partial peptide of the protein or its salt; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein, a

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pharmaceutical composition comprising the protein, the partial peptide or its salt; and an antibody to the protein or the partial peptide. The protein, the partial peptide or its salt, and the DNA are useful as a prophylactic or therapeutic agent for cancer, viral infection, Helicobacter pylori infection, invasive staphylococcia, hepatitis, nephritis, bone disease, atherosclerosis or pain. The antibody can be used in assay of the protein, the partial peptide or its salt. The protein, the partial peptide or its salt is useful as a reagent for the screening for candidate medical compounds. Excerpt(s): The present invention relates to a novel fas ligand-like protein having an apotosis-inducing activity, etc. and a DNA coding for the protein. A multicellular organism maintains its homeostasis ingeniously by controlling the proliferation and death of its cells. In the course of ontogenesis, many cells are eliminated through apotosis, and even in a mature organism the cells constituting its tissues maintain their functional integrity balancing proliferation against death. Cell death in this context is generally termed "programmed cell death", which is known to occur through the process of apotosis which is morphologically distinguished from that of necrosis, the accidental cell death caused by physical and chemical factors. Apoptotic cell death is characterized by blebbing of the cell membrane, chromatin condensation and DNA fragmentation, with the affected cells being eventually removed by phagocytic cells such as macrophages for reutilization (International Review of Cytology, 68, 251-306, 1980). Many physiological and pathological events related to apotosis have been identified until now and many attempts made to diagnose, prevent, or treat various diseases through induction or inhibition of the process of apotosis (Science, 267, 1456-1462, 1995). Apotosis is one of the vital phenomena which are attracting more than usual attention in the pharmaceutical industries. Web site: http://www.delphion.com/details?pn=US06590090__ •

Food containing active strains for inhibiting infection and treating gastritis, gastric and duodenal ulcers Inventor(s): Baek; Young Jin (Seoul, KR), Heo; Cheol Seong (Chunan, KR), Kim; Hyung Soo (Granger, IN), Lee; Jeong Jun (Suwon, KR) Assignee(s): Korea Yakult Co. Ltd. (seoul, Kr) Patent Number: 6,491,956 Date filed: October 10, 2001 Abstract: Live strains of Lactobacillus acidophilus HY2177 and Lactobacillus casei HY2743 maintained in nutritious foods, such as yogurt, imbue them with prophylactic and/or therapeutic properties. Such foods are beneficial in the prevention and/or treatment of gastritis, duodenal and gastric ulcers caused by infection from Helicobacter pylori (also referred to as H. pylori). The properties of these bacteria are boosted by the addition of egg yolk containing antibodies specific to H. pylori antigen derived from "fractionated H. pylori" and may be administered as active strains alone in a food supplement, or the active strains may be combined with H. pylori-antibodies (IgY). Excerpt(s): A nutritional formulation in which non-toxic (to humans) bacteria thrive, is used to prevent and treat gastric disorders associated with Helicobacter pylori (also referred to as H. pylori) which are believed to be attacked by the non-toxic bacteria. Only particular strains of non-toxic comestible bacteria, when ingested by humans are effective against H. pylori. Optionally and preferably, the prophylactic and/or therapeutic effects of the comestible bacteria are boosted with egg yolk containing

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immunoglubins (antibodies) specific to H. pylori antigen (also referred to as "H. pyloriantibodies"). Much has been published regarding H. pylori which inhabits the human gastric mucosa. It is a gram-negative spiral rod-shaped bacterium having an outer membrane with four to six polar flagella which are sheathed and have bulbous ends; each H. pylori bacterium is about 0.85.mu.m (micrometer) in diameter with an average length of 2.9.mu.m. Known pathogenic (disease) factors of H. pylori are (i) urease (urea aminohydrolase) which is produced by the bacteria to allow it to thrive in a strong acid environment in the range from pH 1-3, (ii) flagella which provide the bacteria with mobility, and (iii) a protein-aceous outer membrane of the cells which membrane helps the cells to stick to the gastric mucosal cells. Survival of H. pylori relies upon creation of a relatively non-acidic microenvironment in the vicinity of the bacteria, and a relatively basic microenvironment is provided by the enzyme urease; the more basic the better, and the closer to neutral pH, the more difficult it is for the H. pylori to thrive. The ability to command a near-neutral microenvironment is an essential property of bacteria which effectively prevent and treat gastric disorders. A result of interaction of H. pylori on the mucous membrane is the stimulation of numerous cytokines. The predominant immune response to infection is the production of interleukin-8 (IL-8). IL-8-induced neutrophils or macrophages are a direct cause of gastritis. To date, treatment to subdue secretion of gastric acid, for example with H.sub.2 isolator, is deemed unsatisfactory over the long term due to recrudescence which is now countered with medicines which act directly on the H. pylori. Presently, trends in the fight against infection by H. pylori may be categorized as follows: (a) development of antibiotics showing a direct effect against H. pylori, (b) development of vaccines for H. pylori, and (c) using anti-H. pylori antibodies which allow the live H. pylori to be terminated. For prophylaxis, (b) and (c) are preferred. Web site: http://www.delphion.com/details?pn=US06491956__ •

Food for inhibiting infection and treating gastritis, gastric and duodenal ulcers Inventor(s): Heo; Cheol Seong (#305 304dong Daelip hansup apt, Chunan, Chungchungnamdo 330-160, KR), Kim; Hyun Mi (#202 728-11 Pungdukchunli, Sugieup, Yongin, Kyunggido 449-840, KR), Kim; Hyung Soo (52303 Brenton Hills Dr., Granger, IN 46530), Lee; Jung Lyoul (#904 302dong Daewon apt, chowonmayeul pyungchongdong Donganku, Anyang, Kyungkido, 431-070, KR) Assignee(s): None Reported Patent Number: 6,329,002 Date filed: February 7, 2000 Abstract: Live strains of Lactococcus sp. HY 49, Lactobacillus casei HY 2782, and Bifidobacterium longum HY 8001 maintained in nutritious foods, such as yogurt, imbue them with prophylactic and/or therapeutic properties. Such foods are beneficial in the prevention and/or treatment of gastritis, duodenal and gastric ulcers caused by infection from Helicobacter pylori (also referred to as H. pylori). The properties of these bacteria are boosted by the addition of egg yolk containing antibodies specific to H. pylori antigen derived from "fractionated H. pylori". Excerpt(s): A nutritional formulation in which non-toxic (to humans) bacteria thrive, is used to prevent and treat gastric disorders associated with Helicobacter pylori (also referred to as H. pylori) which are attacked by the non-toxic bacteria. Only particular strains of non-toxic comestible bacteria, when ingested by humans are effective against H. pylori. Optionally and preferably, the prophylactic and/or therapeutic effects of the

Patents 237

comestible bacteria are boosted with egg yolk containing immunoglubins (antibodies) specific to H. pylori antigen (also referred to as "H. pylori-antibodies"). Much has been published regarding H. pylori which inhabits the human gastric mucosa. It is a gramnegative spiral rod-shaped bacterium having an outer membrane with four to six polar flagella which are sheathed and have bulbous ends; each H. pylori bacterium is about 0.85.mu.m (micrometer) in diameter with an average length of 2.9.mu.m. Known pathogenic (disease) factors of H. pylori are (i) urease which is produced by the bacteria to allow it to thrive in a strong acid environment in the range from pH 1-3, (ii) flagella which provide the bacteria with mobility, and (iii) a proteinaceous outer membrane of the cells which membrane helps the cells to stick to the gastric mucosal cells. To date, treatment to subdue secretion of gastric acid, for example with H2 isolator, is deemed unsatisfactory over the long term due to recrudescence which is now countered with medicines which act directly on the H. pylori. Presently, trends in the fight against infection by H. pylori may be categorized as follows: (a) development of antibiotics showing a direct effect against H. pylori, (b) development of vaccines for H. pylori, and (c) using anti-H. pylori antibodies which allow the live H. pylori to be terminated. For prophylaxis, (b) and (c) are preferred. Web site: http://www.delphion.com/details?pn=US06329002__ •

Formulation comprising antibacterial substance and antiulcer substance Inventor(s): Akiyama; Yohko (Ibaraki, JP), Iwasa; Susumu (Tsuzuki-gun, JP), Nagahara; Naoki (Itami, JP), Nakao; Masafumi (Ikoma, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,319,904 Date filed: July 7, 1999 Abstract: The present invention includes a formulation which comprises an antibacterial substance and an antiulcer substance, wherein at least either of them is formulated into a gastrointestinal mucosa-adherent solid preparation. The formulation of the present invention shows long retention time in the gastrointestinal tract because of adhesion to the gastrointestinal tract mucosa, synergetically enhances the pharmaceutical effects of an antibacterial substance, specially antibiotic against Helicobacter pylori (HP) and an antiulcer substance, with very low doses of active ingredients, particularly the anti-HP antibiotic with low prevalence of side effects. The present agent is useful as an antiulcer agent, showing potent anti-HP activity. Excerpt(s): The present invention relates to a formulation which comprises an antibacterial substance and an antiulcer substance, wherein at least either of them is formulated into a gastrointestinal mucosa-adherent solid preparation. The formulation of the present invention is used as an antiulcer agent and for other purposes. Since the isolation of Helicobacter pylori (hereinafter also referred to as HP) in 1983 [Lancet, 1, 1273 (1983)], its association with gastritis and digestive ulcer has drawn attention. This is because HP is found at high positivity rates in chronic gastritis or gastric ulcer [American Journal of Gastroenterology, 82, 2283 (1987)], despite the fact that it is normally not found in the mucosa of healthy humans [APMIS, 96, 84 (1988)]. On the other hand, the development of H.sub.2 blockers and proton pump inhibitors (hereinafter also referred to as PPI) has resulted in markedly improved healing rates for gastric/duodenal ulcer. However, there are some contractile cases in which no improvement occurs despite the appropriate treatment using these drugs, posing major problems. According to a report of such cases of contractile gastric ulcer [Japanese

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Journal of Gastroenterology, 89, 571 (1992)], the HP positivity rate is extremely high, with a reduction in the amount of gastromucosal mucus attributable to the ammonia produced by HP. Also, there are some reports of sustained infection with HP which delays ulcer healing or which is involved in ulcer recurrence [Lancet, 335, 1233 (1990); New England Journal of Medicine, 328, 308 (1993)]. Judging from these many clinical findings, HP elimination is believed to be useful in early healing of ulcer or prevention of its recurrence. Web site: http://www.delphion.com/details?pn=US06319904__ •

Guanidinomethyl cyclohexane carboxylic acid ester derivatives Inventor(s): Fujiwara; Hiromichi (Itami, JP), Kamoda; Osamu (Itami, JP), Yanagi; Toshiharu (Itami, JP) Assignee(s): Teikoku Chemical Industries Co., Ltd. (osaka, Jp) Patent Number: 6,284,791 Date filed: February 28, 1997 Abstract: A compound represented by general formula (I-2) or a pharmaceutically acceptable acid-addition salt thereof, useful as an anti-microbial against Helicobacter pylori and as a medicinal composition for treating Helicobacter pylori infection, wherein Ar represents phenyl, biphenyl or naphthyl each having a at least one substituent selected from the group consisting of halogen, cyano, nitro, carboxy, C.sub.1 -C.sub.18 alkyl, C.sub.1 -C.sub.18 alkoxy, C.sub.3 -C.sub.18 cycloalkyl, C.sub.7 -C.sub.18 aralkyl, C.sub.8 -C.sub.18 arylalkenyl, C.sub.7 -C.sub.18 aralkyloxy, optionally substituted phenoxy, optionally substituted C.sub.2 -C.sub.19 alkoxycarbonyl, and optionally substituted C.sub.8 -C.sub.19 aralkyloxycarbonyl, provided the case where Ar represents phenyl substituted by halogen, cyano, nitro, carboxy, C.sub.1 -C.sub.18 alkyl, optionally substituted C.sub.2 -C.sub.19 alkoxycarbonyl or C.sub.8 -C.sub.19 aralkyloxycarbonyl is expected. Excerpt(s): The present invention is related to novel compounds comprising an antibacterial action, especially with a strong antibacterial action against helicobacter pylori, and pharmaceutically acceptable salts thereof, anti-helicobacter pylori agents comprising one or more compounds of the present invention, and also pharmaceutically compositions for anti-Helicobacter pylori comprising one or more compounds of the present invention and pharmaceutically acceptable carriers. The present invention is also related to methods of treatment for patients infected with helicobacter pylori comprising administration of an effective dose of one or more compounds of the invention to the patients, and usages of one or more compounds of the invention for preparation of a medicament for the treatment of helicobacter pylori. Helicobacter pylori has been an remarked bacterium for investing lesion of a stomach and duodenum for the report by Wallen and Marshal, in Australia, in 1983 (Lancet ii: 1437-1442 (1983)). It has been known that the helicobacter pylori is a helicoid microaerophile gramnegative bacillus, adjusts its life environment by producing urease, and lives in tunica mucosa of stomach and duodenum, and also causes or recauses inflammations or ulcerations. It was reported that the United States Public Health Research Institute presented the recommendation which means to use a combination of antiulcerative agents and antibacterial agents extermination of helicobacter pylori (Chem. Indust. Daily Rep. Heisei 6.7.18) because Helicobacter pylori is considered to be strong correlation with crisis and recurrence of peptic ulcer.

Patents 239

Web site: http://www.delphion.com/details?pn=US06284791__ •

Helicobactor catalase nucleotide sequences, their production and use Inventor(s): Hirayasu; Kazunari (Osaka, JP), Kawabata; Tomohisa (Osaka, JP), Sugiyama; Tosiro (2-5-302, MinamiSanjoNishi 25-chome, Chuo-ku, Sapporo, Hokkaido, JP 064), Tanaka; Takumi (Hyogo, JP) Assignee(s): Eisai Co., Ltd. (jp), Sugiyama; Tosiro (jp) Patent Number: 6,551,779 Date filed: March 20, 2000 Abstract: Disclosed are amino acid sequences of polypeptides reacting with antibodies to Helicobacter pylori (HP), DNAs coding therefor, vectors containing said DNAs, transformants containing said vectors, a method for preparing said polypeptides by cultivating said transformants, and anti-HP antibody assaying reagents and HP gene detecting reagents comprising said polypeptides, thereby enabling specific, quantitative inspection of HP. Excerpt(s): The present invention relates to polypeptides, DNAs coding for said polypeptides, recombinant vectors containing said DNAs, host cells transformed with said recombinant vectors, a method for preparing said polypeptides by cultivating said host cells, and use thereof. Helicobacter pylori (which has previously been known as Campylobacter pylori) is a Gram-negative bacillus discovered from a chronic gastritis biopsy specimen as a spiral bacterium in 1983 [J. R. Warren and B. Marshall, Lancet, i, 1273 (1983)]. After the discovery thereof, the significance of this bacterium to chronic gastritis and duodenal ulcer has attracted attention, and investigation thereof has become one of important themes biologically and medically. In particular, elucidation of the mechanisms of cell injuries leading to diseases and developments of new inspection methods have been gained attention. Web site: http://www.delphion.com/details?pn=US06551779__

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Immunogenic compositions against helicobacter infection, polypeptides for use in the compositions, and nucleic acid sequences encoding said polypeptides Inventor(s): Ferrero; Richard L. (Paris, FR), Labigne; Agnes (Bures sur Yvette, FR), Suerbaum; Sebastien (Bochum, DE), Thiberge; Jean-Michel (Plaisir, FR) Assignee(s): Institut Pasteur (paris, Fr) Patent Number: 6,248,330 Date filed: May 2, 1995 Abstract: There is provided an immunogenic composition capable of inducing protective antibodies against Helicobacter infection characterized in that it comprises:i) at least one sub-unit of a urease structural polypeptide from Helicobacter pylori, or a fragment thereof, said fragment being recognized by antibodies reacting with Helicobacter felis urease, and/or at least one sub-unit of a urease structural polypeptide from Helicobacter felis, or a fragment thereof, said fragment being recognized by antibodies reacting with Helicobacter pylori urease;ii) and/or, a heat shock protein (Hsp), or chaperonin, from Helicobacter, or a fragment of said protein.The preparation, by recombinant means, of such immunogenic compositions is also provided.

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Excerpt(s): The present invention relates to immunogenic compositions for inducing protective antibodies against Helicobacter spp. infection. It also relates to proteinaceous material derived from Helicobacter, and to nucleic acid sequences encoding them. Antibodies to these proteinaceous materials are also included in the invention. H. pylori is a microorganism, which infects human gastric mucosa and is associated with active chronic gastritis. It has been shown to be an aetiological agent in gastroduodenal ulceration (Peterson, 1991), and two recent studies have reported that persons infected with H. pylori had a higher risk of developing gastric cancer (Nomura et al., 1991; Parsonnet et al., 1991). In vivo studies of the bacterium, and consequently, work on the development of appropriate preventive or therapeutic agents, has been severely hindered by the fact that Helicobacter pylori only associates with gastric-type epithelium from very few animal hosts, none of which are suitable for use as laboratory models. Web site: http://www.delphion.com/details?pn=US06248330__ •

Method and compositions for the control or eradication of Helicobacter pylori Inventor(s): Costin; James C. (Lower Gwynedd, PA) Assignee(s): Medpointe Healthcare Inc. (somerset, Nj) Patent Number: 6,555,534 Date filed: March 10, 1999 Abstract: The use of 4,4-methylenebis (tetrahydro-1,2-4-thiadiazine-1,1 -dioxide) in the eradication and control of the microorganism Helicobacter pylori in humans is disclosed. Excerpt(s): This invention relates to a method and compositions for the treatment of bacterial infection which reduces or eliminates the presence of bacteria. Moreover, this invention relates to a method and compositions for the reduction or elimination of Helicobacter pylori. Specifically, the present invention relates to the use of 4,4' methylenebis(tetrahydro-1,2,4-thiadiazine-1,2-dioxide) known generically as taurolidine to treat bacterial infections, particularly Helicobacter pylori infections. Taurolidine occurs as a white to off-white powder having the molecular formula -- C.sub.7 H.sub.16 N.sub.4 O.sub.4 S.sub.2. Web site: http://www.delphion.com/details?pn=US06555534__

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Method for detecting Helicobacter pylori infection Inventor(s): Blume; Richard S. (240 Main St., Northport, NY 11768) Assignee(s): None Reported Patent Number: 6,677,129 Date filed: January 3, 2000 Abstract: A method for oral sampling and rapid, specific detection of the urease activity associated with H. pylori infection in humans without the need for sample incubation. The method involves the steps of gargling, or gargling and rinsing the mouth with a measured volume of sampling liquid with known characteristics; retrieving an oral liquid sample 10 into a collection container 12; acidifying the oral liquid sample; and contacting the oral liquid sample within the collection container with a urease detecting

Patents 241

pad 14 containing urease substrate for detection of urease activity present in the oral liquid sample. The urease detecting pad can contain pH indicator for visual identification of color change associated with presence of urease activity in the oral liquid sample. The method provides for sampling of both the pharynx and mouth of the human, either separately or combined for diagnosis. pH change of the oral liquid sample associated with placing of the urease detecting pad onto the sample provides an additional or separate indicator of the presence of urease activity in the oral liquid sample. Excerpt(s): The present invention relates generally to health care diagnostics and specifically to an improved method for oral sampling in a human subject for rapid detection of the presence of infection, the specific embodiment being the detection of the urease activity associated with Helicobacter pylori infection in the human. Helicobacter pylori (H. pylori) is a common pathogen in humans and specifically causes disease of the stomach. In industrialized countries, infection can be present in half of all persons older than 50 years. First identified in 1983, H. pylori is now known to cause chronic gastritis or inflammation of the stomach, as well as gastric and duodenal ulcers. It is also associated with gastric malignancy (Thomas, E., et al., "The role of the oral cavity in Helicobacter pylori infection," Am. J. Gastroenterol., 1997 December; 92(12): 2148-2154). This and other publications cited are incorporated by reference herein. Combinations of antibiotics and bismuth and/or gastric acid blocking agents are used to treat H. pylori infection in the stomach. Bismuth salicylate inhibits the urease activity of H. pylori (Prewett, E., et al., "Comparison of one-day oral dosing with three bismuth compounds for the suppression of Helicobacter pylori assessed by the 13C-urea breath test," Aliment. Pharmacol. Ther., 1992 February; 6(1): 97-102). Web site: http://www.delphion.com/details?pn=US06677129__ •

Method for eradication of Helicobacter pylori Inventor(s): Borody; Thomas Julius (144 Great North Road, Five Dock, NSW 2046, AU) Assignee(s): None Reported Patent Number: 6,489,317 Date filed: November 20, 2000 Abstract: The invention provides methods for the treatment and/or prevention of recurrence of a gastrointestinal disorder associated with Helicobacter pylori in a patient requiring said treatment and/or prevention, which comprise administering to the patient a therapeutically effective amount of a first antibiotic which is an ansamycin and a therapeutically effective amount of at least a second antibiotic or antimicrobial agent. The invention also provides pharmaceutical compositions for use in the methods of the invention. Excerpt(s): This invention relates to pharmaceutical compositions and therapeutic methods for the treatment and/or prevention of recurrence of gastrointestinal disorders associated with infection by Helicobacter pylori (H. pylori). Helicobacter pylori has been found to cause chronic histological gastritis and peptic ulcer disease, such as gastric and duodenal ulcer. It also appears to cause a condition called non-ulcer dyspepsia where Helicobacter pylori causes inflammation in the stomach which is histologically associated with indigestion and epigastric pain. Helicobacter pylori is also thought to have a role in the causation of stomach cancer and its eradication may be instrumental in causing cure of ulcer disease, a reversal of a proportion of patients with

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non-ulcer dyspepsia, and prevention of gastric cancer development in those who may be predisposed to it. Until recent times, H. pylori has been found to be difficult to eradicate using known chemotherapeutic agents. Although many antibiotics can suppress H. pylori growth in vivo the mucosal concentration appears to be inadequate and penetration of the usual gastric mucus layer is poor. Furthermore, there is frequently more than one infecting agent within the mucosa and hence, sensitivities of the various bacteria may vary within one patient and within one region of the mucosa. The development of adequate in vivo eradication methods for chronic H. pylori infection has therefore been difficult. Furthermore, single antibiotics are almost never adequate for use and double antibiotic combinations have also resulted in poor eradication rates. A further major looming problem progressively affecting current eradication therapies is the rapid development of clarithromycin resistance worldwide. The proportion of H. pylori infections which are resistant to clarithromycin is increasing by from 2-5% per year. Resistance is developing faster in the countries where clarithromycin is being used frequently; in particular, USA and Europe. Hence, new methods for eradication of H. pylori are urgently required. In addition, salvage therapies for patients who have failed first time therapy are also unavailable and such treatments are becoming in demand as more and more patients undergo therapy and fail initial eradication attempts. Web site: http://www.delphion.com/details?pn=US06489317__ •

Method for screening the risk of gastric cancer Inventor(s): Harkonen; Matti (Espoo, FI) Assignee(s): Biohit Oyj (helsinki, Fi) Patent Number: 6,696,262 Date filed: March 14, 2001 Abstract: Method for screening the risk for gastric cancer using, in combination, the determination of serum pepsinogen I, gastrin-17 and the supporting determination of Helicobacter pylori antibodies from blood serum, in order to detect either atrophy of the corpus area, atrophy of the antrum area or atrophy of the mucosa of the whole stomach as well as a causative Helicobacter pylori infection, whereby the risk for gastric cancer can be evaluated and the necessary gastroscopy and follow-up can be planned. Excerpt(s): In the following background information is presented relating to methods for screening for the risk of gastric cancer, primarily using pepsinogen I and gastrin-17 determination from a blood sample. Although the occurrence of new cases of gastric cancer has diminished in the recent years, gastric cancer is still one of the most common malignancies. In Finland, approximately 250 to 300 new cases of cancer/one million people/year are registered. In the age group of people above 50, there are an estimated 2350 cases of stomach cancer, which is about 3 per mille of the age group population (Finnish Cancer Registry--The Institute for Statistical and Epidemiological Cancer Research 1993). In addition to Finland, there is a high gastric cancer incidence in Iceland, South America and especially in Japan. The prognosis of gastric cancer is usually poor, as there is no specific treatment. Presently the only possibility of successfully treating gastric cancer is its early detection and total removal surgically. Web site: http://www.delphion.com/details?pn=US06696262__

Patents 243

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Methods for controlling gram negative bacteria in mammals with bicyclo spiroether compounds Inventor(s): Berkowitz; Barry (Framingham, MA), Blackburn; Chris (Natick, MA), Sachs; George (Encino, CA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,271,256 Date filed: November 30, 1999 Abstract: Methods for controlling growth of gram negative bacteria, such as Helicobacter pylori, which are agents associated with disorders of the gastrointestinal tract of a mammal are described. They include administering a therapeutically effective amount of a polyether ionophore antibiotic to a mammal, such that growth of gram negative bacteria which are agents associated with disorders of the gastrointestinal tract of a mammal is controlled. Packaged pharmaceutical compositions for controlling gram negative bacteria are also described. The packaged compositions include a container holding a therapeutically effective amount of a pharmaceutical composition for controlling gram negative bacteria which are agents associated with disorders of the gastrointestinal tract of a mammal and instructions for using the pharmaceutical composition for control of the gram negative bacteria, such that growth of gram negative bacteria which are agents associated with disorders of the gastrointestinal tract of a mammal is controlled. The pharmaceutical composition includes at least one polyether ionophore antibiotic or a bicyclic spiroether. Excerpt(s): Helicobacter pylori bacterial infections are a serious problem in humans. They have been shown to be a strong causative factor in gastric ulcer disease, such as stomach ulcers and small intestine ulcers which can result in death. Helicobacter pylori is a gram-negative, S-shaped, microaerophilic bacterium that was discovered and cultured from a human gastric biopsy specimen. (Warren, J. R. and B. Marshall, (1983) Lancet 1: 1273-1275; and Marshall et al., (1984) Microbios Lett. 25: 83-88). H. pylori bacterial cells can survive in a low pH environment because of an enzyme on their outer cell wall called urease. Urease converts urea in the stomach into bicarbonate and ammonia. The bicarbonate and ammonia neutralize the acid gastric juices, thereby providing a protective layer around the H. pylori. Since H. pylori are gram-negative rod type bacteria, it is difficult to treat H. pylori infections without using agents that will also affect other gram-negative bacteria elsewhere in the body. H. pylori has been strongly linked to chronic gastritis and duodenal ulcer disease. (Rathbone et. al., (1986) Gut 27: 635-641). Moreover, evidence is accumulating for an etiologic role of H. pylori in nonulcer dyspepsia, gastric ulcer disease, and gastric adenocarcinoma. (Blaser M. J., (1993) Trends Microbiol. 1: 255-260). Transmission of the bacteria occurs via the oral route, and the risk of infection increases with age. (Taylor, D. N. and M. J. Blaser, (1991) Epidemiol. Rev 13: 42-50). H. pylori colonizes the human gastric mucosa, establishing an infection that usually persists for decades. Infection by H. pylori is prevalent worldwide. Developed countries have infection rates over 50% of the adult population, while developing countries have infection rates reaching 90% of the adults over the age of 20. (Hopkins R. J. and J. G. Morris (1994) Am. J. Med. 97: 265-277). The bacterial factors necessary for colonization of the gastric environment, and for virulence of this pathogen, are poorly understood. Examples of the putative virulence factors include the following: urease, an enzyme that may play a role in neutralizing gastric acid pH (Eaton et al., (1991) Infect. Immunol. 59: 2470-2475; Ferrero, R. L. and A. Lee (1991) Microb. Ecol. Hlth. Dis. 4: 121-134; Labigne et al., (1991) J. Bacteriol. 173: 1920-1931); the bacterial flagellar proteins responsible for motility across the mucous layer (Hazell et al., (1986) J.

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Inf. Dis. 153: 658-663; Leying et al., (1992) Mol. Microbiol. 6: 2863-2874; and Haas et al., (1993) Mol. Microbiol. 8: 753-760; Vac A), a bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells (Schmitt, W. and R. Haas, (1994) Molecular Microbiol. 12(2: 307-319) and several gastric tissue-specific adhesions (Boren et al., (1993) Science 262: 1892-1895; Evans et al., (1993) J. Bacteriol. 175: 674-683; and Falk et al., (1993) Proc. Natl. Acad. Sci. USA 90: 2035-2039). Web site: http://www.delphion.com/details?pn=US06271256__ •

Moenomycin and its derivatives for the production of pharmaceuticals, and pharmaceuticals containing moenomycin or its derivatives Inventor(s): Hedtmann; Udo (Frankfurt, DE), Riess; Gunther (Hattersheim, DE), Seibert; Gerhard (Darmstadt, DE) Assignee(s): Aventis Pharma Deutschland Gmbh (frankfurt AM Main, De) Patent Number: 6,242,424 Date filed: November 28, 1994 Abstract: Moenomycin and its derivatives are suitable for the production of pharmaceuticals for the treatment of gastric ulcers and for the control of Helicobacter pylori. Excerpt(s): The present invention relates to moenomycin and its derivatives for the production of pharmaceuticals, and pharmaceuticals containing moenomycin or its derivatives. The present invention is based on the object of finding an effective medicament for the control of gastric ulcers and for the prophylaxis of cancer of the stomach. Hitherto, e.g. so-called antacids and, with particular success, H.sub.2 -receptor blockers were used in the indication area mentioned. Furthermore, it was already known that Helicobacter pylori infections are frequently responsible for stomach disorders. Infection of the human stomach with the pathogenic gram-negative bacterium Helicobacter pylori causes temporary dyspeptic symptoms. H. pylori is additionally the underlying pathogen in the chronically active type b gastritis and a significant risk factor for the occurrence of cancer of the stomach. The pathophysiological mechanisms by which H. pylori causes diseases of the stomach are still relatively unclear. It is known that the microorganism produces a number of potentially toxic enzymes and chemicals (urease, ammonia, vacuolizing cytotoxin). The persistence of the bacterium and the lasting antigenic stimulus are probably the cause of the long-term destruction of the gastric mucous membrane. Web site: http://www.delphion.com/details?pn=US06242424__

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Strain of Lactobacillus gasseri Inventor(s): Hirata; Haruhisa (Hadano, JP), Kimura; Katsunori (Tokorozawa, JP), Koga; Yasuhiro (Isehara, JP) Assignee(s): Meiji Dairies Corporation (tokyo, Jp) Patent Number: 6,596,530 Date filed: September 22, 2000 Abstract: A food or drink product with a disinfection property of Helicobacter pylori and/or a protection property against infection with H. pylori, comprising as the

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effective ingredient Lactobacillus gasseri OLL 2716 (FERM BP-6999) with a high disinfection potency of H. pylori.The food or drink product prepared by using the lactic acid bacterium, such as acid milk and the like, is suitable for long-term ingestion as a food or drink product with a disinfection property of H. pylori and/or a protection property against infection with H. pylori. Excerpt(s): The present invention relates to Lactobacillus gasseri (sometimes referred to as L. gasseri hereinafter) with an effect on the disinfection of Helicobacter pylori (sometimes referred to as H. pylori hereinafter) and/or the protection against infection with H. pylori, and a food or drink product containing the lactic acid bacterium. Since the discovery of H. pylori as a bacterium living in stomach in 1983 by Warren et al. [Lancet, I. 1273 (1983)], attention has been focused on the relation with chronic gastritis, gastric ulcer and duodenal ulcer. Recently, it has been evidenced that gastric gland cancer occurs in mongolian gerbil infected with H. pylori, with no administration of any carcinogenic substance [Watanabe et al., Gastroenterology, 115; 642 (1988)] and the relation of H. pylori with gastric cancer has also been suggested as one etiological bacterium thereof. Meanwhile, it is increasingly indicated that the disinfection of H. pylori in H. pylori-positive patients with digestive ulcer can suppress the recurrence of digestive ulcer and therefore, active disinfection therapy of H. pylori has been practiced in European counties and the U.S. As to the method for disinfecting H. pylori, a combination method of antibiotics (.beta.-lactams, aminoglycosides, macrolides, tetracyclines and the like) and antiulcerative agents is general; for example, a combination therapy of three drugs, namely two types of antibiotics (clarithromycinmetronidazole or amoxycilin) and a proton pump inhibitor (PPI) suppressing the secretion of gastric acid, is clinically practiced. However, the most serious drawback of the administration of drugs such as antibiotics for the purpose of the disinfection therapy is the increase of the frequency of the occurrence of drug-resistant H. pylori and the occurrence of severe side effects such as diarrhea and allergy and the like, due to the multiple combination of high-dose drugs. Web site: http://www.delphion.com/details?pn=US06596530__ •

Therapeutic method and apparatus for debilitating or killing microorganisms within the body Inventor(s): Ganz; Robert A. (1431 Lakeview Ave., Minneapolis, MN 55416) Assignee(s): None Reported Patent Number: 6,464,625 Date filed: June 23, 1999 Abstract: A treatment method and apparatus for debilitating or killing Helicobacter pylori or other microorganisms within the body of a patient is especially suited for treating stomach or duodenal ulcers. The present therapeutic method involves the use of ionizing radiation for eliminating pathogenic microorganisms within or supported upon the lining of a body cavity of a patient, e.g., the stomach. An elongated flexible shaft is provided for insertion into the body in any of various ways selected by the surgeon. It can be placed endoscopically, e.g., through the esophagus, placed surgically, placed laparoscopically or by CAT scan-guided percutaneous insertion. A radiant energy distribution head is provided at the end of the flexible shaft to transmit ionizing radiation for destroying microorganisms within the body. Radiant energy, e.g., x-ray, ultraviolet light, beta radiation, gamma radiation, radio waves, microwaves, or infrared energy, is then transferred from the head of the instrument to the epithelium around the

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head of the instrument in an amount sufficient to debilitate or kill the Helicobacter pylori or other microorganisms in the lining of the body cavity. Excerpt(s): This invention relates to a method and apparatus for the destruction of microorganisms on or within a body cavity of a patient through the use of ionizing radiation. Infections involving the human gastrointestinal tract are extremely common, involving many millions of people on an annual basis. These infections include bacteria, viruses, and fungi, and are responsible for significant illness, morbidity and, in many cases, death. While the invention has utility in destroying microorganisms in various parts of the body, e.g., the stomach, bowel, lungs, peritoneal cavity, urinary tract, etc., it is particularly useful in the treatment of gastrointestinal infections. It has recently been shown that the most common gastrointestinal infection in the world is due to Helicobacter pylori, a bacterial pathogen that infects the stomach and duodenum. In the United States, for example, Helicobacter pylori is found in approximately 20% of the adult population. It is a chronic gut infection and, once acquired, is notoriously difficult to cure. Most infectious bacteria can be readily destroyed by the human immune system; however, Helicobacter pylori lives in the lumen of the stomach and on the surfaces of the stomach and duodenal cells, making it relatively resistant to a host immune response, even if vigorous. The present invention, however, takes advantage of its location in the treatment method and apparatus employed in the present invention. Web site: http://www.delphion.com/details?pn=US06464625__ •

Use of 7-(1-aminomethyl-2-oxa-7-aza-bicyclo[3.3.0]oct-7-yl)-quinolone carboxylic acid and naphthyridone carboxylic acid derivatives for treating Helicobacter pylori infections and the gastroduodenal diseases associated therewith Inventor(s): Baasner; Bernd (Bergisch Gladbach, DE), Bartel; Stephan (Kurten, DE), Endermann; Rainer (Wuppertal, DE), Himmler; Thomas (Odenthal, DE), Jaetsch; Thomas (Koln, DE), Labischinski; Harald (Wuppertal, DE), Matzke; Michael (Wuppertal, DE), Petersen; Uwe (Leverkusen, DE), Schaller; Klaus (Wuppertal, DE), Schenke; Thomas (Bergisch Gladbach, DE), Werling; Hans-Otto (Wuppertal, DE) Assignee(s): Bayer Aktiengesellschaft (leverkusen, De) Patent Number: 6,288,081 Date filed: August 6, 1999 Abstract: The invention relates to the use of quinolone- and naphthyridonecarboxylic acid derivatives which are substituted in position 7 by a 1-aminomethyl-2-oxa-7azabicyclo[3.3.0]oct-7-yl radical, and of their salts for the therapy of Helicobacter pylori infections and associated gastroduodenal disorders. Excerpt(s): This application is a 371 of PCT/EP97/06751 filed on Dec. 3, 1997. The invention relates to the use of quinolone- and naphthyridonecarboxylic acid derivatives which are substituted in position 7 by a 1-aminomethyl-2-oxa-7-aza-bicyclo[3.3.0]oct-7yl radical, and of their salts for the therapy of Helicobacter pylori infections and associated gastroduodenal disorders. In the years following the rediscovery of Helicobacter pylori (H. pylori; old name Campylo-bacter pylori) by Warren and Marshall in 1983, the pathophysiological ideas on the genesis of gastro-duodenal disorders in man were developed further in a fundamental way. Web site: http://www.delphion.com/details?pn=US06288081__

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Patent Applications on Helicobacter Pylori As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Helicobacter pylori: •

Anti peptic ulcer activity of an extract of a plant flower woodfordia fruticosa Inventor(s): Banerjee, Sukdeb; (Kolkata, IN), Bhattacharya, Samir; (Kolkata, IN), Das, Pratap K.; (Kolkata, IN), Goswami, Suchandra; (Kolkata, IN), Sahu, Niranjan P.; (Kolkata, IN), Sett, Suchandra; (Kolkata, IN) Correspondence: Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20040022875 Date filed: March 27, 2003 Abstract: The present invention provides a pharmaceutical composition comprising an effective amount of an extract or lyophilized extract or at least one bioactive fraction obtained from plant woodfordia ftuticosa along with one or more pharmaceutically acceptable additives/carriers for treating ulcer caused by the conditions such as stress induced ulcer, peptic ulcer, cold restraint induced ulcer, drug induced ulcer and acid induced ulcer, also used as specific inhibitor of gastric H.sup.+,K.sup.+-ATPase and anti-Helicobacter pylori activity. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119 of provisional application Serial No. 60/367,490, filed Mar. 27, 2002, hereby expressly incorporated by reference. This application is also a continuation of said '490 provisional. Traditional herbal preparations are known for centuries to protect against peptic ulcer diseases, the aetiopathological basis of which were not known in those periods. Current day knowledge about the underlying biochemical mechanism for most of the gastric ulcers and majority of the duodenal ulcers deserve appropriate consideration and due weightage while consolidating the claim regarding the efficacy of a plant extract. In a Program on `Discovery, Development & Commercialization of New Bioactive & Traditional Preparations`, coordinated by Council of Scientific Research, the Applicant has been collecting, extracting & screening different potential plants and their parts for their bioefficay against various diseases. Gastric ulcer is one such disease. Based on screening through appropriate experimental model(s), the applicant has selected a plant flower as our target for the development of an effective anti ulcer medicine. This invention envisages to claim the potential of an extract obtained from the flower of Woodfordia fruticosa to act as an effective therapy against peptic ulcer diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

9

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

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Antimicrobial agent Inventor(s): Hadano, Makoto; (Tokyo, JP), Sato, Masaru; (Saitama, JP) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20030069279 Date filed: May 15, 2002 Abstract: The present invention relates to an antimicrobial agent for preventing, ameliorating and treating diseases attributable to Helicobacter pylori, for example peptic ulcer and gastritis, particularly recurring peptic ulcer and recurring gastritis, and provides (1) an antimicrobial agent comprising oxethazaine represented by the following formula as an active ingredient, (2) an antimicrobial agent comprising oxethazaine and a proton pump inhibitor as active ingredients, and (3) an antimicrobial agent comprising oxethazaine and an antibiotic as active ingredients. 1 Excerpt(s): The present invention relates to an antimicrobial agent for preventing, ameliorating and treating diseases caused by the microaerophilic Gram-negative spiral and short bacillus Helicobacter pylori (H. pylori), for example peptic ulcer and gastritis, particularly recurring peptic ulcer and gastritis. Conventionally, a large number of medicines have been used as anti-ulcer agents for preventing, ameliorating and treating peptic ulcer such as gastric ulcer and duodenal ulcer, and recently, histamine H.sub.2receptor antagonists among these medicines are mainly used. By the advent of histamine H.sub.2-receptor antagonists, it became possible to rapidly ameliorate and treat peptic ulcer and gastritis, particularly with respect to subjective symptoms. However, in the treatment of peptic ulcer or gastritis by the conventional anti-ulcer agents containing histamine H.sub.2-receptor antagonists, there is the problem that ulcer recurs highly frequently when chemotherapy is suspended after the recovery. Because the reason for this recurrence has not been revealed for a long time, none of effective prophylactic and therapeutic methods have been established. Meanwhile, it was shown from 1979 onward that the microaerophilic Gram-negative spiral and short bacillus H. pylori is present in gastric mucosa of patients suffering from peptic ulcer and bacterium has a close relationship with gastritis and gastric ulcer. It, formerly classified as Campylobacter pylori (C. pylori), was newly designated H. pylori in re-consideration in microbial taxonomy in 1989, and thus C. pylori and H. pylori are the same bacterium although it may be referred to as C. pylori in some literatures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Anti-microbial-adhesion fraction derived from vaccinium Inventor(s): Goldhar, Janina; (Tel Aviv, IL), Kashman, Yoel; (Tel Aviv, IL), Ofek, Itzhak; (Givataun, IL), Sharon, Nathan; (Tel Aviv, IL), Weiss, Ervin; (Herzeliya, IL) Correspondence: Kohn & Associates; Suite 410; 30500 Northwestern Highway; Farmington Hills; MI; 48334; US Patent Application Number: 20020048611 Date filed: July 27, 2001 Abstract: A non-food anti-microbial-adhesion and aggregation composition comprising a suitable carrier and an effective amount of an adhesion inhibitory fraction isolated from juice from berries of the Vaccinium plant genus. In an embodiment the anti-

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aggregation and adhesion fraction is isolated from cranberry juice. It is characterized as being polymeric and having a molecular weight.gtoreq.14,000; an elemental analysis of carbon 43-51%, hydrogen 4-5%, no nitrogen, no sulfur and no chlorine; a nuclear magnetic resonance (NMR) line spectrum as set forth in FIGS. 2A and 2B; and an ultraviolet spectrum with an absorption peak at 280 nm in neutral or acidic pH solution which is absent in alkali solutions. This fraction exhibits adhesion inhibitory activity against P fimbriated bacteria, oral bacteria and Helicobacter pylori. Excerpt(s): This application is a Continuation-In-Part of U.S. Ser. No. 08/772,021, filed Dec. 19, 1996. This invention relates to plant extracts having therapeutic and other uses, and more specifically to an extract of juice from berries of the Vaccinium plant genus having an anti-microbial-adhesion activity. Adhesion of the bacteria to each other (intraspecies) and to other bacterial species (intergeneric coaggregation) as well as to host tissues and cells contributes significantly to disease progression and pathology as for example in dental caries and plaque as well as in the persistance of Helicobacter pylori infection. It would therefore be useful to have compounds which can interrupt microbial adhesion and aggregation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti-sigma28 factors in Helicobacter pylori, Campylobacter jejuni and Pseudomonas aeruginosa and applications thereof Inventor(s): Colland, Frederic; (Fosses, FR), De Reuse, Hilde; (Paris, FR), Labigne, Agnes; (Bures-sur-yvette, FR), Legrain, Pierre; (Paris, FR), Rain, Jean-Christophe; (Puteaux, FR) Correspondence: Lerner, David, Littenberg,; Krumholz & Mentlik; 600 South Avenue West; Westfield; NJ; 07090; US Patent Application Number: 20020192796 Date filed: January 31, 2002 Abstract: Disclosed are polypeptides named HP1122, Cj1464 and PA3351 which are the anti-.sigma.sup.28 factor of Helicobacter pylori, Campylobacter jejuni and Pseudomonas aeruginosa, respectively and fragments and variants thereof. Also disclosed is a polypeptide named SID1122 which is the domain of Helicobacter pylori's HP1122 polypeptide involved in a specific interaction with Helicobacter pylori.sigma.sup.28 (HP1032) and which has an anti-.sigma.sup.28 factor activity. Further disclosed are a SID1122 polypeptide that interacts with HP1032, identification of the HP1032 interacting domain (SID1032) that is specifically involved in the interaction with HP1122, complexes of two polypeptides such as HP1122-HP1032, or SID1122SID1032, fragments and variants of the SID1122 and SID1032 polypeptides, antibodies to the SID1122 and SID1032 polypeptides, methods for screening drugs or agents which modulate the interaction of Helicobacter pylori's polypeptides encoded by HP1122 and HP1032, and pharmaceutical compositions for treating or preventing Gram negative flagellated bacteria infection in a human or mammal, more specifically Helicobacter sp. or Campylobacter jejuni or Pseudomonas aeruginosa infection, in particular Helicobacter pylori infection in a human or a mammal. Excerpt(s): The present application claims priority to U.S. provisional application No. 60/265,465 filed Jan. 31, 2001. Helicobacter pylon (H. pylori) is a microaerophilic, Gram negative, slow growing spiral shaped and flagellated organism. H. pylori has first been isolated in 1984 from a gastric biopsy specimen of a patient with chronic gastritis

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(Marshall and Warren, 1984). The organization of the physical structure of the H. pylori flagellum is similar to that of enteric organisms Escherichia coli and Salmonella typhimurium. The flagellum is composed of three structural elements: a basal body, a flexible hook and a flagellar filament. The mechanism of gene expression involved in flagellar assembly was extensively studied in the model organisms mentioned above (for review, see Macnab et al., 1996). In E. coli and S. typhimurium genes involved in flagellar biosynthesis are expressed in a hierarchical order and divided into three classes: (i) the class 1 genes, flhC and flhD, are regulated by the.sigma.sup.70 factor of RNA polymerase. The FlhC and FlhD proteins act as transcriptional activators to stimulate transcription from class 2 genes; (ii) the class 2 genes encode the early components required for flagellar assembly such as the basal body and flexible hook (HBB complex) as well as the.sigma.sup.28 factor of RNA polymerase; and (iii) the expression of the class 3 genes, which encode proteins involved in the final stages of flagellar assembly, is controlled by the.sigma.sup.28 factor. Completion of the HBB complex is required to result in class 3 gene expression. This tight regulation is due to the presence of the anti-.sigma.sup.28 factor, FIgM, which binds to.sigma.sup.28 and prevents its association with RNA polymerase core enzyme (Ohnishi et al., 1992; for review, see Hughes & Mathee, 1998). It has been shown that FIgM is secreted from the cell through the HBB structures thus allowing RNA polymerase associated with.sigma.sup.28 to transcribe class 3 genes (Gillen & Hughes, 1991a; 1991b; Hughes et al., 1993; Kutsukake, 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bacterial antigens and vaccine compositions Inventor(s): Bolin, Ingrid; (Goteborg, SE), Svennerholm, Ann-Mari; (Vastra Frolunda, SE) Correspondence: White & Case Llp; Patent Department; 1155 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20020168726 Date filed: September 15, 1999 Abstract: The present invention relates to recombinant polypeptides which constitute Helicobacter pylori surface-exposed antigens with an approximate molecular weight of 29 kDa. The invention furthermore provides nucleic acid molecules coding for the said polypeptides, as well as vectors and host cells comprising such nucleic acid molecules. The said recombinant polypeptides are useful for the diagnosis of H. pylori infections and for the manufacture of vaccine compositions which will elicit a protective immune response against such infections, said vaccine compositions being suitable for both therapeutic and prophylactic use. Excerpt(s): The present invention provides recombinant polypeptides which constitute Helicobacter pylori antigens, said antigens being expressed on the surface of both dividing (bacillary) forms as well as resting (coccoid) forms of H. pylori, and giving rise to both systemic and local (mucosal) production of antibodies. The invention furthermore provides nucleic acid molecules coding for the said polypeptides, as well as vectors and host cells comprising such nucleic acid molecules. The said recombinant polypeptides are useful for the diagnosis of H. pylori infections and for the manufacture of vaccine compositions which will elicit a protective immune response against such infections, said vaccine compositions being suitable for both therapeutic and prophylactic use. The gram-negative bacterium Helicobacter pylori is an important

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human pathogen, involved in several gastroduodenal diseases. Colonization of gastric epithelium by the bacterium leads to active inflammation and progressive chronic gastritis, with a greatly enhanced risk of progression to peptic ulcer disease. In order to colonize the gastric mucosa, H. pylori uses a number of virulence factors. Such virulence factors comprise several adhesins, with which the bacterium associates with the mucus and/or binds to epithelial cells; ureases which helps to neutralize the acid environment, and proteolytic enzymes which makes the mucus more fluid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Benzimidazole compounds, process for producing the same and use thereof Inventor(s): Kamiyama, Keiji; (Osaka, JP), Sato, Fumihiko; (Osaka, JP) Correspondence: Takeda Pharmaceuticals North America, Inc; Intellectual Property Department; 475 Half Day Road; Suite 500; Lincolnshire; IL; 60069; US Patent Application Number: 20040039027 Date filed: April 9, 2003 Abstract: A compound represented by the formula (I) 1wherein each symbol is as defined in the specification, or a salt thereof (1) shows a superior anti-ulcer activity, a gastric acid secretion-suppressive action, a mucosa-protecting action, an antiHelicobacter pylori action and the like in living organisms, (2) shows low toxicity, (3) is stable to acid (which obviates the need to formulate an enteric-coated preparation, thereby lowering the cost, and reduces the size of preparation to facilitate swallowing for patients having difficulty in swallowing), (4) shows faster absorption than entericcoated preparations (rapid expression of gastric acid secretion-suppressive action), and (5) is sustainable. According to the present invention, a benzimidazole compound, which has superior stability to acid and which is converted to a proton pump inhibitor in living organisms to show an anti-ulcer activity and the like, can be provided. Excerpt(s): The present invention relates to a benzimidazole compound, which is converted to a proton pump inhibitor in living organisms and shows an anti-ulcer activity and the like, a production method thereof and use thereof. A proton pump inhibitor, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1Hbenzimidazole, and a salt thereof having an anti-ulcer activity are reported in JP-A-6150978 and the like. However, since the above-mentioned compounds are unstable to acids, for oral administration, they are formulated into an enteric-coated preparation, filled in a capsule and administered to prevent decomposition by gastric acid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Benzoamide piperidine containing compounds and related compounds Inventor(s): Arnold, Eric Platt; (Hebron, CT), Chappie, Thomas Allen; (Old Lyme, CT), Huang, Jianhua; (Waterford, CT), Humphrey, John Michael; (Mystic, CT), Nagel, Arthur Adam; (Gales Ferry, CT), O'Neill, Brian Thomas; (Old Saybrook, CT), Sobolov-Jaynes, Susan Beth; (Ivoryton, CT), Vincent, Lawrence Albert; (Moosup, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030087925 Date filed: March 16, 2001 Abstract: The present invention relates to certain benzoamide piperidine containing compounds and related compounds that exhibit activity as NK-1 receptor antagonists, (e.g., substance P receptor antagonists), to pharmaceutical compositions containing them, and to their use in the treatment and prevention of central nervous system disorders, inflammatory disorders, cardiovascular disorders, ophthalmic disorders, gastrointestinal disorders, disorders caused by helicobacter pylori, disorders of the immune system, urinary incontinence, pain, migraine, emesis, angiogenesis and other disorders. Excerpt(s): Substance P is a naturally occurring undecapeptide belonging to the tachykinin family of peptides, the latter being so-named because of their prompt stimulatory action on smooth muscle tissue. More specially, substance P is a pharmaceutically active neuropeptide that is produced in mammals (having originally been isolated from gut) and possesses a characteristic amino acid sequence that is illustrated by D. F. Veber et al. in U.S. Pat. No. 4,680,283. The wide involvement of substance P and other tachykinins in the pathophysiology of numerous diseases has been amply demonstrated in the art. World Patent Application WO 97/03066, published Jan. 30, 1997, and U.S. patent application Ser. No. 08/98004, filed May 9, 1996, refer to substituted benzolactam and cyclicthioamide compounds that exhibit activity as substance P receptor antagonists. Other substance P receptor antagonists containing a fused bicyclic moiety are referred to in the following: U.S. patent application Ser. No. 09/011,271, filed Jun. 10, 1996; U.S. Provisional Patent Application 60/132,858, filed May 6, 1999; U.S. patent application Ser. No. 09/402,630, filed Oct. 26, 1998; and World Patent Application WO 99/13663, published Jun. 23, 1994. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Chelate compound-containing antibacterial agent for helicobacter pylori Inventor(s): Nagai, Toshiro; (Tsukuba-shi, JP), Oita, Shigeru; (Zentsuji-shi, JP) Correspondence: Frishauf, Holtz, Goodman; Langer & Chick, P.C.; 25th Floor; 767 Third Avenue; New York; NY; 10017; US Patent Application Number: 20020058696 Date filed: March 8, 2001 Abstract: An antibacterial agent is provided, which has an action for inhibiting growth of Helicobacter pylori participating to occurrence of chronic gastritis and gastric ulcer, and a highly safe substance is used as an effective component therein. An antibacterial agent for Helicobacter pylori is characterized in that at least one substance selected

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from the group consisting of ethylenediaminetetraacetic acid and its metal salts is contained as an effective component. Excerpt(s): The present invention relates to an antibacterial agent for Helicobacter pylori, in more detail, to an antibacterial agent for Helicobacter pylori, said agent contains as an effective component a chelate compound, safety of which against human bodies is confirmed. Recently, it has been found that Helicobacter pylori is much participated to occurrence of chronic gastritis and gastric ulcer. In Japan, it is said that about 60 millions people corresponding to an about half of total populations are infected with Helicobacter pylori (Shokunokagaku, Vol. 265, pages 87-99, 2000). Cure of chronic gastritis and gastric ulcer can be attained by removing the bacterium from stomach by means of administration of antibiotics etc. However, there are some cases wherein the bacterium is hard to be removed depending on patients. Further, as to antibiotics, there are some problems concerning appearance of resistant bacteria and side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

CLONING AND CHARACTERIZATION OF THE FLBA GENE OF H. PYLORI, PRODUCTION OF AFLAGELLATE STRAINS Inventor(s): LABIGNE, AGNES; (BURES SUR YVETTE, FR), SUERBAUM, SEBASTIAN; (BOCHUM, DE) Correspondence: Finnegan Henderson Farabow; Garrett And Dunner; 1300 I Street N W; Washington; DC; 200053315 Patent Application Number: 20030152579 Date filed: January 29, 1998 Abstract: The present application relates to nucleotide sequences which regulate the biosynthesis of the flagella proteins Helicobacter pylori, to the proteins encoded by these sequences and to aflagellate bacterial strains. The invention also relates to the use of these means for detecting an infection due to H.pylori or for protecting against such an infection. Excerpt(s): Helicobacter pylori (also designated an H.pylori) is a Gram-negative bacterium which, to date, has been found exclusively on the surface of the mucosa of the stomach in man. In common with most bacteria, H.pylori is sensitive to a medium which is at acid pH but, nevertheless, is able to tolerate acidity in the presence of physiological concentrations of urea (Marshall et al. (1990) Gastroenterol. 99: 697-702). by hydrolysing the urea to form carbon dioxide and ammonia, which are released into the microenvironment of the bacterium, the H.pylori urease enables the bacterium to survive in the acidic environment of the stomach. Recently, studies carried out on animal models have provided data suggesting that the urease is an important factor in the colonization of the gastric mucosa (Eaton et al. (1991) Infect. Immun. 59: 2470-2475). The urease is also suspected of causing injury, either directly or indirectly, to the gastric mucosa. Currently, Helicobacter pylori (H.pylori) is recognized as being the etiological agent of antral gastrites, and appears to be one of the cofactors required for the development of ulcers. Furthermore, it appears that the development of gastric carcinomas may be associated with the presence of H. pylori. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Collection of prokaryotic DNA for two hybrid systems Helicobacter pylori proteinprotein interactions and application thereof Inventor(s): Legrain, Pierre; (Paris, FR), Rain, Jean-Christophe; (Puteaux, FR), Selig, Luc; (Fontenay-sous-Bois, FR) Correspondence: Lerner, David, Littenberg,; Krumholz & Mentlik, Llp; 600 South Avenue West; Westfield; NJ; 07090; US Patent Application Number: 20030017478 Date filed: October 30, 2001 Abstract: The present invention concerns collections of recombinant cell clones derived from a prokaryotic genome, more particularly from Helicobacter pylori genome, useable for two-hybrid systems and methods to produce such collections. The invention further relates to then identification of H. pylori protein-protein interactions and to the application of said collections of recombinant cell clones and said identified proteins interactions to the pharmaceutical and diagnostic field. Excerpt(s): This application is a continuation of International Application No. PCT/IB00/00603, filed Apr. 14, 2000 and published in English. The disclosure of which is incorporated by reference. The present invention concerns new collections of recombinant cell clones derived from a prokaryotic genome, more particularly from Helicobacter pylori genome, usable for two-hybrid systems and methods to produce such collections. The invention further relates to the identification of H. pylori proteinprotein interactions and to the application of said collections of recombinant cell clones and said identified proteins interactions to the pharmaceutical and diagnostic field. Most biological processes involve specific protein-protein interactions. General methodologies to identify interacting proteins or to study these interactions have been developed. The advantages of genetic approaches in drug discovery have recently received increased attention. These advantages include both cost-effectiveness and simplicity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions, test kits and methods for detecting helicobacter pylori Inventor(s): Sachs, George; (Encino, CA), Voland, Petra; (Munich, DE) Correspondence: Gabor L. Szekeres; 8141 E. Kaiser Boulevard; Suite 112; Anaheim; CA; 92808; US Patent Application Number: 20030166027 Date filed: February 21, 2002 Abstract: Four proteins are obtained from H. pylori bacteria each of which has regions which act as antigens specific to H. pylori. The proteins are isolated, purified and designated HP1, HP2, HP3, and HP4 with respective molecular weights of 32 kd, 30 kd, 23 kd and 15 kd. An assay, a method and a kit is developed utilizing a combination of at least three of these protein to detect the presence of antibodies to H. pylori in human sera. The method of detection is quantified and suitable for monitoring the eradication of H. pylori bacteria by drug therapy of human patients infected by these bacteria. Excerpt(s): The invention relates to an antigen composition that can detect the presence of antibodies specific to Helicobacter pylori. The invention also relates to a method for the preparation of the antigens and the composition and a method and kit for detecting

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the presence of the Helicobacter pylori-specific antibodies. The method also is able to detect eradication of the organism, providing novel methodology. Helicobacter pylori (formerly Campylobacter pylori), hereinafter also referred to as H. pylori, was discovered by B. J. Marshall et al. in 1983. It is a gram-negative, spiral shaped, motile bacterium that colonizes the human stomach that more than 50% of the world's adult population in industrial countries and almost 100% in developing countries are infected with. In association with the infection, gastric disorders like chronic gastritis, gastric and duodenal ulcer disease as well as gastric carcinoma occur. The diagnosis of an infection with H. pylori is usually achieved in two ways. Directly (invasive) by endoscopic examination with biopsy, followed by histology and culture of the bacterium and indirectly (non invasive) by testing peripheral blood or serum samples for antibodies against H. pylori or performing a.sup.13C urea breath test (.sup.13C UBT). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

CYCLOHEXANE CARBOCYCLIC ESTER DERIVATIVE AND CYCLODEXTRIN COMPLEX AND COMPOSITION FOR TREATMENT OF HELICOBACTER PYLORI INFECTIONS Inventor(s): KAMODA, OSAMU; (HYOGO, JP), MIZOGUCHI, JUN-ICHI; (HYOGO, JP), SATO, SEIJI; (HYOGO, JP), TAMAKI, EIJI; (HYOGO, JP), YANAGI, TOSHIHARU; (HYOGO, JP) Correspondence: Dike, Bronstein, Roberts And Cushman; Intellectual Property Practice Group; P.O. Box 9169; Edwards And Angell; Boston; MA; 02209; US Patent Application Number: 20020123508 Date filed: August 12, 1998 Abstract: Abstract The present invention relates to a pharmaceutical composition which is appropriate for eradication or extermination of Helicobacter pylon wherein [4-[4-(4methylbenzyloxycarbonyl)phenyl]phenyl trans-4-guanidinomethylcyclohexanecarboxylate or an acid addition salt thereof are compounded and it also relates to a complex consisting them. Excerpt(s): The present invention provides a pharmaceutical composition which is effective for eradication Helicobacter pylori living in human stomach and, accordingly, said invention is utilized in the medical field. The present invention also provides a complex of 4-[4-(4-methylbenzyloxycarbonyl) phenyl]phenyl trans-4guanidinomethylcyc- lohexanecarboxylate or an acid addition salt thereof with.beta.cyclodextrin. Helicobacter pylon is a bacterium which has recently attracted considerable attention in view of its relationship with diseases of digestive organs. It has become an important factor to be taken into consideration especially when diseases, particularly ulcer, of stomach and duodenum is investigated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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dapE gene of helicobacter pylori and dapE- mutant strains of helicobacter pylori Inventor(s): Karita, Mikio; (Hofu-shi, JP), Blaser, Martin J.; (Nashville, TN) Correspondence: Needle & Rosenberg, P.C.; Suite 1000; 999 Peachtree Street; Atlanta; GA; 30309-3915; US Patent Application Number: 20030204068 Date filed: May 27, 2003 Abstract: The invention provides the dapE gene of Helicobacter pylori and H. pylon dapE.sup.- mutants and to methods of using the mutants to express foreign genes and immunize against foreign agents. The dapE gene can consist of the nucleotide sequence defined in SEQ ID NO:1. Nucleic acids of the gidA gene and ORF2 of H. pylori are provided. Examples of these nucleic acids can be found in SEQ ID NO:3 and SEQ ID NO:5, respectively. Having provided these nucleic acids, hybridizing nucleic acids in accord with the description of hybridizing nucleic acids of dapE are also provided. Excerpt(s): The invention pertains to the dapE gene of Helicobacter pylori and H. pylori dapE mutants and to methods of using the mutants to express foreign genes and immunize against foreign agents. Helicobacter pylori are gram negative enteric bacteria that colonize the human gastric mucosa and cause gastritis and peptic ulcer disease (6, 11, 15) and are implicated in malignant neoplasms of the stomach (5, 26, 30, 37). Thus, there exists a need for a method of treating and preventing H. pylori infection. The present invention meets these needs by providing the dapE gene of H. pylori and conditionally lethal mutants of H. pylori which can be used to express foreign proteins and to immunize against H. pylori infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Detection of Helicobacter Pylori Inventor(s): Black, Murdo M.; (Ipswich, GB), Chambers, Paul; (Ipswich, GB), Cowell, David C.; (Wooton-under-Edge, GB), Dunn, Christopher; (Uley, GB), Penault, Caroline; (Derby, GB), Ratcliffe, Norman M.; (Bishopston, GB), Teare, Clive; (Chesterfield, GB) Correspondence: Thompson Coburn, Llp; One Firstar Plaza; Suite 3500; ST Louis; MO; 63101; US Patent Application Number: 20020090667 Date filed: July 12, 2001 Abstract: A method for detecting Helicobacter pylori in a subject's gastroenteral tract involves measuring a change in resistance of an electronic or electrochemical sensor, notably a polypyrrole film, on exposure to gas from the subject's lungs and/or stomach. Depending on the magnitude of the change (if any) a positive or negative result is indicated visually by electronics means. Two sensors are used, one of which receives a sample of gas which has passed through an ammonia-absorbing means to provide a corrected baseline value for the ammonia. The invention also provides apparatus suitable for carrying out the method. Excerpt(s): The present invention relates to a device and method for detecting Helicobacter Pylori in human subjects. It has been known for some time that infection by Helicobacter pylori (H pylori) may increase the risk of a subject suffering from illnesses such as gastritis and duodenitis, and from peptic and duodenal ulcers, Detection of H pylori is therefore desirable to determine whether patients have, or have

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increased risk of having, such illnesses, and to enable appropriate treatment to be given. H pylori produces ammonia and carbon dioxide by the action of a urease on urea in bodily fluids, and various tests have been proposed to detect H pylori by detecting the products of this reaction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Diagnosis and treatment of non-ulcer dyspepsia based on hypothalamic-pituitaryadrenal axis abnormallity Inventor(s): Dinan, Timothy Garard; (Cobh, IE), Keeling, Paul William Napoleon; (Donnybrook, IE) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030170731 Date filed: March 17, 2003 Abstract: An in vitromethod and a kit for the diagnosis of non-ulcer dyspepsia (NUD) in a subject suspected of having NUD, comprises identifying in the subject a dysfunction of corticotropin releasing hormone (CRH) receptors characterised by the subject's response to CRH-induced adrenocorticotropic hormone (ACTH) production by estimating the level of ACTH in a sample of blood or a blood fraction obtained from said subject relative to a control. The method can be used to diagnose NUD in patients who are infected with Helicobacter pylori and those who are free of such infection. Excerpt(s): This invention relates to the diagnosis and therapy of non-ulcer dyspepsia (NUD), for patients who have Helicobacter pylori infection and those who do not. Symptoms of post prandial fullness or bloating, early satiety, excessive flatulence, upper abdominal pain and nausea are commonplace both in primary care and in gastroenterology clinics (Fisher, R. S. and Parkman, H. P. New England J Med (1998), 339, 1376-1381). These symptoms are sometimes attributable to H. pylori infection, however in many cases no organic disease is found. The substantial group of patients who have persistent and occasionally disabling gastric symptoms without organic disease are classified as having functional dyspepsia or NUD (Talley, N. J. et al, Gastroenterology (1992) 102, 1259-68. Non-ulcer dyspepsia is a heterogeneous condition and has been classified according to symptom clusters as dysmotility-like dyspepsia, gastrooesophageal reflux-like dyspepsia, aerophagia, and essential dyspepsia (Talley, N. J. and Philips, S. F., Ann. Inter. Med. (1988) 108, 865-9). NUD is the most common reason for referral to gastroenterology clinics. To date systematic efforts to determine its aetiology have failed. No consistent biochemical or physiological abnormalities have been demonstrated and many gastroenterologists describe this condition as a functional disorder without an organic basis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Diagnostic testing system and method for detecting helicobacter pylori Inventor(s): Chairman, Simon; (Beaconsfield, AU), Marshall, Barry J.; (Dalkeith, AU), McMichael, Donald J.; (South Jordan, UT), Mendis, Aruni H. W.; (Connolly, AU), Peterson, Kristy; (Salt Lake City, UT) Correspondence: Kimberly-clark Worldwide, INC.; 401 North Lake Street; Neenah; WI; 54956 Patent Application Number: 20030082661 Date filed: October 15, 2001 Abstract: A system and method for detecting bacterial infections in the gastrointestinal tract is disclosed. The system includes a carrier having a first well and a second well. A first composition is disposed in the first well and contains urea in powdered form. A second composition is disposed in a second well and contains an indicator. A biopsy of a gastric sample is manipulated with a specimen-handling tool and is first contacted with the first composition and then placed in the second composition. The second composition indicates the presence of an enzyme, which, in turn, indicates the presence of bacteria. Excerpt(s): The present invention relates generally to diagnostic testing for Helicobacter pylori. When a patient is showing symptoms of a gastrointestinal disorder, it is beneficial to rapidly and accurately diagnose the disorder. Diagnostic testing is frequently performed in such situations to determine if a particular medical condition is present in that patient, including, for example, a bacterial infection. Many ailments of the gastrointestinal system in humans are caused at least in part by bacteria. Some examples of such ailments are chronic or atrophic gastritis, gastroenteritis, non-ulcer dyspepsia, esophageal reflux disease, gastric motility disorders, peptic ulcers including gastric and duodenal ulcers, and the like. Bacteria that can cause these types of ailments include those of the genus Campylobacter, and particularly Helicobacter pylori. For example, Helicobacter pylori can cause bacterial infections on the mucosal surface of the gastrointestinal tract, particularly on the surface of the stomach. Helicobacter pylori is a gram-negative spiral organism which produces the enzyme urease. The organism may be found in the upper gastrointestinal tract that includes the esophagus, the stomach, the duodenum, the jejunum and the ileum. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Food or drink product with a disinfection property of helicobacter pylori Inventor(s): Hirata, Haruhisa; (Kanagawa-ken, JP), Kimura, Katsunori; (Saitama-ken, JP), Koga, Yasuhiro; (Kanagawa-ken, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030161820 Date filed: February 14, 2003 Abstract: A food or drink product with a disinfection property of Helicobacter pylori and/or a protection property against infection with H. pylori, comprising as the effective ingredient Lactobacillus gasseri OLL 2716 (FERM BP-6999) with a high disinfection potency of H. pylori.The food or drink product prepared by using the lactic acid bacterium, such as acid milk and the like, is suitable for long-term ingestion as a

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food or drink product with a disinfection property of H. pylori and/or a protection property against infection with H. pylori. Excerpt(s): Technical Field to Which the Invention Belongs The present invention relates to Lactobacillus gasseri (sometimes referred to as L. gasseri hereinafter) with an effect on the disinfection of Helicobacter pylori (sometimes referred to as H. pylori hereinafter) and/or the protection against infection with H. pylori, and a food or drink product containing the lactic acid bacterium. Since the discovery of H. pylori as a bacterium living in stomach in 1983 by Warren et al. [Lancet, I. 1273 (1983)], attention has been focused on the relation with chronic gastritis, gastric ulcer and duodenal ulcer. Recently, it has been evidenced that gastric gland cancer occurs in mongolian gerbil infected with H. pylori, with no administration of any carcinogenic substance [Watanabe et al., Gastroenterology, 115; 642 (1988)] and the relation of H. pylori with gastric cancer has also been suggested as one etiological bacterium thereof. Meanwhile, it is increasingly indicated that the disinfection of H. pylori in H. pylori-positive patients with digestive ulcer can suppress the recurrence of digestive ulcer and therefore, active disinfection therapy of H. pylori has been practiced in European counties and the U.S. As to the method for disinfecting H. pylori, a combination method of antibiotics (.beta.-lactams, aminoglycosides, macrolides, tetracyclines and the like) and antiulcerative agents is general; for example, a combination therapy of three drugs, namely two types of antibiotics (clarithromycin-metronidazole or amoxycilin) and a proton pump inhibitor (PPI) suppressing the secretion of gastric acid, is clinically practiced. However, the most serious drawback of the administration of drugs such as antibiotics for the purpose of the disinfection therapy is the increase of the frequency of the occurrence of drugresistant H. pylori and the occurrence of severe side effects such as diarrhea and allergy and the like, due to the multiple combination of high-dose drugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

HELICOBACTER PYLORI ANTIGEN Inventor(s): CLANCY, ROBERT LLEWELLYN; (NEWCASTLE, AU), CRIPPS, ALLAN WILLIAM; (FARRER, AU), SMITH, CHRISTOPHER JOHN; (DEESIDE, GB) Correspondence: Foley & Lardner; 3000 K Street N W; Suite 500; P O Box 25696; Washington; DC; 200078696 Patent Application Number: 20020071850 Date filed: August 26, 1999 Abstract: A novel protein extracted from H. pylori has a molecular weight of about 5065 kDa and an amino terminal amino acid sequence that has at least 60% identity to a sequence selected from the group consisting of: 1 M V T L I N N E D D Met-Val-ThrLeu-Ile-Asn-Asn-Glu-Asp-Asp; and S V T L I N N E N N E R Ser-Val-Thr-Leu-Ile-AsnAsn-Glu-- Asn-Asn-Glu-Arg- Y Y F E T Tyr-Tyr-phe-Glu-Thr.The protein is capable of inducing anti H. pylori antibodies and can be used as a vaccine against H. pylori. Excerpt(s): The invention relates to a novel antigen of Helicobacter pylori, or antigenic fragments thereof, the use of the antigen or fragments thereof in detecting Helicobacter pylori and kits comprising them as well as vaccines comprising the antigen or fragments thereof and a method for the isolation of the antigen. Gut infections in mammals, and in particular humans, stimulate an immune response in mucous secretions, such as saliva, through activation of the common mucosal immune system. This response often initially parallels an antibody response in serum although is

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generally characterised by the presence of IgA antibodies. However, the immune response in secretions, including saliva, rapidly diminishes following elimination of the antigen (eg bacteria or virus) from the body. Accordingly, the presence of antibody in mucous secretions reflects current, i.e. contemporary, infection. In the case of a microbial infection, for example, antibodies in mucous secretions, herein after referred to as secretious antibodies, reflect the current status of colonisation of the microbe, such as in the gut, and thus, is a useful monitor of contemporary infection. Serum antibody, on the other hand, persists for some time after the microbe is eliminated from the body. A positive serum antibody test, therefore, reflects both past and present exposure to antigen, which is less helpful to the clinician. A positive secretious antibody test, on the other hand, indicates present or contemporary infection by the microbe. The diagnosis of H. pylori infection can be made by microscopy, microbiological culture or urease detection in gastric mucosal biopsies, urea breath test or by the presence of specific antibodies in serum ELISAs. It might be predicted that H. pylori infection, being an infection of the gastric mucosa, would elicit an IgA antibody response in gastric secretion. However it has been discovered that H. pylori-specific antibody in mucous secretion is of the IgG class and not IgA as might have been expected. Little IgA antibody, if any, is detected. Accordingly, AU-A-9067676 is directed to the detection of IgG in mucous secretion specific to H. pylori antigen and thereby provides a means of monitoring current, i.e. contemporary, infection by that microorganism in mammals. The corresponding academic publication is Witt et al, Frontiers in Mucosal Immunology 1, 693-696(1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Helicobacter pylori antigens in blood Inventor(s): Hung, Chung-Ho; (Burlingame, CA), Yi, Ching Sui A.; (Burlingame, CA) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020090660 Date filed: January 10, 2002 Abstract: The present invention relates to the finding and detection of Helicobacter pylori (H. pylori) antigens in blood of infected individuals. The H. pylori antigens are components of H. pylori cells which include, but not limited to DNA, RNA, and fragments of nucleotides, proteins or peptides. H. pylori DNA, RNA, and fragments of nucleotides can be detected by polymerase chain reaction (PCR), ligase chain reaction (LCR), or DNA hybridization methods or other amplification methods. H. pylori proteins or peptides or other antigenic components thereof can be detected by immunoassays or immunoblot using an antibody against H. pylori, preferably an antibody purified by an affinity column. The present invention further provides immunoassay methods, diagnostic kits, and an immunochromatographic assay device for detection of Helicobacter pylori antigens in serum samples. Excerpt(s): The present application is a continuation-in-part (CIP) application which claims the priority of U.S. Provisional patent application Ser. No. 60/170,537, filed on Dec. 14, 1999, and U.S. Utility patent application Ser. No. 09/572,598, filed on May 17, 2000, which are herein incorporated by reference. The present invention relates to the finding of Helicobacter pylori (H. pylori) antigens and antigenic fragments thereof in blood, which includes whole blood, plasma, and serum. The H. pylori antigens found in blood include, but not limited to, H. pylori DNA, RNA, or fragments thereof, or H.

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pylori proteins/peptides or other antigenic components thereof. H. pylori DNA or fragments thereof are detected by polymerase chain reaction (PCR), ligase chain reaction (LCR), DNA hybridization, branched DNA signal amplification assay, or other signal amplification methods. H. pylori RNA thereof are detected by PCR, hybridization or other signal amplification assays. H. pylori proteins or peptides or other antigenic components thereof are detected by immunoassays or immunoblotting using an affinity purified antibody against H. pylori. The present invention also relates to diagnosing H. pylori infection by detecting the H. pylori antigens in blood. Helicobacter pylori (H. pylori) is a gram-negative bacterium which infects the gastric mucosal and is responsible for most peptic ulcer disease (PUD). Until recently, ulcers and other forms of dyspepsia were thought to be related to stress levels or eating habits. Recently, the medical community has confirmed that H. pylori is the causative agent for certain forms of gastric distress, including ulcers and gastric cancer. Eradication of H. pylori promotes healing of ulcer and greatly reduces the incidences of cancer and PuD. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Helicobacter pylori fermentation process Inventor(s): Olivieri, Roberto; (Siena, IT), Rappuoli, Rino; (Quercegrossa, IT), Telford, John Laird; (Monteriggioni, IT) Correspondence: Chiron Corporation; Intellectual Property; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20020192236 Date filed: March 20, 2002 Abstract: The present invention relates to a new method for the growth of Helicobacter pylori and purification of the cytotoxin produced by H. pylori. In particular, H. pylori is cultured in a medium comprising more than 1 gl.sup.-1 of glucose to produce a vacuolating cytotoxin. Excerpt(s): The present invention relates to a new method for the growth of Helicobacter pylori and purification of the cytotoxin produced by H. pylori. In particular the present application relates to a novel medium for the fermentation of H. pylori. H. pylori is a curved gram negative microaerobic bacterium isolated approximately 10 years ago which is associated with type B gastritis in humans. H. pylori colonises the human gastric mucosa and establishes a chronic infection that may result in gastric and duodenal ulcers (Blazer, 1990, Journal of Infectious diseases, 161, 629-633) and can be a risk factor in the development of gastric carcimona (Parsonnet et al, 1991, New England Journal of Medicine, 325, 1227-1131). The discovery of the association between H. pylori and gastric illness has altered the therapeutic approach to such diseases from the treatment of symptoms with anti- acid drugs to the eradication of the bacterial infection using antibiotics (Marshall, 1993, Gastroenterol. Clin. Northam. 22, 183-198). In the long term, the infection and diseases thereby occasioned could be prevented and treated by vaccination. Currently, several factors involved in bacterial adhesion, colonization and virulence have been identified and are the subjects of investigations into their suitability as vaccine components. One of the most interesting factors is the vacuolating cytotoxin (Vac A) that causes massive vacuolisation in several mammalian cell lines (Luenk, 1991, Rev. Infect. Dis. 12 (supplement 8), s683-s689) and ulceration in mice (Telford et al, J. Exp. Med. 179, 1653-1658). The purified cytotoxin is a protein of 87 to 94 KD (Telford et alt op. cit; Cover and Blazer, 1992, J.Biol. Chem. 267, 10570-10575) which may be purified in very small quantities from bacterial culture

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supernatants. In order to gain an understanding of the mechanism of action of Vac A as well as studying its serology, its role in disease and its utility as a vaccinating antigen large quantities of the protein will be required. Such quantities can not be obtained using the current methods for culture of H. pylori and cytotoxin purification. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Helicobacter pylori live vaccine Inventor(s): Gibbs, Carol Patrice; (Augsburg, DE), Gomez-Duarte, Oscar; (Tubingen, DE), Haas, Rainer; (Munchen, DE), Lattemann, Claus Tobias; (Neusaess, DE), Lucas, Bernadette; (Berlin, DE), Maurer, Jochen; (Stadtbergen, DE), Meyer, Thomas F.; (Berlin, DE), Zhengxin, Yan; (Tubingen, DE) Correspondence: Arent Fox Kintner Plotkin & Kahn; 1050 Connecticut Avenue, N.W.; Suite 400; Washington; DC; 20036; US Patent Application Number: 20020161192 Date filed: October 15, 2001 Excerpt(s): The present invention relates to novel recombinant live vaccines, which provide protective immunity against an infection by Helicobacter pylori and a method of screening H. pylori antigens for optimized vaccines. Helicobacter is a gram-negative bacterial pathogen associated with the development of gastritis, pepic ulceration and gastric carcinoma. Several Helicobacter species colonize the stomach, most notably H. pylori, H. heilmanii and H. felis. Although H. pylori is the species most commonly associated with human infection, H. heilmanii and H. felis also have been found to infect humans. High H. pylori infection rates are observed in third world countries, as well as in industrialized countries. Among all the virulence factors described in H. pylori, urease is known to be essential for colonisation of gnobiotic pigs and nude mice. Urease is an enzyme composed of two structural subunits (UreA and UreB). Previous studies have indicated that oral immunization using recombinant UreB plus cholera toxin were able to protect mice from gastric colonisation with H. felis and H. pylori (Michetti et al., Gastroenterology 107 (1994), 1002-1011). By oral administration of recombinant UreB antigens, however, in several cases only an incomplete protection can be obtained. Other H. pylori antigens shown to give partial protection are the 87 kD vacuolar cytotoxin VacA (Cover and Blaser, J. Biol. Chem. 267 (1992), 10570; Marchetti et al., Science 267 (1995), 1655) and the 13 and 58 kD heat shock proteins HspA and HspB (Ferrero et al., Proc. Natl. Acad. Sci. USA 92 (1995), 6499). Attenuated pathogens, e.g. bacteria, such as Salmonella, are known to be efficient live vaccines. The first indications of the efficacy of attenuated Salmonella as good vaccine in humans came from studies using a chemically mutagenized Salmonella typhi Ty21a strain (Germanier and Furer, J. Infect. Dis. 141 (1975), 553-558), tested successfully in adult volunteers (Gilman et al., J. Infect. Dis. 136 (1977), 717-723) and later on in children in a large field trial in Egypt (Whadan et al., J. Infect. Dis. 145 (1982), 292-295). The orally administered Ty21a vaccine was able to protect 96% of the Egyptian children vaccinated during three years of surveillance. Since that time new attenuated Salomonella live vector vaccines have developed (Hone et al., Vaccine 9 (1991), 810-816), in which well defined mutations incorporated into the chromosome gave rise to non-virulent strains able to induce strong immune responses after oral administration (Tacket et al., Vaccine 10 (1992), 443-446 and Tacket et al., Infect. Immun. 60 (1992), 536-541). Other advantages of the live attenuated Salmonella vaccine include its safety, easy administration, long-time protection and no adverse reactions in comparison with the former inactivated wholesale typhoid vaccines (Levine

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et al., Typhoid Fever Vaccines, In; Plotkin S. A., Mortimer E. A. Jr. (eds.) Vaccines. Philadelphia; W B Saunders (1988), 333-361). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Helicobacter pylori membrane proteins Inventor(s): Lissolo, Ling; (Marcy L'Etoile, FR) Correspondence: Paul T Clark; Clark And Elbing Llp; 176 Federal Street; Boston; MA; 02110; US Patent Application Number: 20020151462 Date filed: January 20, 2000 Abstract: The invention relates to proteins of Helicobacter pylori, in a substantially purified forms, that can be obtained from a membrane fraction of H. pylori and of which the molecular weights after electrophoresis on a 10% polyacrylamide gel in the presence of SDS are approximately 54, 50, 32-35, or 30 kDa. Excerpt(s): The object of the present invention is Helicobacter pylori proteins newly obtained in substantially purified form, as well as the pharmaceutical compositions containing them. Helicobacter is a bacterial genus characterized by Gram-negative helical bacteria. Several species colonize the gastrointestinal tract of mammals. There may be mentioned in particular H. pylori, H. heilmanii, H. felis and H. mustelae. Although H. pylori is the species most commonly associated with human infections, in some admittedly rare cases, it has been possible to isolate in man H. heilmanii and H. felis. Helicobacter infects more than 50% of the adult population in developed countries and nearly 100% of that of developing countries, thereby making it one of the predominant infectious agents worldwide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Helicobacter pylori proteins useful for vaccines and diagnostics Inventor(s): Bugnoli, Massimo; (Monteriggioni, IT), Covacci, Antonello; (Siena, IT), Macchia, Giovanni; (Voorburg, NL), Rappuoli, Rino; (Sienna, IT), Telford, John; (Monteriggioni, IT) Correspondence: Alisa A. Harbin, ESQ.; Vice President & Associate Chief Patent Counsel; Chiron Corporation; Intellectual Property - R440, P.O. Box 8097; Emeryville; CA; 94608-8097; US Patent Application Number: 20040048353 Date filed: August 2, 2001 Abstract: This invention provides polypeptides of Helicobacter pylori cytotoxin protein. The invention also provides prophylactic and therapeutic vaccines comprising the polypeptides of Helicobacter pylori cytotoxin protein, and methods for their preparation. Excerpt(s): The present invention relates generally to certain Helicobacter pylori proteins, to the genes which express these proteins, and to the use of these proteins for diagnostic and vaccine applications. Helicobacter pylori is a curved, microaerophilic, gram negative bacterium that has been isolated for the first time in 1982 from stomach

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biopsies of patients with chronic gastritis, Warren et al., Lancet i:1273-75 (1983). Originally named Campylobacter pylori, it has been recognized to be part of a separate genus named Helicobacter, Goodwin et al., Int. J. Syst. Bacteriol. 39:397-405 (1989). The bacterium colonizes the human gastric mucosa, and infection can persist for decades. During the last few years, the presence of the bacterium has been associated with chronic gastritis type B, a condition that may remain asymptomatic in most infected persons but increases considerably the risk of peptic ulcer and gastric adenocarcinoma. The most recent studies strongly suggest that H. pylori infection may be either a cause or a cofactor of type B gastritis, peptic ulcers, and gastric tumors, see e.g., Blaser, Gastroenterology 93:371-83 (1987); Dooley et al., New Engl. J. Med. 321:1562-66 (1989); Parsonnet et al., New Engl. J. Med. 325:1127-31 (1991). H. pylori is believed to be transmitted by the oral route, Thomas et al., Lancet i:340, 1194 (1992), and the risk of infection increases with age, Graham et al., Gastroenterology 100:1495-1501 (1991), and is facilitated by crowding, Drumm et al., New Engl. J. Med. 4322:359-63 (1990); Blaser, Clin. Infect. Dis. 15:386-93 (1992). In developed countries, the presence of antibodies against H. pylori antigens increases from less than 20% to over 50% in people 30 and 60 years old respectively, Jones et al., Med. Microbio. 22:57-62 (1986); Morris et al., N. Z. Med. J. 99:657-59 (1986), while in developing countries over 80% of the population are already infected by the age of 20, Graham et al., Digestive Diseases and Sciences 36:108488 (1991). The nature and the role of the virulence factors of H. pylori are still poorly understood. The factors that have been identified so far include the flagella that are probably necessary to move across the mucus layer, see e.g., Leying et al., Mol. Microbiol. 6:2863-74 (1992); the urease that is necessary to neutralize the acidic environment of the stomach and to allow initial colonization, see e.g., Cussac et al., J. Bacteriol. 174:2466-73 (1992); Perez-Perez et al., J. Infect. Immun. 60:3658-3663 (1992); Austin et al., J. Bacteriol. 174:7470-73 (1992); PCT Publ. No. WO 90/04030; and a high molecular weight cytotoxic protein formed by monomers allegedly having a molecular weight of 87 kDa that causes formation of vacuoles in eukaryotic epithelial cells and is produced by H. pylori strains associated with disease, see e.g., Cover et al., J. Bio. Chem. 267:10570-75 (1992) (referencing a "vacuolating toxin" with a specified 23 amino acid Nterminal sequence); Cover et al., J. Clin. Invest. 90:913-18 (1992); Leunk, Rev. Infect. Dis. 13:5686-89 (1991). Additionally, the following is also known. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Herbal compositions useful as chemopreventive and therapeutic agents and methods of manufacturing same Inventor(s): Lam, Stephen; (Vancouver, CA), Lin, Peizhong; (Beijing, CN), Tai, Joseph; (Vancouver, CA), Tze, John Wah; (Vancouver, CA) Correspondence: Michael L. Goldman; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603; US Patent Application Number: 20030099725 Date filed: February 26, 2001 Abstract: Compositions derived from traditional Chinese herbal medicines, medicinal plants and extracts thereof, are provided for the prevention and treatment of cancers especially cancer of the lung, esophagus, stomach, oral cavity and prostate as well as for treating Helicobacter pylori infection. The compositions of the invention are obtained through specific techniques and have demonstrated efficacy for chemoprevention of cancers of the lung, esophagus, stomach, and the oral cavity as well as exhibiting in vitro

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activity against prostate cancer and leukemic cell lines. The compositions are useful as adjuncts to conventional surgery or radiotherapy treatments in patients with esophageal cancer. The compositions are effective as a treatment for H. pylori infection. Currently, there is no effective chemopreventive agent for these cancers. The current invention addresses a special need in cancer control. Preferred compositions of the invention contain the herbal ingredients Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus Turcz, and Dioscorea bulbifera. Excerpt(s): The present invention relates to compositions comprising herbs derived from traditional Chinese medicine and their use as chemopreventive and therapeutic agents. Processes for manufacturing and formulating the compositions are also described. For the past twenty-five years there has been significant progress in the field of cancer research; however, in spite of these positive results, the mortality rate for the most common cancers still remains high. Indeed, the goal of the National Cancer Institute of a fifty percent reduction in overall cancer mortality by the year 2000 has not been met. The term "cancer" is a general one referring to more than 100 forms of the disease which may manifest itself in almost every tissue type of the body. Of the myriad forms of cancer, lung cancer is the most common cause of death worldwide, followed by stomach cancer. Other common forms of cancer include cancers of the colon, rectum, breast, prostate, mouth and esophagus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunological combinations for prophylaxis and therapy of helicobacter pylori infection Inventor(s): Guy, Bruno; (Lyon, FR), Haensler, Jean; (Pollionnay, FR) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20040033240 Date filed: June 9, 2003 Abstract: The invention relates to multivalent compositions for preventing or treating Helicobacter infections. Multivalent Helicobacter component compositions useful in prophylaxis comprises at least two, preferably three components, that are selected from AlpA, catalase, urcase, 525 protease and 76K proteins. Multivalent compositions useful in therapy include in particular 76K+caatalase+525 protease, urease+76K+catalase+525 protease, AlpA+76K+catalase+525 protease, AlpA+76K and AlpA+catalase. Excerpt(s): This invention relates to the fields of medicine, immunology and vaccinology. In particular, the invention relates to novel antigenic compositions and their use in immunological compositions or vaccines for the treatment and prevention of infection by Helicobacter pylori. The invention relates to multivalent compositions for preventing or treating Helicobacter infections. Multivalent Helicobacter component compositions useful in prophylaxis comprise at least two, preferably three components, that are selected from AlpA, catalase, urease, 525 protease and 76K proteins. Multivalent compositions useful in therapy includes in particular 76K+catalase+525 protease, urease+76K+catalase+525 protease, AlpA+76K+catalase+525 protease, AlpA+76K and AlpA+catalase. Helicobacter pylori (H. pylori) infection is associated with significant gastroduodenal disorders, including gastritis, ulcers and gastroesophageal cancer (P. Correa 1995 Am. J. Surg. Pathol. 19 (suppl. 1) s37-s43; B. J. Marshall et al. 1984 Lancet 1: 1311-1315; J. Parsonnet 1995 Aliment Pharmacol. Ther. 9 (Suppl 2) 45-51). Various H.

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pylori antigens have been tested in animal models for their ability to elicit a protective immunological response against infection, using a variety of formulations and various routes of administration. Various H. pylori proteins have been characterized or isolated so far. Antigens of H. pylori described to date include urease, which is composed of two subunits A and B of 30 and 67 kDa respectively (Hu & Mobley, Infect. Immun. (1990) 58: 992; Dunn et al., J. Biol. Chem. (1990) 265: 9464; Evans et al., Microbial Pathogenesis (1991) 10: 15; Labigne. et al., J. Bact. (1989) 173: 1920); the vacuole cytotoxin of 87 kDa (VacA) (Cover & Blaser, J. Biol. Chem (1992) 267: 10570; Phadnis et al., Infect. Immun. (1994) 62: 1557; WO 93/18150); and immunodominant antigen of 128 kDa associated with the cytotoxin (CagA, also called TagA) (WO 93/18150; U.S. Pat. No. 5,403,924); heat shock proteins HspA and HspB of 13 and 58 kDa respectively (Suerbvaum et al., Mol. Microbiol. (1994) 14: 959; WO 93/18150; a catalase of 54 kDa (Hazell et al., J. Gen. Microbiol. (1991) 137 : 57; F. J. Radcliff et al. 1997 Infect. Immun. 65: 4668-4674); a fibrillar haemaglutinin (HpaA) of 20 kDa; a histidine-rich protein of 15 kDa (JHpn) (Gilbert et al., Infect. Immun. (1995) 63 : 2682); an outer membrane protein of 30 kDa (Bolin et al., J. Clin. Microbiol. (1995) 33: 381); a membrane-associated lipoprotein of 20 kDa (Kostrcynska et al., J. Bact. (1994) 176: 5938) as well as a family of porins HopA, HopB, HopC and HopD, of molecular weight between 48 and 67 kDa (Exner et al., Infect. Immun. (1995) 63: 1567). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for treating water for use in improving the intestinal flora of livestock and poultry Inventor(s): Johnson, Troy T.; (Portland, OR), Lorenz, John d?apos;Arc II; (New York, NY), Orolin, John J.; (West Linn, OR), Schorzman, Scott A.; (Kenmore, WA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20020168418 Date filed: February 6, 2002 Abstract: A water treatment system for treating water for use in improving the intestinal flora of livestock and poultry. The treated water for livestock and poultry use provides water with increased dissolved oxygen such that when the treated water is ingested, the livestock and poultry have increased lactic acid producing bacteria and decreased coliforms in the intestine. Increasing the molecular oxygen content in the intestine through providing the birds with treated water containing higher an increased level of dissolved oxygen alters the balance of flora in favor of the beneficial bacteria, thereby improving bird health and performance. By reducing the numbers of strict anaerobes in the gut of the growing bird, the risk of infectious disease, and hence morbidity and mortality are reduced. This allows the beneficial bacteria to proliferate thereby enhancing the digestion and absorption of available nutrients to the bird. The net effect of encouraging the beneficial bacteria, such as Lactobacilli, and suppressing the pathogenic bacteria such as Salmonella, Shigella, Staphylococcus, Escherichia coli, Clostridium and Helicobacter pylori, is greater body weight and improved feed efficiency and healthier animals with fewer antibiotics. The system includes a water treatment filter, a flow meter that coordinates with a flow switch and an electrocatalytic cell coupled to a holding chamber that is attached to an outlet of the cell. Excerpt(s): This invention relates generally to a water treatment system and more particularly, to a method and apparatus for treating water for livestock and poultry use

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such that the livestock and poultry have increased lactic acid producing bacteria and decreased coliforms in the intestine when ingesting the treated water. The need for high quality water in livestock and poultry production is becoming increasingly essential. This is primarily due to the overall reduction in water quality and the trend towards larger and denser livestock and poultry populations. Water quality, whether it be ground or surface water, has been deteriorating over many years for reasons that range from animal waste and agricultural chemical runoff to lowered ground water tables. Occurrences of contamination from nitrates, bacteria, chemicals, iron, hydrogen sulfide, etc., have become more and more prevalent. Poor water quality has resulted in higher disease and morbidity rate in livestock and poultry, which has increased the need for antibiotic use. Drinking water quality is an important factor for livestock and poultry health. Elevated concentrations of minerals, bacteria or toxic constituents in the water can have a detrimental effect on normal physiological processes in the body, thus causing inferior development, such as weight gain and growth. High concentrations of minerals can also restrict water flow to the birds by clogging the feeder lines. This can cause flooding of the drinkers and wet litter, which, in turn, can lead to disease and leg problems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for detecting helicobacter pylori and heilmanii in fecal and salivary specimen and biopsy material Inventor(s): Armbruster, Franz Paul; (Bensheim, DE), Crevar, Katarina; (Babenhausen, DE), Ruppert, Jana; (Lautertal, DE) Correspondence: Jesse A Hirshman; Kirkpatrick & Lockhart; Henry W Oliver Building; 535 Smithfield Street; Pittsburgh; PA; 15222-2312; US Patent Application Number: 20030148411 Date filed: January 22, 2003 Abstract: The invention relates to a method for detecting pathogenic organisms, in particular Helicobacter pylori and H.heilmanii, in fecal, salivary and secretory samples by means of a double-antibody sandwich assay. The inventive method is characterized by dissolving or dispersing the sample having the pathogen antigen in a buffer solution and contacting the buffer solution with a solid phase to which at least two primary antibodies are bound, one of which specifically binds to the pathogenic antigen and the other to human immunoglobulin A; washing the solid phase of non-specifically bound proteins and contacting the solid phase with a secondary antibody which specifically binds to pathogenic antigen, and determining the quantity of specifically bound secondary antibodies. Excerpt(s): The invention relates to a method of detecting Helicobacter antigens in fecal and salivary samples or biopsy materials. The human gastric mucosa is often colonised by bacteria of the genera Helicobacter pylon and heilmanii or Campylobacter. Infection with these bacteria probably occurs from person to person, but drinking water and foodstuffs are not excluded as sources of infection. The strain Helicobacter heilmanii is passed on by domestic animals such as cats, dogs, rabbits, and also by farm animals such as cows. For this reason persons involved in farming and animal care are particular subjected to infection. In Germany, about 10% of school children, 30% of people in their thirties and about 75% of senior citizens are infected with H.pylori. World-wide, ca. 50% of people carry this infection. 80% of incidents of gastritis, 95% of duodenal ulcers and 70% of ventricular ulcers are caused by H.pylori. Further, chronic H.pylori gastritis

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(Type B gastritis) is considered as a precursor for gastro-adeno carcinoma and gastric lymphoma. According to the WHO, H.pylori is a carcinogen of the highest cancer risk class. Only a small proportion of H.pylori infected people develop symptoms. Many live, despite a gastritis, without noticeable complaints or they attribute the rather nonspecific symptoms to other causes. An acute H.pylori gastritis manifests itself through indeterminate pains in the upper and middle stomach, feelings of pressure and fullness, acid eructation, heartburn and through nausea and retching. In practically all patients having a Type B gastritis, an H.pylori infection can be found. Despite the commonly massive immune reaction the infection becomes chronic with these patients. Whether an ulcer develops depends upon the immune system of the patient and upon the aggressiveness of the bacteria or the kind of bacteria type. Spontaneous recoveries are rare. As a rule, a H.pylori infection, if not treated, persists for the whole life. An H.pylori infection can be diagnosed by means of culturing the pathogen from an antrum or corpus biopsy or by means of histological testing of the tissue. Further diagnostic methods are the CLO test (test for Campylobacter-Like Organisms) or the urease urea test, the.sup.13C-Isotope breath test, the detection of antibodies against H.pyloriin the serum, the PCR detection of Helicobacter DNA in a gastric fluid or fecal sample and the detection of H.pylori antigens in a fecal sample. U.S. Pat. No. 5,716,791 (Larka et al.) and EP 0 806 667 (Meridian Diagnostics Inc.) describe an immunoassay for H.pylori antigens in the stool. The assay is based on two affinity purified polyclonal antibodies against H.pylori antigen. Further there is available from Connex GmbH, Martinsried, Germany, an instant test which is based on a lateral flow chromatography of gold-marked monoclonal antibodies against H.pylori stool antigens. These so-called HpSA tests (Helicobacter pylori Stool Antigen) have provided in various clinical studies a good agreement with cases diagnosed by other means, but a high percentage of the tests do not lead to an unambiguous result. The HpSA test is, moreover, unsuitable for monitoring an eradication treatment, since it only functions with abundant quantities of H.pylori antigen in the stool. The further diagnostic methods are in part very complicated, stressful for the patient, or too expensive for routine testing. The serological methods are disadvantageous in that they do not permit a course of treatment to be monitored, since the antibody titre remains high even months after an eradication of the bacteria. A monitoring of the course of treatment is, however, essential since resistance may be present against the antibiotics, such as Clarithromycin, Metronidazole, Amoxicillin, Omeprazol or Proton Pump Inhibitor, used. Treatment of the infections by means of antibiotics and alternative natural remedies thus requires a simple, reliable and sensitive test method for H.pylori. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the diagnosis of Helicobacter pylori infection, and a diagnostic kit for performing the method Inventor(s): Aygen, Sitke; (Cologne, DE) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030032081 Date filed: August 8, 2002 Abstract: The method for the diagnosis of Helicobacter pylori infection by the oral administration of defined amounts of.sup.13C-labeled urea and examination for.sup.13C content of blood samples removed at a defined time is effected bya)

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removing from 0.1 to 0.6 ml of capillary blood from the finger or ear lob of a patient or venous blood of a patient, in both cases with an empty stomach before the beginning of the test;b) administering an exact amount of from 10 to 50 mg of.sup.13C-urea in aqueous solution with a pH value of 2 to 4 to the patient;c) again removing capillary or venous blood exactly after 10 to 15 min from the administration; andd) determining the.sup.13C content of the blood samples by isotope ratio mass spectrometry (IRMS), and deducing the presence of Helicobacter pylori from the increase of the.sup.13C values. Excerpt(s): The present invention relates to a method for the diagnosis of Helicobacter pylori infection by the oral administration of defined amounts of.sup.13C-labeled urea and examination for.sup.13C content of blood samples removed at a defined time. The previously usual and mostly performed method for the diagnosis of Helicobacter pylori infection is the.sup.13C-urea respiration test. This method has been described in detail in EP-A-0 253 927. This test has the disadvantage, that it cannot be applied for children below 3 years and adults suffering from breathinsufficiency like asthma. Rex MoultonBarrett et al., The American Journal of Gastroenterology, Vol. 88, 1993, pages 369 to 374, describe a method in which.sup.13C-labeled hydrogencarbonate is determined in the serum upon oral administration of.sup.13C-labeled urea. In this test, 5 mg/kg of.sup.13C-labeled urea was administered to the patient, and blood samples of 3 ml each were taken and examined after 15, 30, 60, 90, 120 and 180 min. This method has been further examined and described by Mark J. Kim et al. in Gastroenterology 1997, 113: 3137, W. D. Chey et al. in The American Journal of Gastroenterology, Vol. 94, 1999, pages 1522 to 1524, Alan F. Cuttler et al. in The American Journal of Gastroenterology, Vol. 94, 1999, pages 959 to 961, and has resulted in the introduction of a test by the company Metabolic Solutions Inc., Nashua, N.H. In this test, without determination of the zero value and upon administration of a high-fat test meal "Ensure", 125 mg of.sup.13C-urea is administered, and the.sup.13C content of 3 ml of blood is determined after 30 min. However, due to the low accuracy and precision and due to the very high price of the necessary amount of.sup.13C-urea and the relatively high test quantity of blood, this test was not successful economically, so that the respiration test remained the mostly used test method despite of all its disadvantages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the production of the egg containing anti-pathogenic bacteria specific antbodies(igy) and the yogurt and ice cream containing the igy Inventor(s): Baek, Ban-Suk; (Gyeonggi-do, KR), Jung, Kwnag-Yong; (Daejeon, KR), Lee, Nam-Hyung; (Seoul, KR), Ryu, Jung-Soo; (Daejeon, KR), Sunwoo, Sun-Young; (Seoul, KR) Correspondence: Fleshner & Kim; PO Box 221200; Chantilly; VA; 20153-1200; US Patent Application Number: 20030185856 Date filed: November 27, 2002 Excerpt(s): The present invention provides the method for the production of the egg containing anti-pathogenic bacteria specific antibodies (IgY) preventing gastritis, diarrhea, and food poisoning by immunizing young hens with antigen proteins of E. coli causing enteritis, Helicobacter pylori causing gastritis, and Salmonella enteritidis and Salmonella typhimurium, causing food poisoning, simultaneously, the composition containing the protein powders of the specific antibodies described above, mixed in the appropriate ratio, which produced by immunization with the four antigens separately,

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and the foodstuff processed with milk, such as the yogurt and ice cream, containing the anti-pathogenic bacteria specific antibodies (IgY). Additionally, as the method for isolating the protein powders of the specific antibodies, the method for separating protein and phospholipid, particularly, proceeded in a process of diluting egg yolk with distilled water in 1:1 ratio, adding the appropriate amount of ammonium sulfate which enable water-soluble protein and phospholipid to separate, and the method for separating the pigment of egg-yolk and water-soluble protein, proceeded in a process of diluting those separated solution with distilled water, sitting in the certain temperature to precipitate and purify the proteins. The prior art related to patent of E.1coli is summarized as following. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treatment of bacterial infections with once or twice-weekly administered rifalazil Inventor(s): Montgomery, Alan B.; (Bellevue, WA), Porubek, David J.; (Seattle, WA), Rose, Lynn M.; (Seattle, WA) Correspondence: Hana Verny; Peters, Verny, Jones & Schmitt Llp; Suite 6; 385 Sherman Avenue; Palo Alto; CA; 94306; US Patent Application Number: 20030203903 Date filed: September 14, 2002 Abstract: A method for treatment of bacterial infections with rifalazil administered onceweekly, or twice-weekly. A method for treatment of tuberculosis caused by Mycobacterium tuberculosis, infections caused by Mycobacterium avium complex, infections caused by Chlamydia pneumoniae and infections caused by Helicobacter pylori by administering to a patient suffering from the bacterial infection 1-100 mg of rifalazil once or twice a week. In this dose regimen, the treatment is fast, efficacious and eliminates undesirable secondary symptoms observed with daily doses of 1-50 mg of rifalazil. Excerpt(s): This application is based on and claims priority of Provisional Application Serial No. 60/112,921 filed on Dec. 18, 1998. The current invention concerns a method for treatment of bacterial infections with rifalazil administered once-weekly or twiceweekly. In particular, the invention concerns a method for treatment of tuberculosis caused by Mycobacterium tuberculosis, infections caused by Mycobacterium avium complex, infections caused by Chlamydia pneumoniae and infections caused by Helicobacter pylori by administering to a patient suffering from the bacterial infection rifalazil once or twice a week. In this dose regimen, the treatment is fast, efficacious and eliminates undesirable secondary symptoms observed with daily doses of 1-50 mg of rifalazil. Bacterial infection caused by mycobacterium species and similar infections caused by Chlamydia pneumoniae or H. pylori cause serious health problems in the United States and worldwide. For example, tuberculosis, caused by Mycobacterium tuberculosis is one of the most serious infectious diseases outside of developed countries, with over one billion people infected worldwide. The worldwide infection rate results in eight million active tuberculosis cases annually and over two million deaths per year. In the United States, 26,000 new cases of active tuberculosis were reported in 1994. The number of active cases in the United States is high because of the increase in patients with AIDS and the increase in immigration from developing countries. Moreover, there is reported an increase in multidrug resistance tuberculosis and disseminated Mycobacterium avium complex infections.

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

Method of screening ptp.cedilla. activitiy promoter or inhibitor Inventor(s): Fujikawa, Akihiro; (Aichi, JP), Noda, Masaharu; (Aichi, JP) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030186284 Date filed: January 24, 2003 Abstract: An object of the present invention is to provide a remedy for dysfunction of central monoamine pathway, a method for screening a PTP.zeta. inhibitor or activator, which is useful as a remedy for gastric ulcer caused by Helicobacter pylori or pleiotrophin which is a heparin-binding secretory protein, and a non-human model animal being hyposensitive to a stimulant drug, VacA which is a toxin of Helicobacter pylori, or pleiotrophin by utilizing the physiological function of PTP.zeta. After administering a subject material to PTP.zeta. knockout mice and wild-type mice, PTP.zeta. activity in the PTP.zeta. knockout mice and the wild-type mice is compared and evaluated to screen a PTP.zeta. inhibitor or activator. Examples of the comparison and the evaluation of the PTP.zeta. activity include the comparison and the evaluation of the function of central monoamine pathway such as changes in the level of central monoamine metabolism, sensitivity to a stimulant drug, the presence of dysfunction of mesolimbic dopamine pathway, level of acclimation to new circumstances, or stressresponsiveness, and the comparison and the evaluation of the level of binding to VacA, a toxin of Helicobacter pylori, or pleiotrophin. Excerpt(s): The present invention relates to a remedy for dysfunction of central monoamine pathway with the use of a non-human animal such as a mouse or the like which is generated by a homologous recombination technique for genes and is deficient in its receptor-type protein tyrosine phosphatase (PTP.zeta./RPTP.beta.) gene, a screening of a remedy for gastric ulcer caused by Helicobacter pylori or the like, a nonhuman model animal being hyposensitive to a central stimulant drug (an addictive drug) and a non-human model animal being hyposensitive to VacA, a toxin of Helicobacter pylori, or the like. When a cell receives a stimulus from outside, its intracellular signaling pathway is activated to induce proliferation, differentiation, apoptosis and the like of the cell. Tyrosine phosphorylation of intracellular proteins acts an extremely important role in various phases of the signaling pathway, and the state of tyrosine phosphorylation of each protein is always regulated by dynamic equilibrium of delicate balance of two families of enzymes, tyrosine kinase (PTK) and tyrosine phosphatase (PTP). It is known that this tyrosine phosphorylation of proteins is involved in controlling the efficiency of neural circuit formation and neurotransmission in brains (SEITAI NO KAGAKU Vol. 48, No. 6, 534-538, (1997); PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1136-1143 (1998)), and is important for the formation and the maintenance of the functions in an immune system and other organs (PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1131-1135 (1998)). On the other hand, it is reported that the abnormal tyrosine phosphorylation of proteins is involved in defects in neural circuit formation, disturbance of memory and learning, abnormal apoptosis, tumorigenesis or the like (PROTEIN, NUCLEIC ACID AND ENZYME Vol. 43, No. 8, 1186-1192 (1998)). To date, more than 80 kinds of PTP have been identified, and it is presumed that the number of genes of PTP in human would reach to 500. Similar to PTK, PTP is classified into two types: a receptor type and a non-

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receptor type. A receptor-type PTP has two or one enzymic domain intracellularly, and is classified into several groups according to the characteristics of its extracellular domain. PTP.zeta., which has a carbonic anhydrase domain in N-terminal, has been identified as a receptor-type tyrosine phosphatase specific to the central nervous system. The inventors of the present invention have reported that PTP.zeta. is a receptor of growth factors including pleiotrophin and midkine (J. Biol. Chem. 271, 21446-21452, 1996; J. Cell Biol. 142, 203-216, 1998; J. Biol. Chem. 274, 12471-12479, 1999). In addition, PTP.zeta. is known to interact with cell adhesion molecules which belong to the immunogloblin super family, such as N-CAM, and is thought to be responsible for important functions in differentiation, migration and neurotransmission of neurons. The present inventors have already generated a PTP.zeta. gene-deficient mouse and reported that PTP.zeta. has expressed in both neurons and astrocytes (Neuroscience Letters 274, 135-138, 1998). The PTP.zeta. gene-deficient mouse has grown and propagated normally, and no major morphologic abnormality has been identified. However, the physiological role of PTP.zeta. has been hardly elucidated so far. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for treating or preventing bacterial infection Inventor(s): Muramatsu, Mitsumi; (Tokushirma-shi, JP), Ni, Cheng; (Zhengjiang, CN), Wang, Ming-Wei; (San Deigo, CA), Xie, Jianshu; (Shanghai, CN), Zhu, Dexu; (Nanjing, CN) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20030125384 Date filed: October 10, 2001 Abstract: The invention relates to compositions and methods for treating or preventing disease or disorders caused by or associated with certain bacterial infection, especially Escherichia coli (E. coli) or Helicobacter pylori (H. pylori) infection. Excerpt(s): The invention relates to compositions and methods for treating or preventing diseases or disorders caused by or associated with certain bacterial infection, especially Escherichia coli (E. coli) or Helicobacter pylori (H. pylori) infection. Since the discovery of penicillin in 1929, we now have over 150 antibiotics. They belong to several classes of antibiotics and have different mechanism of actions (Lyon and Skurray, Microbiol. Rev., 51:88-134, (1987)). In general, these compounds are made by living organisms that inhibit growth and proliferation of bacteria. For example, vancomycin and.beta.-lactam can block cell wall synthesis (Chopra et al., Antimicrob. Agents Chemother., 41:497-503, (1997); and Nicolaou et al., Scientific American, 48-52 May (2001)). Erythromycin and tetracycline can disrupt protein synthesis. Sulfonamide interferes with folic acid metabolism, rifampin can block RNA synthesis, and quinolone inhibits DNA replication. To combat the bacterial resistance, new approaches of treating bacteria infections are under research and development. These new approaches involve giving new life to existing antibiotics such as molecular alteration. Recently, a new class of antibiotics "self-assembling peptide nanotubes" generated interests (Associated Press New, Jul. 25, 2001). This compound uses rings of microscopic amino acids that form tubes to push through the surface of bacterium. There are also many new developments in the genomic areas. They entail interfering with bacterial RNA (rRNA) and messenger RNA (mRNA). A new technique called in vivo expression technology (IVET) that can tag bacteria genes is also under research. In addition, a promising approach is the

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antisense therapy for treating bacterial infections (Jasny et al., Science, 286:443-491, (1999)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for monitoring treatment of helicobacter infection and for predicting the likelihood of successful eradication Inventor(s): Borody, Thomas Julius; (New South Wales, AU), Clancy, Robert Llewellyn; (New South Wales, AU), Pang, Gerarld; (New South Wales, AU), Ren, Zhigang; (New South Wales, AU) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20040038329 Date filed: July 31, 2003 Abstract: The present invention relates to methods for monitoring treatment of Helicobacter infection and in particular to methods for monitoring eradication of Helicobacter pylori infection using immunoglobulin G2 (IgG2). The invention also relates to methods for predicting the likelihood of successful eradication of Helicobacter infection in a subject to be treated or being treated for the infection and in particular, to methods for predicting the likelihood of successful eradication including determining the levels of interleukin, interferon-.gamma. and IgG in the subject to be, or being treated. Excerpt(s): Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. Helicobacter pylori infection is now recognised as an essential pre-requisite for the development of gastric cancer. About 30% of the population become infected with this bacterium and commonly present with chronic gastritis. This may be complicated by gastric or duodenal ulceration, or may present as non-ulcer dyspepsia A sizeable number of carriers are asymptomatic. However, in a small number of patients with H. pylori, their condition evolves through stages (including epithelial cell metaplasia and dysplasia) into neoplasia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of inhibiting helicobacter pylori Inventor(s): Cussac, Valerie; (Paris, FR), De Reuse, Hilde; (Paris, FR), Labigne, Agnes; (Bures-sur-Yvette, FR), Skouloubris, Stephane; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20020102269 Date filed: December 22, 2000 Abstract: This invention relates to methods of screening molecules capable of inhibiting the survival of Helicobacter pylori in vivo by specifically inhibiting the activity of UreI, to the molecules identified by these methods, and to the use of these molecules to treat or prevent H. pylori infection.

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Excerpt(s): This invention relates to methods of screening molecules capable of inhibiting the survival of Helicobacter, particularly Helicobacter pylori, in vivo by specifically, inhibiting the activity of UreI, to the molecules identified by these methods, and to the use of these molecules to treat or prevent Helicobacter infection. Helicobacter priori is a microaerophilic Gram-negative bacterium, which colonizes the gastric mucosa of humans (10). H. pylori is associated with gastritis and peptic ulcer disease and has been shown to increase the risk of gastric cancers. Urease is a major virulence factor of H. pylori. It is involved in neutralizing the acidic microenvironment of the bacterium and also plays a role in H. pylori metabolism (11, 26). The distances separating UreI from ureE (one base pair, bp) and ureE from ureF ( 11 bp) suggest that ureI-ureE-ureF constitute an operon. Cotranscription of ureI and ureE has been demonstrated by northern blot analysis (1). An H. pylori N6 mutant with a ureI gene disrupted by a MiniTn3-Km transposon was previously described by Ferrero et al. (1994) (13). This strain (N6-ureI::TnKm-8) presented a urease negative phenotype, so it was concluded that ureI was an accessory gene required for full urease activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

New use of compounds as antibacterial agents Inventor(s): Eek, Arne; (Trosa, SE), Raud, Johan; (Bromma, SE) Correspondence: Fitch Even Tabin And Flannery; 120 South LA Salle Street; Suite 1600; Chicago; IL; 60603-3406; US Patent Application Number: 20040048917 Date filed: May 1, 2003 Abstract: 1The present invention discloses a new use of NO-releasing NSAIDs, especially NO-releasing NSAIDs of the formula I, or a pharmaceutically acceptable salt or enantiomer thereof, for the manufacture of a medicament for the treatment of bacterial infections, especially caused or mediated by Helicobacter pylori.Disclosed is also the new use of a NO-releasing NSAID in combination with an acid susceptible proton pump inhibitor for the treatment of bacterial infections. Excerpt(s): The present invention is directed to a new use of nitric oxide-releasing Non Steriodal Antiinflammatory Drugs (NO-releasing NSAIDs). More particularly the invention is directed to the use of NO-releasing NSAIDs for the manufacture of a medicament for the treatment of bacterial infections, particularly caused or mediated by Helicobacter pylori as well as a combination with acid susceptible proton pump inhibitors for the treatment of bacterial infections. NSAIDs, are among the most commonly prescribed and used drugs worldwide. Despite the therapeutic benefits of NSAIDs, their use is limited. The use of NSAIDs may lead to gastric mucosal damage due to inhibited production of prostaglandins which increases the risk of gastrointestinal side-effects. A recent proposal for reducing the side-effects associated with NSAIDs treatment is to use nitric oxide-releasing NSAID derivatives (NO-releasing NSAIDs) (del Soldato P et al., NO-releasing NSAID:s, A novel class of safer and effective antiinflammatory agents; Inflammopharmacology, 1996; 4; 181-188). NO-releasing NSAIDs reduce the gastrointestinal side-effects but still have the pharmacological activity characteristic of the frequently used NSAIDs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use Inventor(s): Bandarage, Ramani R.; (Newton, MA), Bandarage, Upul K.; (Newton, MA), Fang, Xinqin; (Lexington, MA), Garvey, David S.; (Dover, MA), Letts, L. Gordon; (Dover, MA), Schroeder, Joseph D.; (Dedham, MA), Tam, Sang William; (Dover, MA) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20030220228 Date filed: June 18, 2003 Abstract: The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endotheliumderived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B.sub.4 (LTB.sub.4) receptor antagonists, leukotriene A.sub.4 (LTA.sub.4) hydrolase inhibitors, 5-HT agonists, 3hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H.sub.2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or nonsedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2. Excerpt(s): This application is a divisional of U.S. application No. 09/741,816, filed Dec. 22, 2000, now allowed, which claims priority to U.S. Provisional Application No. 60/171,623 filed Dec. 23, 1999 and U.S. Provisional Application No. 60/226,085 filed Aug. 18, 2000. Nonsteroidal anti-inflammatory compounds (NSAIDs) are widely used for the treatment of pain, inflammation, and acute and chronic inflammatory disorders such as osteoarthritis and rheumatoid arthritis. These compounds inhibit the activity of the enzyme cyclooxygenase (COX), also known as prostaglandin G/H synthase, which is the enzyme that converts arachidonic acid into prostanoids. The NSAIDs also inhibit the production of other prostaglandins, especially prostaglandin G.sub.2, prostaglandin H.sub.2 and prostaglandin E.sub.2, thereby reducing the prostaglandin-induced pain and swelling associated with the inflammation process. The chronic use of NSAIDs has been associated with adverse effects, such as gastrointestinal ulceration and renal toxicity. The undesirable side effects are also due to the inhibition of prostaglandin in the affected organ. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nitrosated proton pump inhibitors, compositions and methods of use Inventor(s): Fang, Xinqin; (Lexington, MA), Garvey, David S.; (Dover, MA), Letts, L. Gordon; (Dover, MA) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20040024014 Date filed: August 1, 2003 Abstract: The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated proton pump inhibitor compound, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections. Excerpt(s): This application claims priority to U.S. application Ser. No. 60/399,715 filed Aug. 1, 2002. The proton pump, located in the apical membrane of the parietal cell, is responsible for the secretion of acid in the stomach when it is stimulated by the enzyme adenosine triphosphate (H.sup.+, K.sup.+)-ATPase. Proton pump inhibitors are a class of anti-secretory compounds used in the management of gastrointestinal disorders. They suppress gastric acid secretion by the specific inhibition of the (H.sup.+, K.sup.+)ATPase enzyme system at the secretory surface of the gastric parietal cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Optically active pyrrolopyridazine derivatives Inventor(s): Fujiwara, Hiroshi; (Ube-shi, JP), Hagihara, Masahiko; (Ube-shi, JP), Ito, Keiichi; (Kawaguchi-shi, JP), Matsunobu, Keiji; (Ube-shi, JP), Shibakawa, Nobuhiko; (Ube-shi, JP) Correspondence: Frishauf, Holtz, Goodman &; Langer & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20020156079 Date filed: December 12, 2001 Abstract: An optically active pyrrolopyridazine compound of the formula (I) or a pharmaceutically acceptable salt thereof: 1wherein R.sup.1 is alkyl; R.sup.2 and R.sup.3 are each independently alkyl; R.sup.4 is optionally substituted aryl; and A is imino,

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oxygen or sulfur. The pyrrolopyridazine compound or pharmaceutically acceptable salts thereof of the present invention exhibit excellent gastric acid secretory inhibition activity and gastric mucous membrane protection activity, as well as excellent antibacterial activity against Helicobacter pylori. They are useful medicines and are particularly useful for treating or preventing ulcerative diseases. Excerpt(s): This application is a continuation application of International Application PCT/JP00/03895 filed Jun. 15, 2000, which was not published in English under PCT Article 21(2). This invention relates to optically active pyrrolopyridazine derivatives of formula (I) or pharmaceutically acceptable salts thereof. This invention further relates to pharmaceutical compositions comprising an optically active pyrrolopyridazine derivative of formula (I) or a pharmaceutically acceptable salt thereof (preferably compositions for prevention or treatment of an ulcerative disease) as an active ingredient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Piperidinylaminomethyl trifluoromethyl cyclic ether compounds as substance P antagonists Inventor(s): Satake, Kunio; (Aichi-ken, JP) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030208079 Date filed: April 21, 2003 Abstract: This invention provides a compound of the formula: 1and its pharmaceutically acceptable salts, wherein R.sup.1 is C.sub.1-C.sub.6 alkyl; R.sup.2 is hydrogen, C.sub.1C.sub.6 alkyl, halo C.sub.1-C.sub.6 alkyl or phenyl; R.sup.3 is hydrogen or halo; R.sup.4 and R.sup.5 are independently hydrogen, C.sub.1-C.sub.6 alkyl or halo C.sub.1-C.sub.6 alkyl; and n is one, two or three.These compounds are useful as analgesics or antiinflammatory agents, or in the treatment of cardiovascular diseases, allergic disorders, angiogenesis, CNS disorders, emesis, gastrointestinal disorders, sunburn, urinary incontinence, or diseases, disorders or adverse conditions caused by Helicobacter pylori, or the like, in a mammalian subject, especially humans. Intermediates for preparation of the compounds of Formula (I) are also disclosed. Excerpt(s): This invention relates to novel piperidinylaminomethyl trifluoromethyl cyclic ether compounds and their pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and the use of such compounds as substance P antagonists. Substance P is a naturally occurring undecapeptide belonging to the tachykinin family of peptides, the latter being so-named because of their prompt stimulatory action on smooth muscle tissue. More specifically, substance P is a pharmaceutically active neuropeptide that is produced in mammals (having originally been isolated from gut) and possesses a characteristic amino acid sequence that is illustrated by D. F. Veber et al. in U.S. Pat. No. 4,680,283. The wide involvement of substance P and other tachykinins in the pathophysiology of numerous diseases has been amply demonstrated in the art. For instance, substance P has recently been shown to be involved in the transmission of pain or migraine, as well as in central nervous system disorders such as anxiety and schizophrenia, in respiratory and inflammatory diseases such as asthma and rheumatoid arthritis, respectively, and in gastrointestinal disorders and diseases of the GI tract, like ulcerative colitis irritable bowel syndrome,

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Crohn's disease, etc. It is also reported that tachykinin antagonists are useful for the treatment of cardiovascular diseases, allergic conditions, immunoregulation, vasodilation, bronchospasm, reflex or neuronal control of the viscera, senile dementia of the Alzheimer type, emesis, sunburn and Helicobacter pylori infection. International Patent Publication No. WO 97/08144 discloses a wide variety of substituted piperidine compounds, including piperidine compounds having a substituent comprising a fused ring moiety including an oxygen atom, as substance P antagonists. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pyrrolopyridazine compounds Inventor(s): Fujiwara, Hiroshi; (Ube-shi, JP), Hagihara, Masahiko; (Ube-shi, JP), Iwabuchi, Haruo; (Urawa-shi, JP), Matsunobu, Keiji; (Ube-shi, JP), Shibakawa, Nobuhiko; (Ube-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20040014762 Date filed: August 8, 2002 Abstract: A pyrrolopyridazine compound having the formula (I) or a pharmaceutically acceptable salt thereof: 1wherein, R.sup.1 is a C.sub.2-C.sub.6 alkenyl group, a halogeno C.sub.2-C.sub.6 alkenyl group, a C.sub.3-C.sub.7 cycloalkyl group which may be optionally substituted or a C.sub.3-C.sub.7 cycloalkyl- C.sub.1-C.sub.6 alkyl group which may be optionally substituted. R.sup.2 is a C.sub.1-C.sub.6 alkyl group. R.sup.3 is a hydroxymethyl group, a C.sub.2-C.sub.6 aliphatic acyloxymethyl group, a C.sub.6C.sub.10 arylcarbonyloxymethyl group which may be optionally substituted, a C.sub.1C.sub.6 alkoxycarbonyloxymethyl group, a formyl group, a carboxyl group, a C.sub.1C.sub.6 alkoxycarbonyl group or a C.sub.6-C.sub.10 aryloxycarbonyl group which may be optionally substituted. R.sup.4 is a C.sub.6-C.sub.10 aryl group which may be optionally substituted. A is an imino group, an oxygen atom or a sulfur atom. These compounds exhibit excellent gastric acid secretory inhibition activity and gastric mucous membrane protection activity etc. They are useful for prevention or treatment of ulcerative diseases and for Helicobacter pylori infections. Excerpt(s): This is a continuation application of international application PCT/JP01/00820 filed Feb. 6, 2001. This invention relates to pyrrolopyridazine derivatives or pharmaceutically acceptable salts thereof; to pharmaceutical compositions comprising a pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof (preferably compositions for the prevention or treatment of ulcerative disease) as an active ingredient; to the use of a pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof in the preparation of a pharmaceutical composition (preferably a composition for the prevention or treatment of ulcerative disease); or to a method for the prevention or treatment of disease (preferably ulcerative disease), which method comprises administering a pharmaceutically effective amount of a pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof to a warm-blooded animal (preferably a human). It has been considered that an inbalance between aggressive factors and protective factors against the gastric mucous membrane induces peptic ulcers. Gastric acid secretion is an aggressive factor and suppression of gastric acid secretion is useful in the prevention and treatment of the disease. Anticholinergic agents, histamine H.sub.2 receptor antagonists such as cimetidine and the like and proton pump inhibitors such as omeprazole and the like have been clinically used as a

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gastric acid secretion inhibitor. Although these agents are excellent therapeutic agents for ulcerative disease, the disease may recur after cessation of the therapy. It has been recently reported that Helicobacter pylon relates to recurrence of the ulcerative disease. Actually there have been some attempts to use a gastric acid secretion inhibitor in combination with an antibacterial agent for treatment of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Specific antibodies for use in preparation of pharmaceutical compositions useful in the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers Inventor(s): Ariga, Masato; (Saitama-ken, JP), Icatlo, Faustino C. JR.; (Gifu-shi, JP), Kimura, Nobutake; (Saitama-ken, JP), Kodama, Yoshikatsu; (Gifu-shi, JP) Correspondence: Platon N. Mandros; Burns, Doane, Swecker & Mathis, L.L.P.; P.O.BOX 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020197259 Date filed: June 24, 2002 Abstract: The present invention provides specific antibodies obtained from eggs laid by hens which have been immunized against urease of Helicobacter pylori as an antigen, and specific antibodies obtained from eggs laid by hens which have been immunized against flagella of Helicobacter pylori as an antigen. These antibodies are useful for the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers caused by infection of Helicobacter pylori. At least one organism selected from lactic acid bacteria, Enterococcuses, yeasts, and Baillus can be used along with the antibodies. Excerpt(s): The present invention relates to specific antibodies for use in preparing pharmaceutical compositions useful for the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers caused by infection of Helicobacter pylori (hereinafter referred to as H. pylori or Hp), and for use as an additive to foods useful for the prevention of gastritis, gastric ulcers and duodenal ulcers. At present it is believed that eradication of H. pylori in the stomach is essential for treating peptic ulcers fully. The combination of antibiotics and suppressors of gastric acid secretion has been generally proposed as a therapy for effective eradication of H. pylori as described below. H. pylori is a gram-negative spiral rod-shaped bacterium having some flagella at one end and inhabiting the human gastric mucosa. Marshall, B. J. and Warren, J. R. in Australia reported in 1983 that this bacterium was frequently detected in stomach biopsy specimens from patients with gastric ulcers. At that time this bacterium was named Campylobacter pylori since it resembles Campylobacter in morphology and growth characteristics. Later, it was found that the bacterium is different from Campylobacter in the fatty acid composition of its outer membrane and sequence of ribosome 16S-RNA. Therefore, the bacterium is now referred to as Helicobacter pylori and belongs to a newly established genus of Helicobacter. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Urease inhibitors Inventor(s): Kajiwara, Masahiro; (Saitama, JP) Correspondence: Finnegan, Henderson, Farabow, Garrett &; Dunner Llp; 1300 I Street, NW; Washington; DC; 20006; US Patent Application Number: 20030060482 Date filed: September 5, 2002 Abstract: A urease inhibitor and an anti-Helicobacter pylori agent, which contain, as an active ingredient, an isothiazole derivative represented by the general formula (1): 1wherein R.sup.1 represents a hydrogen atom or an amino group, R.sup.2 represents a hydrogen atom, a lower alkyl group, or an acetyl group, and X represents a carbon atom or a nitrogen atom. These drugs are effective to prevent and treat gastrointestinal diseases caused by urease of Helicobacter pylori, such as chronic gastritis and gastroduodenal ulcer. Excerpt(s): The present invention relates to a novel urease inhibitor and a novel antiHelicobacter pylori agent. It has recently been made clear that urease produced by Helicobacter pylori has a close relation to the development of gastrointestinal diseases such as chronic gastritis and gastroduodenal ulcer. The mechanism of gastric mucosa injury due to urease is considered as follows. Urea secreted from the gastric parietal is hydrolyzed by urease to produce ammonia and carbon dioxide. Ammonia has a strong mucosa injurious effect, thereby to cause a blood flow disorder of the gastric mucosa, and also neutralizes gastric acid, thereby to enable habitation of Helicobacter pylori within the stomach under a severe acidic environment. In case Helicobacter pylori adheres to the gastric mucosa, epithelial cells of the gastric mucosa produce Interleukin8 (IL-8) as a kind of cytokines, while IL-8 acts on neutrophils, thereby to cause migration and activation of neutrophils. The activated neutrophils form phagocytosis and phagosome and also cause production of active oxygen and degranulation. The produced active oxygen itself causes a mucosa injury and induced to hypochlorous acid through an action of chlorine and myeloperoxidase in the stomach, and is also converted into monochloramine by means of ammonia, thus causing a cell injury. 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 Helicobacter pylori, 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 “Helicobacter pylori” (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 Helicobacter pylori. You can also use this procedure to view pending patent applications concerning Helicobacter pylori. 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 5. BOOKS ON HELICOBACTER PYLORI Overview This chapter provides bibliographic book references relating to Helicobacter pylori. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Helicobacter pylori 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 “Helicobacter pylori” (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 Helicobacter pylori: •

Helicobacter Pylori Handbook Source: Oxford, England: Blackwell Science Ltd. 1995. 56 p. Contact: Available from Blackwell Science, Inc. 238 Main Street, Cambridge, MA 02142. (800) 215-1000 or (617) 876-7000. Fax (617) 492-5263. PRICE: $9.95. ISBN: 0865426597. Summary: The link between Helicobacter pylori infection and ulcer disease has been one of the most significant discoveries in gastroenterology in the past decade. The role of this organism in the development of nonulcer dyspepsia, gastric cancer, and lymphoma is also attracting interest. This monograph is designed to keep health care professionals whose specialty lies outside the field of gastroenterology abreast of this rapidly changing area. The author provides a concise, up to date review of H. pylori infection, current approaches to its diagnosis and treatment, and the position of H. pylori eradication in the management of gastrointestinal disorders. Written in outline

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format, the monograph covers epidemiology, transmission, the host response to infection, classification of gastritis, H. pylori and peptic ulcer disease or gastric cancer, H. pylori in children, diagnostic tests used to confirm infection, drug therapy, patient selection, and patients with dyspepsia. A list of further reading and a subject index appear at the end. 17 figures. 16 tables. 8 references. (AA-M).

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 “Helicobacter pylori” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Helicobacter pylori” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Helicobacter pylori” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Guide to Helicobacter Pylori by A. Axon; ISBN: 185873133X; http://www.amazon.com/exec/obidos/ASIN/185873133X/icongroupinterna

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Basic and Clinical Aspects of Helicobacter Pylori Infection by G. Gasbarrini (Editor), et al; ISBN: 0387567208; http://www.amazon.com/exec/obidos/ASIN/0387567208/icongroupinterna

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Basic and Clinical Aspects of Helicobacter Pylori Infection; ISBN: 3540567208; http://www.amazon.com/exec/obidos/ASIN/3540567208/icongroupinterna

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Clinical Pharmacology and Therapy of Helicobacter Pylori Infection (Progress in Basic and Clinical Pharmacology) by C. Scarpignato (Editor); ISBN: 3805576587; http://www.amazon.com/exec/obidos/ASIN/3805576587/icongroupinterna

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Clinicians' Manual on Helicobacter Pylori by G. Misiewicz MD, Adam Harris MD; ISBN: 1858732395; http://www.amazon.com/exec/obidos/ASIN/1858732395/icongroupinterna

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Gastroduodenal Disease and Helicobacter Pylori: Pathophysiology, Diagnosis and Treatment (Current Topics in Microbiology and Immunology, Vol 241) by T.U. Westblom (Editor), et al; ISBN: 3540650849; http://www.amazon.com/exec/obidos/ASIN/3540650849/icongroupinterna

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Gp Guide Helicobacter Pylori by Martin R; ISBN: 1860360130; http://www.amazon.com/exec/obidos/ASIN/1860360130/icongroupinterna

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Helicobacter Pylori by Uwe Blecker; ISBN: 1581120788; http://www.amazon.com/exec/obidos/ASIN/1581120788/icongroupinterna

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Helicobacter Pylori by John Calam; ISBN: 0412740001; http://www.amazon.com/exec/obidos/ASIN/0412740001/icongroupinterna

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Helicobacter Pylori by A. W. Harris, J. J. Misiewicz; ISBN: 0865426392; http://www.amazon.com/exec/obidos/ASIN/0865426392/icongroupinterna

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Helicobacter Pylori & Gastroduodenal Disease by Richard V. Heatley, B. J. Rathbone; ISBN: 0632033460; http://www.amazon.com/exec/obidos/ASIN/0632033460/icongroupinterna

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Helicobacter Pylori (La Gastroenterologia in Tasca) by F. Pace, S. Vigneri; ISBN: 8847000653; http://www.amazon.com/exec/obidos/ASIN/8847000653/icongroupinterna

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Helicobacter Pylori 1990: Proceedings of the Second International Symposium on Helicobacter Pylori Bad Nauheim, August 25 26th, 1989 by Gregor M., et al; ISBN: 0387526161; http://www.amazon.com/exec/obidos/ASIN/0387526161/icongroupinterna

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Helicobacter Pylori and Gastroduodenal Pathology by J. M. Pajares; ISBN: 3540554327; http://www.amazon.com/exec/obidos/ASIN/3540554327/icongroupinterna

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Helicobacter Pylori in Gastroduodenal Disease: (Slide Atlas) by Richard V. Heatley MD MRCP; ISBN: 0632035749; http://www.amazon.com/exec/obidos/ASIN/0632035749/icongroupinterna

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Helicobacter pylori in peptic ulcer disease (SuDoc HE 20.3046:12/1) by U.S. Dept of Health and Human Services; ISBN: B00010L288; http://www.amazon.com/exec/obidos/ASIN/B00010L288/icongroupinterna

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Helicobacter pylori in peptic ulcer disease : January 1988 through November 1993 : 1191 citations (SuDoc HE 20.3615/2:93-6) by Marian E. Beratan; ISBN: B00010HZUW; http://www.amazon.com/exec/obidos/ASIN/B00010HZUW/icongroupinterna

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Helicobacter Pylori in Peptic Ulceration and Gastritis by Barry J. Marshall, et al; ISBN: 0865421080; http://www.amazon.com/exec/obidos/ASIN/0865421080/icongroupinterna

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Helicobacter pylori Infection and Immunity (INFECTIOUS AGENTS AND PATHOGENESIS Volume 15) by Yoshimasa Yamamoto (Editor), et al; ISBN: 0306466589; http://www.amazon.com/exec/obidos/ASIN/0306466589/icongroupinterna

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Helicobacter Pylori Infection: New Facts - New Views by Peter Malfertheiner (Editor); ISBN: 3805572581; http://www.amazon.com/exec/obidos/ASIN/3805572581/icongroupinterna

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Helicobacter Pylori Infection: Pathophysiology, Epidemiology, and Management by T. C. Northfield, et al; ISBN: 0792388259; http://www.amazon.com/exec/obidos/ASIN/0792388259/icongroupinterna

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Helicobacter Pylori Protocols by Christopher L. Clayton (Editor), Harry L. T. Mobley (Editor); ISBN: 0896033813; http://www.amazon.com/exec/obidos/ASIN/0896033813/icongroupinterna

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Helicobacter Pylori, Gastritis and Peptic Ulcer by P. Malfertheiner (Editor), et al; ISBN: 0387520309; http://www.amazon.com/exec/obidos/ASIN/0387520309/icongroupinterna

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Helicobacter Pylori, Gastritis and Peptic Ulcer; ISBN: 3540520309; http://www.amazon.com/exec/obidos/ASIN/3540520309/icongroupinterna

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Helicobacter pylori. Von der Grundlage zur Therapie. Eigenschaften, Pathogenese, Klinik, Nachweis, Eradikation. by Peter Malfertheiner (Author); ISBN: 3131274034; http://www.amazon.com/exec/obidos/ASIN/3131274034/icongroupinterna

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Helicobacter Pylori: An Atlas by A. Price (Editor), et al; ISBN: 1858730848; http://www.amazon.com/exec/obidos/ASIN/1858730848/icongroupinterna

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Helicobacter Pylori: Basic Mechanisms to Clinical Cure 1996 by Richard H. Hunt (Editor), Guido N. Tytgat (Editor); ISBN: 0792387171; http://www.amazon.com/exec/obidos/ASIN/0792387171/icongroupinterna

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Helicobacter pylori: Basic Mechanisms to Clinical Cure 2000 by Richard H. Hunt (Editor), et al; ISBN: 0792387643; http://www.amazon.com/exec/obidos/ASIN/0792387643/icongroupinterna

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Helicobacter Pylori: Basic Mechanisms to Clinical Cure, 1998 by R.H. Hunt (Editor), Guido N.J. Tytgat (Editor); ISBN: 0792387392; http://www.amazon.com/exec/obidos/ASIN/0792387392/icongroupinterna

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Helicobacter Pylori: Basic Mechanisms to Clinical Cure, 2002: The Proceedings of a Symposium Organised by Axcan Pharma Held in Maui, Hawaii, November 10-13, 2002 by Richard H. Hunt (Editor), Guido N. J. Tytgat (Editor); ISBN: 0792387902; http://www.amazon.com/exec/obidos/ASIN/0792387902/icongroupinterna

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Helicobacter Pylori: Biology and Clinical Practice by C. Stewart Goodwin (Editor), Bryan W. Worsley (Editor); ISBN: 0849364515; http://www.amazon.com/exec/obidos/ASIN/0849364515/icongroupinterna

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Helicobacter Pylori: Its Role in Gastrointestinal Disease by Anthony Axon (Editor); ISBN: 185873018X; http://www.amazon.com/exec/obidos/ASIN/185873018X/icongroupinterna

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Helicobacter Pylori: Molecular & Cellular Biology by Mark Achtman (Editor), Sebastian Suerbaum (Editor); ISBN: 1898486255; http://www.amazon.com/exec/obidos/ASIN/1898486255/icongroupinterna

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Helicobacter Pylori: Physiology and Genetics by Harry L. T. Mobley (Editor), et al; ISBN: 1555812139; http://www.amazon.com/exec/obidos/ASIN/1555812139/icongroupinterna

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Helicobacter Pylori: Techniques for Clinical Diagnosis and Basic Research by Adrian Lee, Francis Megraud (Contributor); ISBN: 0702019992; http://www.amazon.com/exec/obidos/ASIN/0702019992/icongroupinterna

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Pathogenesis & Host Response in Helicobacter Pylori Infections by A. P. Moran (Editor); ISBN: 092659219X; http://www.amazon.com/exec/obidos/ASIN/092659219X/icongroupinterna

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Pediatric Helicobacter Pylori Infection by Uwe Blecker by Uwe Blecker; ISBN: 1581127812; http://www.amazon.com/exec/obidos/ASIN/1581127812/icongroupinterna

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The Helicobacter Pylori Handbook by Richard V. Heatley; ISBN: 0632051760; http://www.amazon.com/exec/obidos/ASIN/0632051760/icongroupinterna

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The Immunobiology of H. Pylori: From Pathogenesis to Prevention by Peter B. Ernst (Editor), et al; ISBN: 0397587651; http://www.amazon.com/exec/obidos/ASIN/0397587651/icongroupinterna

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

Helicobacter Pylori-Related Diseases: Demographics, Epidemiology, and Pathophysiology of Gastritis, Ulcers, and Cancer Source: in Freston, J.W. Diseases of the Gastroesophageal Mucosa: The Acid-Related. Totowa, NJ: The Humana Press, Inc. 2001. p.29-41. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail: [email protected] PRICE: $99.50, plus shipping and handling. ISBN: 089603965X. Summary: Gastric acid-related diseases are among the most commonly encountered disorders in clinical practice. This chapter on the demographics, epidemiology, and pathophysiology of gastritis, ulcers and cancer is from a text that emphasizes the diagnosis and treatment of these conditions. Helicobacter pylori is a common bacterial infection of the gastric mucosa. The infection is generally asymptomatic, but it may cause a variety of gastrointestinal diseases that are associated with significant morbidity and mortality. In some cases, increased acid secretion can lead to the formation of duodenal ulcers. In other hosts, acid secretion may be reduced, leading to an association with gastric ulcers as well as gastric carcinoma and lymphoma. Topics include prevalence of H. pylori in developing countries, host factors, route of transmission, reinfection, bacteriology, virulence factors, acute versus chronic gastritis, the pathogenesis of ulcer formation, and the pathogenesis of H. pylori and gastric cancer. 1 table. 45 references.

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Helicobacter Pylori: Epidemiology and Pathogenesis Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 249-254. 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. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Helicobacter pylori (H. pylori) is the leading cause of gastric and duodenal ulcers, and it has been associated with gastric neoplasia, both adenocarcinoma and lymphoma (stomach cancers). In most people, however, infection is a symbiotic situation in which minor histologic changes occur in the gastric mucosa (stomach lining) that are without clinical consequence, despite a lifetime presence of the organism. This chapter on the epidemiology and pathogenesis of H. pylori is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The author reviews the present understanding of the epidemiology and transmission of H. pylori. The prevalence of H. pylori in the

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developing world is remarkable in that most of the population is infected. Infection is acquired in childhood, much like most other enteric infections, but H. pylori infection differs in that it is a persistent infection that may last a lifetime yet cause no ill effects in the host. The prevalence of H. pylori infection in the developed world has fallen dramatically during the past 50 years. The most recent data for children suggest that H. pylori will become rare because of improving socioeconomic status and improving sanitation. The routes of infection include oral to oral, fecal to oral, or environmental transmission. Eradication of the organism can reduce the recurrence rate of most duodenal and gastric ulcers, may reduce the incidence of gastric cancer, but is unlikely to have a significant impact on dyspepsia (heartburn). The author concludes that little is known about the mode of transmission of H. pylori or its pathogenesis, but both of these areas are the focus of intense research. 2 figures. 4 tables. 28 references. •

Helicobacter Pylori and Peptic Ulcer Disease Source: in Chung, P. and Kim, K.E. Acute Gastrointestinal Bleeding: Diagnosis and Treatment. Totowa, NJ: Humana Press. 2003. p. 35-56. Contact: Available from Humana Press. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail: [email protected]. Website: www.humanapress.com. PRICE: $99.50; plus shipping and handling. ISBN: 588290042. Summary: Peptic ulcer disease (PUD) is a common gastrointestinal (GI) problem that has a substantial impact on patient well-being and health care costs. Complications include hemorrhage, perforation, and gastric outlet obstruction. This chapter on Helicobacter pylori and PUD is from a textbook in which leading experts in the fields of gastroenterology, surgery, and radiology comprehensively review the pathophysiology, diagnosis, management, and treatment of acute bleeding disorders of the GI tract. Topics covered in this chapter include epidemiology, clinical presentation, diagnosis, etiology, treatment, and bleeding associated with PUD. Peptic ulcer can present silently with complications such as hemorrhage, particularly in patients on nonsteroidal antiinflammatory drugs (NSAIDs). Proton pump inhibitors (PPI) are the mainstays of therapy. Effective eradication of H. pylori involves regimens utilizing multiple antibiotics. Upper endoscopy effectively diagnoses peptic ulcers, reduces rebleeding, and allows for appropriate triage of patients with upper GI bleeding complications. One patient care algorithm is provided. 1 figure. 3 tables. 99 references.

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Helicobacter Pylori: Diagnostic Testing and Treatment Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 255-264. 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. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: This chapter on the diagnosis and treatment of Helicobacter pylori (H. pylori) is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. Many highly sensitive and specific diagnostic modalities have been developed to establish whether a patient is infected with H. pylori. The author stresses that physicians must understand the scientific basis and comparative accuracy of these methods to choose the most appropriate test. Tests described include rapid urease tests, histology, culture, antibody detection, and urea breath tests. When the decision is made

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to test for H. pylori, treatment should be initiated in those found to be infected. Antibiotic regimens against H. pylori infection have evolved from monotherapy and random combinations to clinically well studied combinations with reliable eradication rates. The author concludes with a brief review of current research efforts in this area, including the development of a vaccine for H. pylori infection, and topical therapy for H. pylori infection. 4 figures. 7 tables. 21 references. •

Ulcer Disease and Helicobacter Pylori Infection: Etiology and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 66-90. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: This chapter on ulcer disease and Helicobacter pylori infection is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors of this chapter review and present the evidence for the etiological (causative) role of H. pylori in peptic ulcer disease. They also summarize the evidence for effective treatments for ulcer disease based on the approach of eradication of the infection. H. pylori is now accepted as a definite pathogen that fulfills almost all of the criteria for causation. H. pylori eradication results in cure of ulcer disease and markedly reduces ulcer recurrence and ulcer complications, such as bleeding. Eradication of H. pylori heals ulcers without the need to continue the use of ulcer healing drugs, heals refractory ulcers, and also results in faster ulcer healing than occurs with traditional acid suppressive therapy. Effective therapies to eradicate H. pylori are now available; the authors summarize present recommendations for first line therapy, as of 1999. Further recommendations on optimal treatments for treatment failures and antibiotic resistant infections require more definitive data. 6 tables. 222 references.

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Helicobacter Pylori Infection, a Paradigm for Chronic Mucosal Inflammation: Pathogenesis and Implications for Eradication and Prevention Source: in Schrier, R.W., et al., eds. Advances in Internal Medicine. Vol 41. St. Louis, MO: Mosby-Year Book, Inc. 1996. p. 85-117. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail: [email protected]. PRICE: $72.95. ISBN: 0815183143. ISSN: 00652822. Summary: This chapter, from a yearbook of advances in internal medicine, covers the role of Helicobacter pylori infection in chronic mucosal inflammation, focusing on its pathogenesis and on implications for its eradication and prevention. After a brief section on the history of medical understanding of H. pylori, the authors discuss microbiology and epidemiology; clinical features, including acute infection, peptic ulcer disease, atrophic gastritis and gastric cancer, and gastric lymphoma; pathogenesis, including colonization of the gastric mucosa, gastric inflammation, characteristics of H. pylori strains associated with increased virulence, and microecologic perspectives; and treatment options, including the prospects for a vaccine. Four antibiotics to which H. pylori is susceptible in vivo are amoxicillin, tetracycline, clarithromycin, and metronidazole; bismuth salts are also included in many drug regimens. The authors

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conclude by reporting on animal studies on immunization against H. pylori. 3 figures. 3 tables. 214 references.

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CHAPTER 6. MULTIMEDIA ON HELICOBACTER PYLORI Overview In this chapter, we show you how to keep current on multimedia sources of information on Helicobacter pylori. 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 Helicobacter pylori is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “Helicobacter pylori” 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 “Helicobacter pylori” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on Helicobacter pylori: •

Clinical Case Reviews: Management of H. Pylori in Gastrointestinal Disease Source: Secaucus, NJ: Network for Continuing Medical Education. 1995. (videocassette). Contact: Available from Network for Continuing Medical Education. 1425 Broad Street, Clifton, NJ 07013. (800) 223-0272 or (973) 473-9500. Fax (973) 591-1224. Order Number: S102. PRICE: Call for pricing information. Summary: Helicobacter pylori (H. pylori) is now known to be an etiology in more than 90 percent of peptic ulcer cases. This knowledge has led to the evolution of therapies that make it possible to cure nearly all ulcers. This medical continuing education program reviews the management of H. pylori in gastrointestinal disease and presents three case studies involving H. pylori in peptic ulcer disease. The first section explores the discovery of H. pylori as an etiologic factor in peptic ulcer, including the history and evolution of this discovery (Marshall and Warren's research). The next section discusses the three possible mechanisms of gastric mucosal injury caused by H. pylori (ammonia,

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cytotoxins, and mucosal immune response). The instructional portion of the videotape also covers the types of illnesses related to H. pylori (from asymptomatic gastritis to PUD), the incidence and other epidemiologic factors of the infection, transmission, the role of H. pylori infection in ulcer recurrence rates, diagnostic tests, drug therapy regimens, and patient selection issues. The remaining portion of the tape presents three case studies. The video features live action of real physicians and patients, and graphics and anatomic illustrations.

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CHAPTER 7. PERIODICALS AND NEWS ON HELICOBACTER PYLORI Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Helicobacter pylori.

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

Helicobacter pylori plays complex role in esophageal cancer Source: Reuters Medical News Date: March 02, 2004

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Lipid profile improves after Helicobacter pylori eradication Source: Reuters Industry Breifing Date: February 18, 2004

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H. pylori tied to plaque instability and stroke Source: Reuters Medical News Date: February 09, 2004

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Eradicating H. pylori after gastric lesions appear may not prevent malignancy Source: Reuters Industry Breifing Date: January 13, 2004

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Helicobacter pylori eradication may cure low-grade gastric lymphoma Source: Reuters Industry Breifing Date: January 09, 2004

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One-day therapy eradicates Helicobacter pylori in patients with dyspepsia Source: Reuters Industry Breifing Date: October 02, 2003

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Maintenance therapy not needed after H. pylori eradication with bleeding ulcers Source: Reuters Medical News Date: September 22, 2003

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H. pylori cytotoxin inhibits T cell activation Source: Reuters Medical News Date: August 21, 2003

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H. pylori CagA protein causes gastric damage by disrupting epithelial junctions Source: Reuters Medical News Date: May 29, 2003

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Test-and-treat strategy for H. pylori modestly effective, but not cost saving Source: Reuters Industry Breifing Date: May 27, 2003

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H. pylori infection may protect against esophageal cancer Source: Reuters Medical News Date: May 21, 2003

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Instance of gastric lymphoma remission reported with H. pylori eradication alone Source: Reuters Medical News Date: April 14, 2003

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Aspirin kills H. pylori and increases its susceptibility to antibiotics Source: Reuters Industry Breifing Date: April 04, 2003

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H. pylori may cause ulcers by altering tyrosine phosphatase signaling Source: Reuters Medical News Date: February 25, 2003

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H. pylori test reliable even in setting of proton pump inhibitor therapy Source: Reuters Industry Breifing Date: February 18, 2003

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Halitosis could be marker for Helicobacter pylori infection Source: Reuters Industry Breifing Date: January 31, 2003

Periodicals and News

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H. pylori treatment not indicated for functional dyspepsia Source: Reuters Industry Breifing Date: January 14, 2003

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Whole cell vaccine effective against H. pylori infection and reinfection in mice Source: Reuters Industry Breifing Date: December 24, 2002

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Oridion wins FDA nod for final H. pylori breath test component Source: Reuters Industry Breifing Date: December 18, 2002

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H. pylori vaccine elicits humoral and cellular mucosal immune response Source: Reuters Industry Breifing Date: November 28, 2002

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H. pylori and IL-1 genotyping may predict gastric cancer risk Source: Reuters Medical News Date: November 19, 2002

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Azithromycin deemed unsuitable for treatment of H. pylori Source: Reuters Industry Breifing Date: November 15, 2002

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FDA approves rabeprazole for 7-day treatment of H. pylori infection Source: Reuters Medical News Date: November 14, 2002

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Eisai's Aciphex cleared for seven-day treatment of H. pylori infection Source: Reuters Industry Breifing Date: November 14, 2002

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H. pylori infection may explain familial clustering of gastric cancer Source: Reuters Medical News Date: October 18, 2002

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Helicobacter pylori, peptic ulcer disease underdiagnosed in elderly patients Source: Reuters Industry Breifing Date: October 16, 2002

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H. pylori infection influences gastric manifestations of familial polyposis Source: Reuters Medical News Date: October 02, 2002

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Treatment of H. pylori infection reduces occurrence of NSAID-related ulcers Source: Reuters Industry Breifing Date: September 12, 2002

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Intimate contact not likely to transmit H. pylori Source: Reuters Medical News Date: September 12, 2002

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H. pylori eradication may improve glucose control in diabetic children Source: Reuters Medical News Date: September 10, 2002

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Manufacturing issues hold up approval of Axcan H. pylori drug Source: Reuters Industry Breifing Date: August 13, 2002

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Infected moms may transmit H. pylori to children Source: Reuters Health eLine Date: July 29, 2002

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Virulent H. pylori adheres to inflamed gastric mucosa Source: Reuters Industry Breifing Date: July 26, 2002

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H. pylori linked with increase in reproductive disorders Source: Reuters Medical News Date: July 26, 2002

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Virulent form of H. pylori linked to atherosclerotic stroke Source: Reuters Medical News Date: July 08, 2002

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Helicobacter pylori infection appears to elevate coronary heart disease risk Source: Reuters Medical News Date: July 04, 2002

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Oral transmission of Helicobacter pylori unlikely Source: Reuters Medical News Date: June 21, 2002

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Glaucoma patients may benefit from Helicobacter pylori eradication Source: Reuters Medical News Date: June 10, 2002

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H. pylori infection facilitates aspirin-induced stomach damage Source: Reuters Industry Breifing Date: May 27, 2002

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Endoscopy adds little to breath testing for H. pylori infection Source: Reuters Industry Breifing Date: April 25, 2002

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H. pylori acquisition rates higher among blacks and young children Source: Reuters Medical News Date: March 15, 2002

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CagA+ Helicobacter pylori strains are declining faster than cagA- strains Source: Reuters Medical News Date: March 12, 2002

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H. pylori drug resistance a growing problem in Germany Source: Reuters Industry Breifing Date: March 06, 2002

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Mertek wins FDA nod for H. pylori breath test Source: Reuters Industry Breifing Date: February 04, 2002

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New short-term quadruple H. pylori eradication regimen safe and effective Source: Reuters Industry Breifing Date: January 30, 2002

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H. pylori infection plus NSAID use synergistically increases peptic ulcer risk Source: Reuters Industry Breifing Date: January 03, 2002

Periodicals and News

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H. pylori's CagA deregulates gastric cell protein to induce abnormal proliferation Source: Reuters Medical News Date: December 13, 2001

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H. pylori may increase laryngeal cancer risk Source: Reuters Medical News Date: November 23, 2001

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Eradication of H. pylori may improve symptoms of hereditary skin disorder Source: Reuters Industry Breifing Date: November 16, 2001

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H. pylori peptide activates monocytes to impair lymphocyte function Source: Reuters Medical News Date: October 15, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Helicobacter pylori” (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 “Helicobacter pylori” (or synonyms). If you know the name of a company that is relevant to Helicobacter pylori, you can go to any stock trading Web site (such as

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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 “Helicobacter pylori” (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 “Helicobacter pylori” (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 Helicobacter pylori: •

Helicobacter Pylori Infection and Gastric Cancer in the Asia Pacific Region Source: Asian Pacific Gastroenterology News. Issue 4: 11. June 2000. Contact: Available from Blackwell Science Asia. 54 University Street, Carlton, Victoria 3053, Australia. 61 3 9347 0300. Fax 61 3 9347 5001. E-mail: [email protected]. Summary: Helicobacter pylori infection causes histological gastritis; chronic gastritis from long term H. pylori infection results in gastric mucosal atrophy, which eventually progresses to intestinal metaplasia and sometimes to gastric (stomach) cancer. This brief article reviews the problem of H. pylori infection and gastric cancer in the Asia Pacific region. The author reports data that show just over 10 percent of H. pylori infected persons in Japan may develop gastric cancer. The prevalence of asymptomatic H. pylori infection differs greatly between countries, being low in developed countries and high in developing countries. Because H. pylori is transmitted via the fecal to oral route, and children are more readily infected than adults, the author notes that conducting a survey on H. pylori infection is the same as assessing the water supply and sewage systems of a country. The present prevalence of H. pylori infection in Japan is extremely low at an early age, as in other developed countries, and subsequently shows a rapid increase until it reaches a plateau of approximately 70 percent at 50 years of age. The author also explores the different incidence of gastric cancer as it varies between countries. It is suggested that H. pylori infection leads to histological chronic gastritis, regardless of the strain of the organism, and after that the course of the disease depends on environmental factors (diet, age), virulence of H. pylori strains, and host factors including genetics. The author concludes by calling for additional research collaboration between countries in the Asia Pacific region. 1 figure.

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Academic Periodicals covering Helicobacter Pylori Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Helicobacter pylori. In addition to these sources, you can search for articles covering Helicobacter pylori 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 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Helicobacter pylori. 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 Helicobacter pylori. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Helicobacter pylori: Bismuth Subsalicylate, Metronidazole, and Tetracycline--for H. Pylori •

Systemic - U.S. Brands: Helidac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203633.html

Clarithromycin •

Systemic - U.S. Brands: Biaxin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202667.html

Lansoprazole •

Systemic - U.S. Brands: Prevacid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202787.html

Metronidazole •

Systemic - U.S. Brands: Flagyl; Protostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html

Omeprazole •

Systemic - U.S. Brands: Prilosec http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202423.html

Penicillins •

Systemic - U.S. Brands: Amoxil; Bactocill; Beepen-VK; Betapen-VK; Bicillin L-A; Cloxapen; Crysticillin 300 A.S.; Dycill; Dynapen; Geocillin; Geopen; Ledercillin VK; Mezlin; Nafcil; Nallpen; Omnipen; Omnipen-N; Pathocil; Pen Vee K; Pentids; Permapen; Pfizerpen; Pfizerpen-AS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202446.html

Urea C 14 •

Diagnostic - U.S. Brands: PYtest http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203517.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/.

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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

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

•

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

•

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

•

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

•

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

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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/

10

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

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

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

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

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

•

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

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

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

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

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

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

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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/

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

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

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Helicobacter pylori” (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 18055 129 770 94 27 19075

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “Helicobacter pylori” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Helicobacter Pylori In the following section, we will discuss databases and references which relate to the Genome Project and Helicobacter pylori. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Helicobacter pylori” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for Helicobacter pylori: •

Helicobacter Pylori Infection, Susceptibility to Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600263 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Helicobacter pylori” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “Helicobacter pylori” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

22

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Helicobacter pylori can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 Helicobacter pylori. 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 Helicobacter pylori. 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 “Helicobacter pylori”:

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Other guides Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Peptic Ulcer http://www.nlm.nih.gov/medlineplus/pepticulcer.html Stomach Cancer http://www.nlm.nih.gov/medlineplus/stomachcancer.html Stomach Disorders http://www.nlm.nih.gov/medlineplus/stomachdisorders.html

Within the health topic page dedicated to Helicobacter pylori, the following was listed: •

General/Overviews JAMA Patient Page: Peptic Ulcers Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZA5EFJUSC &sub_cat=194

•

Diagnosis/Symptoms Endoscopy/Gastroscopy Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/endogastro.pdf Helicobacter pylori Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/hpylori/test.html Upper Endoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm Upper GI Series Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/uppergi/index.htm

•

Treatment H. pylori: The Key to Cure for Most Ulcer Patients Source: Centers for Disease Control and Prevention http://www.cdc.gov/ulcer/keytocure.htm History of Ulcer Diagnosis and Treatment Source: Centers for Disease Control and Prevention http://www.cdc.gov/ulcer/history.htm

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Ulcers: What You Can Do to Heal Your Ulcer Source: American Academy of Family Physicians http://familydoctor.org/186.xml •

Specific Conditions/Aspects Bleeding Ulcers Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00086 Gastritis Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/gastritis/index.htm Have a Stressful Job? You Must Have an Ulcer.Right? Source: Centers for Disease Control and Prevention http://www.cdc.gov/ulcer/myth.htm NSAIDs and Peptic Ulcers Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/nsaids/index.htm Zollinger-Ellison Syndrome Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/zollinger/index.htm

•

Children Peptic Ulcers Source: Nemours Foundation http://kidshealth.org/parent/medical/digestive/peptic_ulcers.html Ugh! Ulcers Source: Nemours Foundation http://kidshealth.org/kid/grownup/conditions/ulcers.html

•

From the National Institutes of Health H. pylori and Peptic Ulcer Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/hpylori/index.htm What I Need to Know about Peptic Ulcers Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/pepticulcers_ez/index.htm

•

Latest News Wiping Out Stomach Bug Improves Cholesterol Level Source: 02/18/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16136 .html

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Organizations American College of Gastroenterology http://www.acg.gi.org/ American Gastroenterological Association http://www.gastro.org/ National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

•

Prevention/Screening Digestive Health Tips Source: American College of Gastroenterology http://www.acg.gi.org/patientinfo/healthtips/index.html

•

Research Combination Treatment for Peptic Ulcers at High Risk for Recurrent Bleeding Source: American College of Physicians http://www.annals.org/cgi/content/full/139/4/I-12 Effects of Antibiotic Treatment for Helicobacter pylori on Normal Bowel Bacteria Source: American College of Physicians http://www.annals.org/cgi/content/full/139/6/I-42 Past Antibiotic Use Affects Resistance and Outcomes of Helicobacter pylori Infection Source: American College of Physicians http://www.annals.org/cgi/content/full/139/6/I-10

•

Teenagers Ulcers Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/digestive/ulcers.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 Helicobacter pylori. CHID offers summaries

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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: •

H. pylori in Children Source: Flourtown, PA: American Society for Pediatric Gastroenterology, Hepatology and Nutrition. 2003. 1 p. Contact: Available from North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). PO Box 6, Flourtown, PA 19031. (215) 2330808. Fax: (215) 233-3939. Website: www.naspgn.org. PRICE: Full-text available online at no charge; contact organization for print copies. Summary: Helicobacter pylori is a common bacteria that infects the stomach. Most of those infected never experience any symptoms and have no signs of disease. However, some adults and a small number of children with the infection will develop inflammation and even ulcers of the stomach or the small intestine. This brief fact sheet considers H. pylori infection in children. The fact sheet defines the condition, then discusses diagnostic tests used to identify and confirm the problem, and treatment options. Triple antibiotic therapy is recommended for children who have active H. pylori infection and who are experiencing pain, nausea, poor appetite, or heartburn, and those in whom ulcers have been found during an endoscopy. For more information, readers are encouraged to visit www.naspghan.org (the web site of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition).

•

Do You Have H. Pylori? Source: Research Triangle Park, NC: Glaxo Wellcome, Inc. 1996. 2 p. Contact: Available from Glaxo Wellcome Education Resource Center. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free; bulk copies available. Summary: Recent discoveries have shown that an important cause of most duodenal ulcers may be an infection with a bacterium called Helicobacter pylori. This brochure familiarizes readers with H. pylori and its potential role in duodenal ulcers. While stress and diet may play a role in aggravating an ulcer, it is likely that H. pylori is usually the root cause. This enables treatment programs that eliminate H. pylori and reduce the risk of ulcer recurrence. The brochure describes duodenal ulcers and their symptoms; how H. pylori could cause an ulcer; how to know if H. pylori is implicated in an individual patient; and the good chance of success in eradicating H. pylori. The back cover of the brochure summarizes the basic facts covered in the text. One illustration depicts the bacterium itself; another shows a simple outline of the stomach, with the duodenum labelled. 2 figures.

•

Gastritis, Ulcers and Helicobacter Pylori Source: Overland Park, KS: Tri-Med Specialties, Inc. 199x. 2 p. Contact: Available from Tri-Med Specialties, Inc. P.O. Box 23306, Overland Park, KS 66223. (800) 874-6331. PRICE: Free. Available only to medical professionals.

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Summary: This brochure provides information for patients about helicobacter pylori (H. pylori) infections. It defines H. pylori infection, describes its symptoms, and explains the relationship between H. pylori and ulcers. It then discusses diagnosis and treatment. A list of references for further information is included. •

Helicobacter Pylori Source: Bethesda, MD: American Gastroenterological Association. 1996. 2 p. Contact: Available from GIDH-AGA Patient Education Center. P.O. Box 1274, West Caldwell, NJ 07007-9562. PRICE: 25 copies free to health care professionals for distribution to patients. Summary: This brochure provides patients with basic information about Helicobacter pylori, a bacteria that can cause inflammation of the stomach lining (gastritis) that can lead to ulcers in the stomach and duodenum. An ulcer is a sore or wound in the lining of the stomach or the duodenum that may cause pain or bleeding. Topics include diagnostic tests used to confirm H. pylori infection, treatment options, and the results of eradicating H. pylori infections. Doctors do not know for certain how H. pylori is spread, although it is usually acquired in childhood. For most people with H. pylori infection, elimination of the infection may have no noticeable effect on their health or sense of well-being. However, for those patients who have or have had a duodenal ulcer in the past, successful elimination of the bacteria can reduce the risk of ulcer recurrence. The brochure concludes with a glossary of terms. 3 figures. (AA-M).

•

Helicobacter Pylori Infection (Gastritis) Source: in Sodeman, W.A., Jr. Instructions for Geriatric Patients. Philadelphia, PA: W.B. Saunders Company. 1995. p. 110-111. 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: $38.95. ISBN: 0721643353. Summary: This chapter, from a book of instructions for geriatric patients, provides a basic information sheet on Helicobacter pylori infection (gastritis). H. pylori infections tend to become chronic or long lasting, although they usually cause no complaints or symptoms. But in some people, this chronic infection can lead to the development of stomach and duodenal ulcers. H. pylori infections are not difficult to eradicate, but they do require the use of two or three drugs. The fact sheet outlines the drugs commonly used, including omeprazole (Prilosec), amoxicillin, metronidazole (Flagyl), and bismuth (Pepto-Bismol). The author notes that the timing of treatment for H. pylori infections will take into consideration other health care problems that may need more urgent or immediate treatment. The information sheet concludes by reminding readers to contact their health care provider if they miss more than a single dose of a drug regimen to eradicate H. pylori. The instructions are designed to supplement and reinforce physician instructions to their patients. (AA-M).

•

Helicobacter Pylori in Gastrointestinal Disease Source: Arlington, VA: American College of Gastroenterology. 1995. 24 p. Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206. (703) 549-4440. PRICE: Single copy free.

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Summary: This continuing education booklet helps physicians understand the role of Helicobacter pylori in peptic ulcer disease, gastric cancer, and nonulcer dyspepsia. Topics include the invasive and noninvasive methods for diagnosing H. pylori; the various treatment options for H. pylori, including traditional and emerging therapies; issues of resistance and compliance as they relate to H. pylori therapies; and the purpose, findings, and recommendations of the NIH Consensus Panel for H. pylori. The booklet includes a posttest with which readers can qualify for 1 hour of continuing medical education credit. 9 figures. 40 references. •

NIH Consensus Statement: Helicobacter Pylori in Peptic Ulcer Disease Source: Bethesda, MD: NIH Office of Medical Applications of Research. 1994. 24 p. Contact: Available from NIH Consensus Program Information Service. P.O. Box 2577 Kensington, MD 20891. (800) 644-6627. PRICE: Single copy free. Summary: This document presents the National Institutes of Health Consensus Statement from a Consensus Development Conference held in February 1994 on Helicobacter pylori (H. pylori) in peptic ulcer disease. The Conference addressed six areas: the causal relationship of H. pylori to upper gastrointestinal disease; the diagnosis and eradication of H. pylori infection; how eradication of H. pylori infection benefits the patient with peptic ulcer disease; the relationship between H. pylori infection and gastric malignancy; which H. pylori-infected patients should be treated; and the questions that must be addressed by future research in this area. The Consensus Statement lists three conclusions: ulcer patients with H. pylori infection require treatment with antimicrobial agents in addition to anti-secretory drugs whether on first presentation with the illness or on recurrence; the value of treating non-ulcer dyspepsia patients with H. pylori infection remains to be determined; and the interesting relationship between H. pylori infection and stomach cancers requires further exploration. The document concludes with a list of the panel members and their affiliations. 1 table. (AA-M).

•

Treating Stomach Ulcers and H. Pylori Infection Source: American Family Physician. 55(8): 2784-2786. June 1997. Summary: This patient education handout provides information about stomach ulcers and Helicobacter pylori infection. Written in a question and answer format, the handout defines an ulcer and then covers the complications associated with ulcers, the causes of ulcers, risk factors for ulcers, treatment options, the side effects of medications taken to eradicate H. pylori, and the role of diet therapy in treating ulcers. The handout emphasizes that most people with ulcers have a bacterial infection (H. pylori) in their stomachs. Minor side effects of H. pylori medicines include a black color on the tongue and black stool, diarrhea, nausea, and headache. These side effects are usually minor and go away on their own. In addition, patients with ulcers are counseled not to smoke and to avoid using aspirin or ibuprofen. The handout is designed to be duplicated and distributed by physicians to their patients. (AA-M).

•

Understanding H. Pylori Source: Nurse Practitioner. 25(8): 48. August 2000. Contact: Available from Nurse Practitioner. Circulation Department, P.O. Box 5053, Brentwood, TN 37024-5053. (800) 490-6580. Fax (615) 377-0525.

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Summary: This patient education handout reviews Helicobacter pylori, the most common chronic bacterial infection in the world, colonizing the stomachs of more than 50 percent of the human population. Many people have no signs that they are infected, but others may have a burning stomach pain, nausea, vomiting, and reduced appetite. The infection weakens the lining of the stomach and may lead to an ulcer. H. pylori infection has been associated with gastritis, ulcers, stomach tumors, and iron deficiency anemia. In the United States, approximately 20 percent of the population may be infected. Children and adults can be infected with H. pylori, although infection rates increase as one gets older. H. pylori testing is done through a blood test, a breath test, or by endoscopy. H. pylori is treated with a combination of drugs that kill bacteria (antibiotics) and drugs that suppress the acid in the stomach. Reinfection rarely occurs after successful treatment of H. pylori. If symptoms remain after treatment, the patient is usually referred to a gastroenterologist (a digestive specialist). The fact sheet concludes with the contact address for the National Digestive Diseases Information Clearinghouse (NDDIC), for patients wishing to obtain additional information. 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 “Helicobacter pylori” (or synonyms). The following was recently posted: •

Dyspepsia Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 October (revised 2003 Jan); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3664&nbr=2890&a mp;string=Helicobacter+AND+pylori

•

Dyspepsia. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2003 March; 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3723&nbr=2949&a mp;string=Helicobacter+AND+pylori

•

Evaluation of dyspepsia Source: American Gastroenterological Association - Medical Specialty Society; 1997 November 8 (reviewed 2001); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1295&nbr=529&am p;string=Helicobacter+AND+pylori

Patient Resources

•

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Helicobacter pylori infection in children: recommendations for diagnosis and treatment Source: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition - Professional Association; 2000 November; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3594&nbr=2820&a mp;string=Helicobacter+AND+pylori

•

Management of gastroesophageal reflux disease (GERD) Source: University of Michigan Health System - Academic Institution; 2002 March; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3372&nbr=2598&a mp;string=Helicobacter+AND+pylori

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Peptic ulcer disease Source: University of Michigan Health System - Academic Institution; 1996 October (revised 1999 May); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2286&nbr=1512&a mp;string=Helicobacter+AND+pylori

•

Procedure guideline for C-14 urea breath test Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1998 June (updated 2001 Jun 23); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2947&nbr=2173&a mp;string=Helicobacter+AND+pylori

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Use of antibiotics in paediatric care Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 March; 109 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3436&nbr=2662&a mp;string=Helicobacter+AND+pylori 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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Helicobacter pylori (H. pylori) Page - Centers for Disease Control and Prevention (CDC) Summary: Visit this web site for information about H. pylori infection and ulcers prepared by the Division of Bacterial and Mycotic Diseases of the CDC. Information is available in English and Spanish. Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2018 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 Helicobacter pylori. 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 Helicobacter pylori. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Helicobacter pylori.

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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 Helicobacter pylori. 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 “Helicobacter pylori” (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 “Helicobacter pylori”. 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 “Helicobacter pylori” (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 “Helicobacter pylori” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

24

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •

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

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

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

25

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

Finding Medical Libraries 327 •

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/

Finding Medical Libraries 329 •

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/

•

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

•

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

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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/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Helicobacter pylori: •

Basic Guidelines for Helicobacter Pylori Helicobacter pylori gastritis (chronic gastritis) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000229.htm

•

Diagnostics and Tests for Helicobacter Pylori Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.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

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•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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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HELICOBACTER PYLORI DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimation: Adaptation of animals or plants to new climate. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Achlorhydria: A lack of hydrochloric acid in gastric juice despite stimulation of gastric secretion. [NIH] Actinobacillus: A genus of Pasteurellaceae described as gram-negative, nonsporeforming, nonmotile, facultative anaerobes. Most members are found both as pathogens and commensal organisms in the respiratory, alimentary, and genital tracts of animals. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a serine residue by a phosphodiester bond. Acyl groups are bound as thiol esters to the pantothenyl group. Acyl carrier protein is involved in every step of fatty acid synthesis by the cytoplasmic system. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different

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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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]

Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] 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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [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] 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 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] Aerophagia: A condition that occurs when a person swallows too much air. Causes gas and frequent belching. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element,

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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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from aging, a physiological process, and time factors which refers only to the passage of time. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] 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

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particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Sulfate: Sulfuric acid diammonium salt. It is used in fractionation of proteins. [NIH]

Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel,

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Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [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

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positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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] 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms.

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[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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Anti-Ulcer Agents: Various agents with different action mechanisms used to treat or ameliorate ulcers or irritation of the gastrointestinal tract. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antrectomy: An operation to remove the upper portion of the stomach, called the antrum. This operation helps reduce the amount of stomach acid. It is used when a person has complications from ulcers. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [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

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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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]

Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrial: Pertaining to an atrium. [EU]

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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] Atrophic Gastritis: Chronic irritation of the stomach lining. Causes the stomach lining and glands to wither away. [NIH] 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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] 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

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important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] 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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Beer: An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation. [NIH] Belching: Noisy release of gas from the stomach through the mouth. Also called burping. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-sheet: Two or more parallel or anti-parallel strands are arranged in rows. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH]

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Bewilderment: Impairment or loss of will power. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Reflux: Reflux of bile mainly into the upper digestive tract, but also into the pancreas. [NIH]

Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological 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] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [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

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technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bismuth Subsalicylate: A nonprescription medicine such as Pepto-Bismol. Used to treat diarrhea, heartburn, indigestion, and nausea. It is also part of the treatment for ulcers caused by the bacterium Helicobacter pylori (HELL-uh-koh-BAK-tur py-LOH-ree). [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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 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]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary

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permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breath Tests: Any tests done on exhaled air. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] 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] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

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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 enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefixime: A third-generation cephalosporin antibiotic that is stable to hydrolysis by betalactamases. [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]

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Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell 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 Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] 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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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

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the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholelithiasis: Presence or formation of gallstones. [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] 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]

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Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [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] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] 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

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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] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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] Colonic flora: The bacteria normally residing within the colon. [EU] Colorectal: Having to do with the colon or the rectum. [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] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] 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

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C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH]

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Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] 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

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homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] 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

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maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] 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] Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]

Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and

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distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] 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] 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] 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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] 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] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Diverticula: Plural form of diverticulum. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH]

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Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Costs: The amount that a health care institution or organization pays for its drugs. It is one component of the final price that is charged to the consumer (fees, pharmaceutical or prescription fees). [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug 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] 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]

Duodenitis: An irritation of the first part of the small intestine (duodenum). [NIH] Duodenogastric Reflux: Reflux of duodenal contents into the stomach. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service

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produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [NIH]

Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetic: An agent that causes vomiting. [EU] Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein syntheis in eucaryotic but not prokaryotic cells. [NIH] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

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Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

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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-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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiologic Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Eructation: The ejection of gas or air through the mouth from the stomach. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagectomy: An operation to remove a portion of the esophagus. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH]

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Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exfoliation: A falling off in scales or layers. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

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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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferrets: Semidomesticated variety of European polecat much used for hunting rodents and/or rabbits and as a laboratory animal. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flagellin: A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella. [NIH] Flagellum: A whiplike appendage of a cell. It can function either as an organ of locomotion or as a device for moving the fluid surrounding the cell. [NIH] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH]

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Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fucose: Deoxysugar. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH]

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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] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [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] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric atrophy: A condition in which the stomach muscles shrink and become weak. The digestive (peptic) glands may also shrink, resulting in a lack of digestive juices. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Fundus: The superior portion of the body of the stomach above the level of the cardiac notch. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastric Outlet Obstruction: The hindering of output from the stomach to the small intestine. The source varies: peptic ulcer, foreign bodies, aging, neoplasms, etc. [NIH] Gastric Resection: An operation to remove part or all of the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastritis, Atrophic: Chronic gastritis with mucosal atrophy. [NIH]

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Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] 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] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrooesophageal: Pertaining to the stomach and oesophagus, as the gastrooesophageal junction. [EU] Gastroscopy: Endoscopic examination, therapy, or surgery of the interior of the stomach. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH]

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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] Geriatric: Pertaining to the treatment of the aged. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH]

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Glycoprotein: A protein that has sugar molecules attached to it. [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] Glycosyltransferases: Enzymes that catalyze the transfer of glycosyl groups to an acceptor. Most often another carbohydrate molecule acts as an acceptor, but inorganic phosphate can also act as an acceptor, such as in the case of phosphorylases. Some of the enzymes in this group also catalyze hydrolysis, which can be regarded as transfer of a glycosyl group from the donor to water. Subclasses include the hexosyltransferases, pentosyltransferases, sialyltransferases, and those transferring other glycosyl groups. EC 2.4. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [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-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] 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] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] 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

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survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] 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] Haematemesis: The vomiting of blood. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Helicobacter pylori: A spiral bacterium active as a human gastric pathogen. It is a gramnegative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus Campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the microorganism should be included in the genus Helicobacter. It has been officially transferred to

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Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [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] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH]

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Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hexosyltransferases: Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-. [NIH] Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] 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] Homotypic: Adhesion between neutrophils. [NIH] 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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Hospital Costs: The expenses incurred by a hospital in providing care. The hospital costs attributed to a particular patient care episode include the direct costs plus an appropriate proportion of the overhead for administration, personnel, building maintenance, equipment,

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etc. Hospital costs are one of the factors which determine hospital charges (the price the hospital sets for its services). [NIH] Host: Any animal that receives a transplanted graft. [NIH] Houseflies: Flies of the species Musca domestica (family muscidae), which infest human habitations throughout the world and often act as carriers of pathogenic organisms. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenase: An enzyme found in bacteria. It catalyzes the reduction of ferredoxin and other substances in the presence of molecular hydrogen and is involved in the electron transport of bacterial photosynthesis. EC 1.18.99.1. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylamine: A colorless inorganic compound (HONH2) used in organic synthesis and as a reducing agent, due to its ability to donate nitric oxide. [NIH] Hyperemesis: Excessive vomiting. [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] Hypersecretion: Excessive secretion. [EU] 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]

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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] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Ice Cream: A frozen dairy food made from cream or butterfat, milk, sugar, and flavorings. Frozen custard and French-type ice creams also contain eggs. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [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-response: The production of antibodies or particular types of cytotoxic lymphoid cells on challenge with an antigen. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH]

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Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also

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called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]

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]

Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own

Dictionary 375

psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH]

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Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in 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] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Ipecac: A syrup made from the dried rhizomes of two different species, Cephaelis ipecacuanha and C. acuminata, belonging to the Rubiaciae family. They contain emetine, cephaeline, psychotrine and other isoquinolines. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone. [NIH]

Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isocitrate Lyase: A key enzyme in the glyoxylate cycle. It catalyzes the conversion of isocitrate to succinate and glyoxylate. EC 4.1.3.1. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal

Dictionary 377

layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] 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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH]

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Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [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] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligase Chain Reaction: A DNA amplification technique based upon the ligation of oligonucleotide probes. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH]

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Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] 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]

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Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] 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] Lymphoepithelioma: A type of cancer that begins in the tissues covering the nasopharynx (the upper part of the throat behind the nose). [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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 tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [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] 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]

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Maxillary Sinus: One of the paired paranasal sinuses, located in the body of the maxilla, communicating with the middle meatus of the nasal cavity. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight

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200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

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Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mode of Transmission: Hepatitis A [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] 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] Monotherapy: A therapy which uses only one drug. [EU] 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]

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Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mupirocin: A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing. [NIH] Muscidae: A family of the order Diptera with over 700 species. Important species that may be mechanical vectors of disease include Musca domesticus (houseflies), Musca autumnalis (face fly), Stomoxys calcitrans (stable fly), Haematobia irritans (horn fly) and Fannia spp. [NIH]

Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be

Dictionary 385

induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [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]

Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] 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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]

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Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogenase: An enzyme system that catalyzes the fixing of nitrogen in soil bacteria and blue-green algae (cyanobacteria). EC 1.18.6.1. [NIH] Nonulcer Dyspepsia: Constant pain or discomfort in the upper GI tract. Symptoms include burning, nausea, and bloating, but no ulcer. Possibly caused by muscle spasms. [NIH]

Dictionary 387

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] NSAIDs: Nonsteroidal anti-inflammatory drugs. A group of drugs that decrease fever, swelling, pain, and redness. [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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oesophagitis: Inflammation of the esophagus. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the

388

Helicobacter pylori

molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [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] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of

Dictionary 389

synthetic antibiotic agents. [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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU]

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Parietal Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] 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 Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatric Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentosyltransferases: Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another. (Dorland, 28th ed) EC 2.4.2. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU]

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Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforated Ulcer: An ulcer that breaks through the wall of the stomach or the duodenum. Causes stomach contents to leak into the abdominal cavity. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [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] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phagosomes:

Membrane-bound

cytoplasmic

vesicles

formed

by

invagination

of

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Helicobacter pylori

phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolsulfonphthalein: Red dye, pH indicator, and diagnostic aid for determination of renal function. It is used also for studies of the gastrointestinal and other systems. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphates: Inorganic salts of phosphoric acid. [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] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] 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]

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Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plant Diseases: Diseases of plants. [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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH]

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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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyp: A growth that protrudes from a mucous membrane. [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] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porins: Protein molecules situated in the outer membrane of gram-negative bacteria that, in dimeric or trimeric form, constitute a water-filled transmembrane channel allowing passage of ions and other small molecules. Porins are also found in bacterial cell walls, and in plant, fungal, mammalian and other vertebrate cell and mitochondrial membranes. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on

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the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] 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] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prescription Fees: The charge levied on the consumer for drugs or therapy prescribed under written order of a physician or other health professional. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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 Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] 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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase

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holoenzyme and determines the maximal rate of RNA synthesis. [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] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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 Folding: A rapid biochemical reaction involved in the formation of proteins. It

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begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]

Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] 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]

Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and

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editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary 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] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] 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] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Chimera: An organism whose body contains cell populations of different genotypes as a result of the transplantation of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells. [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

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substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [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. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Ranitidine Bismuth Citrate: Drug used to eradicate Helicobacter pylori. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] 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

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liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [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 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]

Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the

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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] Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retching: Dry vomiting. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour

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vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] 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] Retrosternal: Situated or occurring behind the sternum. [EU] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH]

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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] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [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] 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] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] 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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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 circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sialyltransferases: A group of enzymes with the general formula CMP-Nacetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of Nacetylneuraminic acid from CMP-N-acetylneuraminic acid to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. EC 2.4.99.-. [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] Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter)

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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] Simethicone: A mixture of dimethyl polysiloxanes and silica gel used as an antiflatulent. Without the addition of silica gel (dimethicone), it is used as an ointment base ingredient and skin protectant. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [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] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [NIH] 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 Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [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] 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]

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Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [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] 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] 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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Standardize: To compare with or conform to a standard; to establish standards. [EU] 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

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animals. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] 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] Sternum: Breast bone. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomach Ulcer: An open sore in the lining of the stomach. Also called gastric ulcer. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stool test: A test to check for hidden blood in the bowel movement. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] 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] 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]

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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] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] 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] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [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] Symbiosis: The living together of organisms of different species. [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] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] 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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachykinins: A family of biologically active peptides sharing a common conserved Cterminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched

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aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [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] Tetracycline Resistance: Nonsusceptibility of a microbe (usually a bacterium) to the action of tetracycline, which binds to the 30S ribosomal subunit and prevents the normal binding of aminoacyl-tRNA. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators

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of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thylakoids: Membranous cisternae of the chloroplast containing photosynthetic pigments, reaction centers, and the electron-transport chain. Each thylakoid consists of a flattened sac of membrane enclosing a narrow intra-thylakoid space (Lackie and Dow, Dictionary of Cell Biology, 2nd ed). Individual thylakoids are interconnected and tend to stack to form aggregates called grana. They are found in cyanobacteria and all plants. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Factors: Elements of limited time intervals, contributing to particular results or situations. [NIH] Tinidazole: A nitroimidazole antitrichomonal agent effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia infections. [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] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] 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] Tonsil: A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the pharynx situated on each side of the fauces, between the anterior and posterior pillars of the soft palate. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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]

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Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Training Support: Financial support for training including both student stipends and loans and training grants to institutions. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is 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] Translating: Conversion from one language to another language. [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] Translocate: 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]

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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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triple-Therapy: A combination of three medicines used to treat Helicobacter pylori infection and ulcers. Drugs that stop the body from making acid are often added to relieve symptoms. [NIH] 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] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH]

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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] Ulcerogenic: Causing ulceration; leading to the production of ulcers. [EU] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

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] Urea Breath Test: A test used to detect Helicobacter pylori infection. The test measures breath samples for urease, an enzyme H. pylori makes. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. [NIH]

414

Helicobacter pylori

Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [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] 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] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] 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] 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] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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

Dictionary 415

kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] 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] World Health: The concept pertaining to the health status of inhabitants of the world. [NIH] World Health Organization: A specialized agency of the United Nations designed as a coordinating authority on international health work; its aim is to promote the attainment of the highest possible level of health by all peoples. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] 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]

417

INDEX A Abdomen, 333, 344, 360, 376, 379, 389, 391, 406, 407, 415 Abdominal, 8, 10, 12, 43, 187, 257, 333, 355, 365, 376, 389, 391, 413 Abdominal Pain, 8, 10, 12, 187, 257, 333, 365, 376, 413 Aberrant, 18, 89, 108, 112, 115, 333 Ablation, 88, 333 Acatalasia, 333, 346 Acceptor, 144, 333, 367, 379, 389, 404, 411 Acclimation, 271, 333 Acetone, 64, 333, 377 Acetylcholine, 333, 349, 386 Acetylcysteine, 222, 333 Achlorhydria, 92, 333 Actinobacillus, 225, 333 Activities of Daily Living, 8, 333 Acute renal, 333, 369 Acyl, 68, 333 Acyl Carrier Protein, 68, 333 Adaptability, 333, 347 Adaptation, 21, 75, 111, 147, 157, 333, 334, 384 Adenine, 334, 398 Adenomatous Polyposis Coli, 185, 334 Adenosine, 199, 276, 334, 392 Adenosine Triphosphate, 276, 334, 392 Adenylate Cyclase, 334, 348 Adhesions, 244, 334 Adjustment, 334 Adjuvant, 13, 30, 68, 84, 112, 121, 161, 334 Adoptive Transfer, 108, 121, 125, 133, 334 Adrenal Medulla, 334, 346, 360, 387 Adrenergic, 334, 357, 360, 408 Adverse Effect, 41, 42, 275, 334, 404 Aerobic, 334, 383, 385, 389 Aerophagia, 257, 334 Aetiology, 257, 334 Afferent, 117, 334, 375 Affinity, 122, 260, 261, 268, 334, 335, 340, 405 Agar, 13, 51, 126, 152, 335, 353, 373, 393 Age Factors, 51, 335 Aggressiveness, 268, 335 Agonist, 335, 345, 357 Alanine, 74, 197, 335 Algorithms, 335, 344

Alkaline, 74, 91, 117, 335, 336, 345 Alkaline Phosphatase, 74, 335 Alkaloid, 335, 345, 358 Alleles, 71, 75, 85, 95, 119, 143, 160, 162, 165, 168, 335 Allergen, 335, 404 Allogeneic, 206, 335, 367 Allogeneic bone marrow transplantation, 206, 335 Alpha Particles, 335, 398 Alpha-1, 336, 353 Alternative medicine, 295, 336 Alum, 84, 121, 336 Aluminum, 336, 408 Amebiasis, 336, 382 Ameliorating, 248, 336 Amine, 336, 370 Amino Acid Sequence, 80, 82, 239, 252, 259, 277, 336, 338, 365 Amino Acids, 119, 153, 272, 336, 360, 365, 386, 391, 394, 397, 402, 404, 408, 411, 413 Ammonium Sulfate, 270, 336 Ampicillin, 166, 229, 336 Amplification, 81, 88, 126, 260, 261, 336, 378 Ampulla, 336, 359 Amyloid, 80, 336 Anaemia, 178, 337, 381 Anaerobic, 337, 403, 406 Anaesthesia, 337, 374 Anal, 6, 178, 337, 362 Analgesic, 337, 372, 378 Analog, 39, 74, 337 Analogous, 337, 357, 411 Analytes, 314, 337 Anaphylatoxins, 337, 351 Anaplasia, 337 Anatomical, 337, 341, 356, 358, 373, 403 Anemia, 58, 206, 311, 320, 337, 363 Anesthesia, 337 Anesthetics, 337, 360 Aneurysm, 337, 339, 414 Angiogenesis, 252, 277, 337, 380 Angiotensin converting enzyme inhibitor, 105, 337 Animal model, 13, 21, 30, 52, 66, 72, 82, 86, 92, 93, 98, 231, 253, 266, 337 Anions, 337, 376, 408

418

Helicobacter pylori

Anisotropy, 338, 363 Annealing, 338, 378, 394 Anomalies, 161, 338, 384 Anorexia, 8, 338, 365, 413 Anticoagulant, 338, 396 Antigen-Antibody Complex, 338, 351 Antigen-presenting cell, 196, 338 Anti-infective, 70, 338, 371 Anti-Inflammatory Agents, 277, 338, 340 Antineoplastic, 275, 338 Antineoplastic Agents, 275, 338 Antioxidant, 111, 127, 222, 339, 340, 389 Antiseptic, 333, 339 Anti-Ulcer Agents, 248, 339 Antiviral, 333, 339, 375 Antrectomy, 15, 339 Anus, 337, 339, 344, 362 Anxiety, 277, 339 Aorta, 339, 414 Aortic Aneurysm, 133, 191, 339 Aphasia, 210, 339 Apolipoproteins, 339, 379 Apoptosis, 21, 30, 73, 83, 93, 99, 100, 103, 110, 119, 138, 167, 183, 200, 210, 271, 339 Approximate, 94, 250, 339 Aqueous, 192, 269, 339, 342, 349, 354, 358, 371, 377 Aqueous humor, 192, 339, 349 Arachidonate 12-Lipoxygenase, 339, 379 Arachidonate 15-Lipoxygenase, 339, 379 Arachidonate Lipoxygenases, 339, 379 Arachidonic Acid, 275, 339, 340, 378, 396 Arginase, 89, 97, 142, 145, 340 Arginine, 89, 337, 340, 386, 388, 398 Aromatic, 340, 392, 408 Arterial, 340, 349, 352, 371, 397, 408 Arteries, 121, 339, 340, 344, 352, 379, 382, 385, 398, 409 Arterioles, 340, 344, 345, 382 Arteriovenous, 340, 382 Articular, 340, 388 Ascorbic Acid, 206, 222, 340 Aseptic, 340, 388 Aspirin, 8, 9, 17, 34, 35, 65, 91, 118, 122, 292, 294, 319, 340 Astrocytes, 272, 340, 383 Ataxia, 310, 311, 340, 409 Atherogenic, 121, 340 Atrial, 340, 352, 412 Atrioventricular, 341, 352 Atrium, 340, 341, 352, 412, 414

Atrophic Gastritis, 16, 17, 39, 42, 48, 53, 60, 77, 88, 93, 96, 103, 157, 184, 258, 287, 341 Atrophy, 16, 17, 20, 29, 31, 36, 39, 42, 60, 61, 93, 170, 242, 296, 310, 341, 364 Attenuated, 30, 94, 112, 127, 262, 341, 356 Attenuation, 70, 341 Autacoids, 341, 374 Autodigestion, 341, 389 Autoimmune disease, 37, 38, 341 Autoimmunity, 199, 341 Autolysis, 139, 163, 341 Azithromycin, 13, 293, 341 B Bacillus, 234, 238, 239, 248, 341, 353 Bacteremia, 341, 403 Bacterial Adhesion, 30, 261, 341 Bacterial Infections, 40, 228, 240, 243, 258, 270, 273, 274, 276, 314, 341, 347, 367, 401 Bacterial Physiology, 122, 334, 341 Bacterial toxin, 244, 341 Bactericidal, 49, 127, 145, 163, 166, 217, 341, 361 Bacteriophage, 341, 393, 403, 411, 414 Bacteriostatic, 342, 360 Basal Ganglia, 340, 342 Basal Ganglia Diseases, 340, 342 Base, 31, 55, 69, 95, 104, 110, 274, 334, 342, 353, 355, 363, 365, 376, 394, 405, 412, 413 Basement Membrane, 342, 361 Basophil, 342, 370 Beer, 230, 342 Belching, 334, 342 Benign, 15, 136, 342, 362, 368, 377, 385, 399 Beta carotene, 78, 342 Beta Rays, 342, 358 Beta-Galactosidase, 74, 342 Beta-Lactamases, 342, 346 Beta-pleated, 336, 342 Beta-sheet, 80, 342 Beta-Thromboglobulin, 342, 375 Bewilderment, 343, 351 Bile, 37, 61, 343, 364, 365, 369, 371, 379, 408 Bile Acids, 343, 365 Bile Acids and Salts, 343 Bile Ducts, 343, 364 Bile Reflux, 61, 343 Biliary, 37, 147, 343, 369, 389 Biliary Tract, 37, 343, 389 Bioassay, 80, 343

Index 419

Biochemical, 69, 85, 109, 150, 208, 228, 247, 257, 335, 343, 363, 365, 367, 377, 388, 396, 409 Biochemical reactions, 343, 409 Biogenesis, 119, 343 Biological response modifier, 343, 375 Biological therapy, 343, 368 Biological Transport, 343, 355 Biopolymers, 74, 343 Biopsy specimen, 18, 29, 129, 135, 139, 155, 182, 199, 239, 243, 249, 279, 343 Biosynthesis, 64, 68, 96, 106, 122, 153, 231, 250, 253, 340, 343, 388, 404 Biotechnology, 80, 123, 167, 217, 220, 295, 307, 309, 310, 311, 343 Bioterrorism, 114, 344 Biotransformation, 344 Bismuth Subsalicylate, 56, 229, 300, 344 Bivalent, 112, 344 Bladder, 69, 344, 363, 373, 396, 413 Bloating, 257, 344, 373, 376, 386 Blood Coagulation, 344, 345, 402, 409 Blood pressure, 181, 344, 346, 348, 371, 383, 398, 405 Blot, 83, 147, 274, 344, 372, 388 Blotting, Western, 344, 372 Body Fluids, 344, 357, 405 Bone Marrow, 121, 344, 372, 380, 383, 405, 407 Bone Marrow Transplantation, 344 Bowel, 39, 111, 246, 316, 337, 344, 356, 359, 374, 376, 377, 391, 407, 413 Bowel Movement, 344, 356, 407 Bradykinin, 344, 386 Branch, 329, 345, 365, 381, 390, 397, 406, 408, 409 Breakdown, 345, 355, 364 Breath Tests, 19, 22, 23, 25, 57, 68, 286, 345 Broad-spectrum, 336, 345, 387, 402 Bronchi, 345, 360, 411 Bronchial, 345, 370 Bronchospasm, 278, 345 Buffers, 110, 117, 345 C Calcium, 9, 345, 349, 350, 380, 397, 405 Capillary, 269, 344, 345, 414 Capsaicin, 117, 345 Capsules, 216, 345, 359 Carbachol, 91, 345 Carbohydrate, 143, 345, 367, 394, 404 Carbon Dioxide, 52, 63, 145, 230, 231, 253, 257, 280, 345, 353, 354, 362, 364, 401, 414

Carboxy, 74, 238, 345 Carboxy-terminal, 74, 345 Carcinogen, 73, 77, 92, 103, 117, 268, 345, 382, 384 Carcinogenesis, 8, 69, 77, 85, 93, 99, 103, 106, 116, 175, 178, 185, 200, 345, 348 Carcinogenic, 74, 100, 103, 245, 259, 345, 374, 388, 395 Carcinoma, 26, 93, 98, 106, 111, 127, 132, 171, 191, 207, 255, 262, 268, 285, 345 Cardia, 25, 29, 31, 53, 61, 183, 346 Cardiac, 59, 346, 352, 358, 360, 364, 385 Cardiovascular, 9, 37, 65, 252, 277, 278, 346, 378, 409 Cardiovascular disease, 9, 277, 278, 346 Carotene, 220, 342, 346, 401 Carotenoids, 69, 342, 346 Case report, 346, 350 Case series, 22, 346, 350 Case-Control Studies, 76, 97, 346 Catalase, 130, 239, 265, 333, 346 Cataract, 81, 346 Catecholamine, 346, 357 Cathode, 342, 346, 358 Cations, 346, 376 Causal, 50, 53, 92, 319, 346 Cause of Death, 8, 61, 98, 265, 346 Cefixime, 13, 346 Cell Adhesion, 272, 347, 375 Cell Adhesion Molecules, 272, 347 Cell Cycle, 21, 347 Cell Death, 66, 86, 103, 110, 115, 131, 235, 339, 347, 385 Cell Differentiation, 112, 347, 405 Cell Division, 116, 155, 310, 341, 347, 367, 381, 382, 383, 393, 396, 403 Cell Fusion, 213, 347 Cell Lineage, 81, 347 Cell membrane, 74, 91, 230, 235, 343, 347, 355, 361, 392 Cell proliferation, 17, 93, 99, 115, 155, 208, 347, 405 Cell Respiration, 347, 383, 389, 401 Cell Size, 347, 363 Cell Survival, 112, 347, 368 Cellulose, 347, 364, 393 Central Nervous System, 252, 272, 277, 333, 335, 347, 366, 368, 378, 409 Central Nervous System Infections, 347, 368 Cerebellar, 340, 347, 400

420

Helicobacter pylori

Cerebral, 340, 342, 347, 348, 360, 361, 375, 390, 406 Cerebrovascular, 342, 346, 347, 409 Cerebrum, 347, 412 Character, 348, 354 Chemokines, 115, 348 Chemoprevention, 69, 77, 264, 348 Chemopreventive, 264, 265, 348 Chemoreceptor, 348, 376 Chemotactic Factors, 348, 351 Chemotaxis, 67, 117, 120, 144, 203, 348 Chemotherapy, 180, 198, 200, 207, 248, 348 Chlorine, 137, 249, 280, 348, 372 Chlorophyll, 348, 353, 359, 364 Chloroplasts, 109, 348, 353 Cholecystectomy, 105, 348 Cholelithiasis, 105, 348 Cholera, 152, 262, 348, 414 Cholera Toxin, 152, 262, 348 Cholesterol, 105, 179, 315, 343, 348, 349, 352, 364, 379 Cholesterol Esters, 349, 379 Cholinergic, 345, 349 Chromatin, 235, 339, 349, 360 Chromosomal, 76, 129, 144, 147, 152, 336, 349, 365, 393 Chromosome, 93, 262, 349, 368, 378, 403, 411 Chronic renal, 169, 349, 394, 413 Chylomicrons, 349, 379 Ciliary, 339, 349, 384 Ciliary processes, 339, 349 Cimetidine, 229, 278, 349 Ciprofloxacin, 13, 155, 349 CIS, 81, 222, 349, 401 Citric Acid, 11, 126, 349 Citrus, 340, 349 Clamp, 81, 349 Clathrin, 349, 350, 359 Clinical Medicine, 349, 395 Clinical study, 8, 349 Clinical trial, 38, 54, 55, 63, 69, 153, 307, 350, 351, 352, 384, 390, 397, 399 Cloning, 68, 87, 106, 130, 143, 152, 158, 174, 217, 220, 231, 343, 350, 374, 378 Coagulation, 101, 121, 344, 350, 369, 410 Coated Vesicles, 349, 350, 359 Coenzyme, 105, 275, 340, 350, 363 Cofactor, 103, 106, 264, 350, 386, 397, 409 Colitis, 72, 350, 376 Collagen, 342, 350, 361, 362, 380, 393, 395 Colloidal, 46, 229, 350, 358

Colonic flora, 52, 350 Colorectal, 87, 350 Combination Therapy, 14, 61, 121, 139, 245, 259, 350 Combinatorial, 70, 350 Commensal, 75, 333, 350 Complement, 95, 120, 337, 350, 365, 375, 404 Complete remission, 183, 351, 401 Complete response, 351 Computational Biology, 307, 309, 351 Conduction, 73, 351 Cone, 109, 351 Confounding, 101, 351 Confusion, 17, 62, 351, 356, 413 Conjugated, 343, 351, 353 Connective Tissue, 340, 344, 350, 351, 362, 402 Consciousness, 337, 351, 355, 356, 369 Constipation, 351, 376 Consumption, 216, 351, 355, 365, 389 Contamination, 67, 267, 351 Contraindications, ii, 351 Control group, 58, 351 Controlled study, 198, 352 Conventional therapy, 352 Conventional treatment, 231, 352 Coordination, 79, 352 Cor, 257, 352 Cornea, 339, 352 Coronary, 9, 38, 69, 101, 207, 294, 346, 352, 382, 385 Coronary heart disease, 38, 101, 207, 294, 346, 352 Coronary Thrombosis, 352, 382, 385 Corpus, 4, 12, 16, 25, 39, 44, 49, 59, 127, 161, 242, 268, 352 Cortex, 340, 352, 361, 375, 400 Cost Savings, 54, 352 Cranial, 352, 368, 389, 391, 413 Craniocerebral Trauma, 342, 352, 368, 409 Crossing-over, 352, 399 Crowding, 264, 353 Cryptosporidiosis, 341, 353 Crystallization, 120, 353 Cues, 117, 118, 353 Culture Media, 335, 353 Cultured cells, 84, 353 Curative, 353, 409 Cutaneous, 207, 353 Cyanide, 353, 382 Cyanobacteria, 353, 386, 410

Index 421

Cyclic, 13, 277, 334, 353, 368, 386, 396 Cyclodextrins, 142, 353 Cysteine, 81, 104, 333, 348, 353, 408 Cystine, 353 Cytochrome, 106, 173, 194, 222, 349, 353, 354, 401 Cytochrome b, 354, 401 Cytokine, 66, 83, 89, 90, 92, 98, 100, 108, 112, 113, 185, 186, 354, 375 Cytomegalovirus, 101, 171, 354 Cytoplasm, 112, 339, 347, 348, 354, 358, 360, 367, 383, 402, 413 Cytoplasmic Vesicles, 354, 391 Cytoskeleton, 354, 375 Cytotoxic, 82, 168, 264, 345, 354, 372, 399, 405 Cytotoxicity, 152, 208, 354 Cytotoxins, 290, 354 D Databases, Bibliographic, 307, 354 De novo, 4, 75, 354 Deamination, 354, 413 Decarboxylation, 64, 354, 370, 388, 398 Decision Making, 20, 354 Defecation, 18, 354 Defense Mechanisms, 104, 111, 354, 375 Degenerative, 104, 354, 369, 388, 402 Dehydration, 348, 354 Deletion, 82, 150, 176, 339, 354 Delivery of Health Care, 354, 368 Dementia, 278, 355 Denaturation, 355, 378, 394 Dendrites, 355, 386 Density, 47, 49, 163, 176, 179, 193, 232, 355, 363, 379, 388, 406 Dental Caries, 249, 355 Dental Plaque, 138, 189, 355 Depolarization, 355, 405 Dermal, 355, 378 Deuterium, 355, 371 Developed Countries, 8, 24, 33, 53, 173, 263, 264, 270, 296, 355 Developing Countries, 28, 53, 98, 100, 228, 231, 243, 255, 263, 264, 270, 285, 296, 355 Diagnostic procedure, 68, 227, 295, 355, 404 Diaphragm, 355, 370 Diarrhea, 7, 9, 14, 23, 245, 259, 269, 319, 336, 344, 353, 355, 358, 376 Diarrhoea, 355, 365 Diastolic, 355, 371 Diathermy, 355, 383

Diffusion, 117, 343, 355, 356, 373, 374, 386 Digestion, 24, 48, 266, 335, 343, 344, 355, 357, 373, 376, 379, 390, 407 Digestive system, 233, 356, 365 Digestive tract, 72, 343, 356, 405 Dihydrotestosterone, 356, 400 Dilatation, 337, 356, 395, 414 Dilatation, Pathologic, 356, 414 Dilation, 15, 17, 47, 344, 356, 414 Dilution, 13, 356 Dimerization, 119, 356 Dimethyl, 356, 405 Diploid, 356, 393 Direct, iii, 24, 27, 30, 37, 56, 67, 80, 94, 98, 103, 115, 132, 135, 151, 232, 236, 237, 299, 349, 356, 357, 366, 370, 400 Disease Progression, 121, 249, 356 Disinfection, 244, 245, 258, 259, 356 Disorientation, 351, 356 Dissection, 102, 356 Dissociation, 335, 356, 376 Distal, 43, 57, 64, 93, 119, 356, 365, 397 Diverticula, 174, 356 Diverticulum, 356 Dopa, 222, 356, 378 Dopamine, 271, 357, 378, 383, 392 Drug Costs, 62, 357 Drug Design, 107, 357 Drug Interactions, 300, 301, 357 Drug Resistance, 10, 41, 75, 87, 294, 357 Drug Tolerance, 357, 410 Duct, 336, 357, 403 Duodenitis, 229, 256, 357 Duodenogastric Reflux, 205, 357 Dyes, 336, 357, 363, 386 Dysphagia, 58, 357 Dysplasia, 17, 53, 78, 96, 273, 311, 357 Dystrophy, 310, 357 E Ecosystem, 118, 357 Effector, 333, 350, 357, 386 Egg Yolk, 126, 152, 166, 235, 236, 237, 270, 358 Electrocoagulation, 350, 358 Electrolyte, 358, 405, 413 Electrons, 104, 339, 342, 346, 358, 376, 389, 398, 399 Electrophoresis, 94, 130, 147, 187, 263, 358, 373 Elementary Particles, 358, 386, 397 Ellagic Acid, 220, 358 Embolus, 358, 374

422

Helicobacter pylori

Embryo, 347, 358, 374 Emesis, 18, 252, 277, 278, 358 Emetic, 18, 358, 376 Emetine, 358, 376 Emodin, 216, 358 Empirical, 14, 25, 55, 358 Emulsions, 335, 358 Enamel, 355, 358 Encapsulated, 232, 358 Endemic, 77, 100, 348, 359, 406 Endoscope, 232, 359 Endoscopic, 10, 13, 17, 22, 36, 37, 38, 49, 57, 59, 63, 121, 133, 135, 174, 183, 212, 255, 359, 365 Endosomes, 99, 359 Endothelial cell, 359, 375, 409 Endothelium, 275, 276, 359, 386, 393 Endothelium, Lymphatic, 359 Endothelium, Vascular, 359 Endothelium-derived, 275, 276, 359, 386 Endotoxic, 94, 359 Endotoxin, 68, 106, 359, 412 End-stage renal, 349, 359, 394 Enhancer, 359, 401 Enteric bacteria, 232, 256, 359 Enteric-coated, 251, 359 Enteritis, 269, 359 Enterocolitis, 359 Environmental Exposure, 359, 388 Environmental Health, 306, 308, 359 Enzymatic, 68, 345, 346, 351, 355, 360, 370, 394, 401 Enzyme-Linked Immunosorbent Assay, 32, 132, 156, 360 Eosinophils, 360, 367, 377 Epidemiologic Factors, 290, 360 Epidemiological, 9, 24, 50, 85, 103, 219, 228, 242, 360 Epidermal, 360, 376, 378, 381 Epidermis, 360, 376, 378, 398 Epigastric, 43, 56, 193, 241, 360, 389 Epinephrine, 121, 334, 357, 360, 387, 412 Eructation, 233, 268, 360 Erythema, 360, 408 Erythrocytes, 337, 344, 360, 400, 404 Erythromycin, 13, 154, 272, 341, 349, 360 Esophageal, 43, 76, 87, 116, 179, 186, 221, 258, 265, 291, 292, 360, 365 Esophagectomy, 186, 360 Esophagitis, 39, 49, 59, 60, 107, 116, 161, 219, 360, 365, 408 Essential Tremor, 310, 361

Ethanol, 361, 362 Ether, 277, 361 Eukaryotic Cells, 73, 119, 142, 361, 373, 387, 388 Evacuation, 351, 361, 364, 377 Evoke, 361, 407 Excitation, 348, 361, 363 Exfoliation, 192, 361 Exocytosis, 361, 370 Exogenous, 72, 142, 344, 361 Expiration, 361, 401 Extracellular, 67, 86, 108, 140, 144, 150, 163, 272, 336, 340, 351, 361, 362, 375, 380, 405 Extracellular Matrix, 86, 144, 351, 361, 362, 375, 380 Extracellular Matrix Proteins, 144, 361, 380 Extracellular Space, 361 Extraction, 80, 361 Extrapyramidal, 357, 361 F Faecal, 132, 355, 361 Failure to Thrive, 91, 361 Familial polyposis, 293, 361 Family Planning, 307, 362 Fat, 76, 269, 340, 342, 343, 344, 346, 352, 358, 362, 377, 379, 402, 405 Fatty acids, 163, 217, 362, 379, 396, 410 Feces, 9, 110, 138, 151, 351, 361, 362, 407 Fermentation, 261, 342, 362, 403 Ferrets, 30, 362 Fibrinogen, 101, 362, 393, 409 Fibroblasts, 362, 375 Fibroid, 185, 362, 377 Fibrosis, 311, 362, 403 Fistula, 362, 365 Fixation, 362, 404 Flagellin, 131, 148, 153, 362 Flagellum, 125, 250, 362 Flatulence, 257, 362 Flatus, 363, 364 Flexor, 363, 378 Flow Cytometry, 83, 363 Fluorescence, 65, 70, 75, 86, 91, 104, 140, 145, 147, 184, 363 Fluorescence Polarization, 75, 363 Fluorescent Dyes, 363 Folate, 363 Fold, 25, 61, 80, 363 Folic Acid, 272, 363 Foramen, 363, 381, 391

Index 423

Forearm, 344, 363 Fractionation, 102, 336, 363 Frameshift, 363, 412 Frameshift Mutation, 363, 412 Fucose, 217, 363 Fundus, 91, 363 Fungi, 246, 364, 367, 376, 382, 406, 415 Fungus, 19, 364 G Galactosides, 342, 364 Gallbladder, 333, 343, 348, 356, 363, 364, 365 Gallstones, 343, 348, 364 Gamma Rays, 364, 384, 398, 399 Gas, 52, 234, 256, 334, 336, 342, 345, 348, 355, 360, 362, 363, 364, 371, 373, 376, 384, 386, 388, 408, 414 Gas exchange, 364, 414 Gastrectomy, 17, 364 Gastric atrophy, 44, 92, 100, 220, 364 Gastric Emptying, 11, 51, 179, 364 Gastric Fundus, 91, 364 Gastric Juices, 110, 243, 364, 390 Gastric Mucosa, 13, 21, 22, 35, 58, 63, 66, 78, 81, 83, 86, 89, 91, 94, 95, 96, 97, 98, 103, 110, 111, 114, 115, 118, 119, 122, 127, 134, 140, 144, 159, 177, 181, 187, 193, 196, 203, 208, 209, 218, 221, 222, 231, 232, 234, 236, 237, 240, 243, 248, 251, 253, 256, 260, 261, 264, 267, 274, 279, 280, 285, 287, 289, 294, 296, 364, 376 Gastric Outlet Obstruction, 15, 46, 286, 364 Gastric Resection, 17, 364 Gastrin, 49, 91, 187, 242, 349, 364, 370 Gastritis, Atrophic, 93, 364 Gastroenteritis, 114, 258, 365, 403 Gastroenterologist, 13, 320, 365 Gastrointestinal Hemorrhage, 39, 365 Gastrooesophageal, 257, 365 Gastroscopy, 242, 314, 365 Gene Expression, 66, 70, 81, 83, 88, 94, 96, 107, 118, 127, 132, 134, 135, 141, 157, 158, 163, 193, 250, 311, 365 General practitioner, 68, 365 Genetic Code, 365, 387 Genetic Engineering, 343, 350, 365 Genetic Techniques, 122, 365 Genetic testing, 365, 394 Genetics, 21, 61, 70, 87, 95, 152, 187, 284, 296, 365, 366 Genital, 107, 333, 349, 366

Genitourinary, 366, 409 Genomics, 83, 96, 131, 366 Genotype, 71, 95, 97, 110, 115, 125, 130, 146, 194, 366, 392 Geriatric, 8, 35, 318, 366 Giardiasis, 366, 382 Ginseng, 220, 366 Gland, 84, 185, 245, 259, 334, 366, 389, 396, 403, 407, 410 Glomerular, 108, 366 Glomeruli, 366 Glomerulonephritis, 108, 366 Glomerulus, 366, 385 Glucans, 353, 366 Glucose, 64, 261, 293, 310, 340, 347, 353, 366, 369, 375 Glucuronic Acid, 366, 369 Glutamate, 104, 122, 366 Glutamic Acid, 363, 366, 395 Glutamine, 122, 143, 366 Glutathione Peroxidase, 366, 403 Glycine, 343, 366, 404 Glycoprotein, 362, 367, 384, 404, 409, 412 Glycosidic, 367, 388 Glycosylation, 108, 367 Glycosyltransferases, 68, 367 Governing Board, 367, 395 Grade, 17, 27, 85, 140, 181, 191, 292, 367 Grading, 205, 367 Graft, 206, 367, 371, 373 Graft Rejection, 367, 373 Gram-negative, 64, 68, 106, 122, 164, 225, 228, 231, 236, 237, 238, 239, 243, 244, 248, 250, 253, 255, 258, 261, 262, 263, 274, 279, 333, 353, 359, 367, 368, 387, 394, 403, 414 Gram-Negative Bacteria, 164, 243, 262, 353, 359, 367, 394 Gram-positive, 367, 384, 385, 387, 406, 407 Granule, 67, 367, 402 Granulocytes, 342, 367, 405, 415 Granulomatous Disease, Chronic, 367, 401 Grasses, 363, 367 Growth factors, 83, 86, 272, 367 Guanylate Cyclase, 368, 386 H Habitat, 368, 385, 386 Haematemesis, 358, 368 Hair follicles, 368, 415 Halitosis, 56, 292, 368 Haploid, 368, 393 Haptens, 335, 368

424

Helicobacter pylori

Headache, 319, 368 Headache Disorders, 368 Health Care Costs, 41, 65, 286, 368 Health Expenditures, 368 Health Status, 368, 415 Heart attack, 346, 368 Heartburn, 7, 10, 36, 38, 43, 48, 54, 56, 58, 60, 268, 286, 317, 344, 368, 370, 373 Heme, 150, 353, 354, 369 Hemochromatosis, 76, 369 Hemoglobin, 337, 360, 369 Hemoglobinuria, 310, 369 Hemolytic, 130, 144, 220, 369 Hemorrhage, 5, 47, 121, 221, 286, 352, 358, 368, 369, 398, 407 Hemostasis, 101, 121, 369, 375 Heparin, 180, 271, 369, 393 Hepatic, 24, 358, 369, 379 Hepatic Encephalopathy, 24, 369 Hepatitis, 101, 235, 369, 383 Hepatobiliary, 39, 369 Hepatocytes, 369 Hereditary, 295, 369, 391, 402 Heredity, 365, 366, 369 Heritability, 16, 369 Hernia, 49, 370 Herpes, 101, 370 Herpes Zoster, 370 Heterodimers, 370, 375 Heterogeneity, 146, 335, 370 Heterotrophic, 364, 370 Hexosyltransferases, 367, 370 Hiatal Hernia, 49, 370 Histamine, 91, 105, 195, 218, 248, 278, 337, 349, 370, 399 Histamine Release, 218, 337, 370 Histidine, 118, 120, 122, 141, 144, 158, 266, 370 Histology, 7, 11, 12, 18, 19, 20, 22, 24, 29, 32, 36, 39, 49, 255, 286, 370, 389 Homeostasis, 91, 235, 370 Homologous, 162, 271, 335, 344, 353, 370, 384, 403, 404, 408, 411 Homotypic, 102, 191, 370 Hormonal, 341, 370 Hormone, 257, 343, 360, 364, 370, 375, 381, 402, 404, 406, 409, 410 Horseradish Peroxidase, 360, 370 Hospital Charges, 370, 371 Hospital Costs, 122, 370 Houseflies, 9, 146, 167, 371, 384 Humoral, 98, 108, 112, 148, 293, 367, 371

Humour, 371 Hybrid, 82, 85, 254, 371, 388 Hybridization, 64, 67, 83, 134, 147, 156, 159, 165, 260, 261, 347, 371, 388 Hybridoma, 108, 371 Hydrochloric Acid, 333, 371, 390 Hydrogen Peroxide, 346, 366, 371, 379, 408 Hydrogenase, 106, 371 Hydrolysis, 50, 122, 340, 342, 344, 346, 367, 371, 392, 394, 397 Hydrophobic, 81, 119, 371, 379 Hydroxylamine, 75, 371 Hyperemesis, 207, 371 Hyperplasia, 17, 42, 371, 378 Hypersecretion, 36, 44, 233, 371 Hypersensitivity, 20, 98, 153, 335, 371, 378, 402, 404 Hypertension, 181, 346, 368, 371, 413 Hypertrophy, 352, 371, 372, 412 Hypochlorous Acid, 280, 372 Hypothalamic, 257, 372 Hypothalamus, 372, 406 I Ibuprofen, 319, 372 Ice Cream, 269, 270, 372 Id, 224, 310, 315, 320, 321, 322, 328, 330, 372 Idiopathic, 37, 44, 180, 190, 199, 372 Ileum, 233, 258, 372, 376 Imidazole, 370, 372, 399 Immune adjuvant, 336, 372 Immune Sera, 372 Immune-response, 112, 372 Immunization, 30, 73, 84, 108, 119, 121, 148, 230, 262, 269, 288, 334, 372, 373, 395, 404 Immunoassay, 19, 157, 260, 268, 360, 372 Immunoblotting, 135, 261, 372 Immunochemistry, 18, 372 Immunodeficiency, 135, 310, 372 Immunodiffusion, 335, 373 Immunoelectrophoresis, 335, 373 Immunofluorescence, 102, 373 Immunogenic, 107, 112, 239, 240, 373 Immunoglobulin, 34, 135, 139, 146, 148, 151, 156, 162, 166, 177, 267, 273, 338, 373, 383, 404 Immunohistochemistry, 17, 18, 83, 97, 373 Immunologic, 77, 99, 334, 348, 372, 373, 399 Immunosuppressive, 105, 192, 373

Index 425

Immunosuppressive therapy, 373 Immunotherapy, 172, 334, 343, 373 Impairment, 21, 340, 343, 373, 381 Impotence, 115, 373 In situ, 57, 78, 83, 97, 113, 184, 373 In Situ Hybridization, 83, 97, 131, 134, 159, 184, 373 In vitro, 13, 21, 30, 51, 64, 70, 74, 78, 80, 81, 82, 83, 86, 89, 92, 93, 96, 99, 112, 113, 115, 120, 133, 137, 192, 193, 197, 200, 217, 219, 220, 257, 264, 347, 373, 394, 402, 404, 410 Incision, 373, 376 Incompetence, 365, 373 Incontinence, 252, 277, 373 Incubated, 94, 373 Incubation, 126, 240, 373 Indicative, 282, 373, 390, 414 Indigestion, 36, 38, 233, 241, 344, 373 Indomethacin, 91, 374 Induction, 30, 65, 70, 72, 89, 94, 95, 110, 115, 143, 148, 149, 154, 155, 161, 193, 235, 355, 374 Infarction, 101, 374 Infiltration, 29, 96, 112, 366, 374 Inflammatory bowel disease, 66, 190, 374 Information Systems, 87, 374 Infusion, 374, 411 Ingestion, 19, 49, 52, 122, 245, 258, 368, 374, 394 Inhalation, 374, 394 Initiation, 59, 88, 374, 388, 395, 401, 404, 411 Initiator, 147, 374 Inner ear, 374, 414 Inoculum, 102, 126, 374 Inorganic, 105, 367, 371, 374, 384, 386, 392 Inotropic, 357, 374 Insertional, 64, 164, 374 Insight, 81, 82, 95, 99, 112, 374 Insulin, 69, 375, 377 Insulin-dependent diabetes mellitus, 375 Integrins, 66, 375 Interferon, 112, 161, 167, 187, 189, 223, 273, 375 Interferon-alpha, 375 Interleukin-1, 167, 194, 220, 375 Interleukin-2, 375 Interleukin-8, 66, 131, 144, 148, 153, 161, 193, 205, 218, 236, 280, 375 Intermittent, 375, 379 Internal Capsule, 233, 375

Interstitial, 361, 375, 385 Intestinal Flora, 266, 376 Intestine, 266, 267, 343, 344, 359, 376, 377, 398, 407 Intoxication, 225, 376, 415 Intracellular Membranes, 354, 376, 381 Intravenous, 209, 374, 376 Intrinsic, 73, 145, 335, 342, 376 Invasive, 4, 12, 19, 22, 43, 49, 50, 59, 63, 79, 100, 114, 135, 201, 235, 255, 319, 372, 376 Involuntary, 342, 361, 376, 385, 400, 405 Ion Channels, 340, 376, 386 Ionization, 376 Ionizing, 245, 246, 336, 359, 376, 398, 399 Ions, 86, 123, 342, 345, 356, 358, 371, 376, 394 Ipecac, 18, 358, 376 Irritable Bowel Syndrome, 105, 277, 376 Ischemia, 341, 376 Isocitrate Lyase, 152, 376 J Jejunum, 233, 258, 376 Joint, 65, 340, 349, 363, 376, 388, 408 K Kb, 306, 376 Keratinocytes, 375, 376 Keratolytic, 355, 377 Ketone Bodies, 64, 333, 377 Kidney Disease, 306, 311, 316, 377 Kinetic, 105, 109, 120, 130, 138, 166, 376, 377 L Labile, 112, 350, 377 Large Intestine, 356, 376, 377, 400, 405 Laryngeal, 295, 377 Larynx, 377, 411 Latent, 377, 395 Laxative, 335, 358, 377 Least-Squares Analysis, 377, 400 Lectin, 88, 107, 135, 157, 377, 381 Leiomyoma, 362, 377, 405 Lens, 81, 339, 346, 377, 401 Lesion, 76, 100, 103, 112, 121, 238, 377, 379, 404, 412 Lethal, 232, 256, 341, 353, 377, 384 Leukemia, 310, 377 Leukocytes, 66, 78, 110, 344, 348, 360, 367, 374, 375, 377, 383, 391, 412 Leukotrienes, 37, 196, 340, 378 Levo, 356, 378 Levodopa, 356, 378 Library Services, 328, 378

426

Helicobacter pylori

Lichen Planus, 189, 378 Life cycle, 364, 378 Ligament, 378, 396 Ligands, 347, 375, 378 Ligase, 260, 261, 378 Ligase Chain Reaction, 260, 261, 378 Ligation, 124, 378 Likelihood Functions, 378, 400 Linear Models, 378, 400 Linkage, 187, 378, 391 Lipid, 68, 94, 106, 196, 225, 292, 339, 358, 375, 379, 389 Lipid Peroxidation, 379, 389 Lipopolysaccharide, 85, 94, 106, 144, 157, 165, 193, 196, 222, 367, 379 Lipoprotein, 122, 148, 179, 266, 367, 379 Lipoxygenase, 275, 340, 378, 379 Litter, 267, 379 Liver Cirrhosis, 17, 379 Liver Transplantation, 169, 379 Localization, 148, 163, 196, 373, 379 Localized, 86, 110, 355, 358, 362, 374, 378, 379, 393, 412 Locomotion, 362, 379, 393 Logistic Models, 379, 400 Long-Term Care, 98, 379 Loop, 370, 379 Low-density lipoprotein, 379 Lower Esophageal Sphincter, 365, 379 Luciferase, 81, 380 Lumen, 18, 117, 246, 359, 380 Lymph, 359, 371, 380 Lymphatic, 359, 374, 380, 405, 406, 410 Lymphocyte, 66, 121, 295, 338, 380, 381 Lymphoepithelioma, 207, 380 Lymphoid, 23, 89, 93, 117, 126, 140, 181, 191, 196, 338, 372, 380, 410 Lysosome, 380, 392 Lytic, 380, 404, 414 M Macrolides, 14, 125, 245, 259, 380 Macrophage, 90, 102, 144, 375, 380 Maintenance therapy, 62, 292, 380 Malabsorption, 310, 380 Malignancy, 61, 76, 87, 92, 93, 96, 241, 292, 319, 380 Malignant, 66, 93, 98, 177, 232, 256, 310, 334, 338, 380, 385, 399 Malignant tumor, 177, 380 Malnutrition, 8, 341, 380, 384 Manifest, 265, 380 Mannans, 364, 380

Matrix metalloproteinase, 189, 380 Maxillary, 177, 380, 381, 389 Maxillary Sinus, 177, 381 Meatus, 381 Mediate, 16, 44, 84, 104, 115, 117, 123, 124, 144, 154, 347, 357, 381, 399 Mediator, 66, 73, 188, 356, 375, 381, 393 Medical Records, 105, 381, 402 Medicament, 238, 244, 274, 381 MEDLINE, 4, 307, 309, 311, 381 Megaloblastic, 363, 381 Meiosis, 344, 381, 384, 408 Melanin, 381, 392, 412 Melanocytes, 381 Melanoma, 310, 381 Membrane Proteins, 72, 96, 132, 150, 263, 381, 397 Memory, 271, 338, 355, 381 Meninges, 347, 352, 381 Mental Disorders, 381, 395 Mental Health, iv, 62, 306, 308, 381, 395, 397 Mentors, 95, 99, 381 Mercury, 28, 36, 50, 51, 52, 56, 57, 60, 62, 363, 381 Mesolimbic, 271, 382 Metabolite, 344, 356, 382, 395 Metaphase, 344, 382 Metastasis, 347, 380, 382 Methionine, 356, 382, 408 Methylene Blue, 169, 382 MI, 154, 332, 382 Microbe, 93, 260, 382, 409, 410 Microbiological, 168, 260, 382 Microcirculation, 201, 379, 382, 393 Micronutrients, 217, 382 Microorganism, 49, 240, 244, 260, 350, 382, 390, 415 Micro-organism, 355, 357, 368, 382 Microscopy, 29, 75, 102, 117, 140, 145, 260, 342, 370, 382, 387 Microspheres, 153, 183, 382 Microwaves, 245, 383, 399 Migration, 66, 86, 137, 192, 272, 280, 383 Minocycline, 13, 383 Mitochondria, 109, 383, 388 Mitochondrial Swelling, 383, 385 Mitosis, 339, 383 Mobility, 236, 237, 383 Mode of Transmission, 18, 26, 50, 55, 286, 383 Modeling, 73, 75, 357, 383

Index 427

Modification, 106, 112, 141, 144, 148, 152, 154, 157, 164, 165, 365, 383, 398 Monitor, 44, 84, 93, 174, 181, 260, 383, 387 Monoamine, 271, 383 Monoclonal, 81, 108, 141, 147, 159, 165, 208, 268, 372, 383, 399 Monoclonal antibodies, 81, 159, 165, 268, 372, 383 Monocytes, 191, 220, 295, 375, 377, 383 Mononuclear, 26, 66, 101, 383, 412 Monotherapy, 58, 287, 383 Morphological, 127, 164, 228, 358, 364, 381, 383 Morphology, 29, 132, 143, 210, 279, 346, 383 Motility, 51, 117, 124, 131, 147, 152, 153, 163, 166, 228, 243, 258, 374, 384 Motion Sickness, 384, 385 Mucins, 18, 355, 384, 403 Mucociliary, 384, 405 Mucolytic, 333, 384 Mucus, 64, 100, 158, 209, 238, 242, 251, 264, 384, 413 Multicenter Studies, 24, 384 Multicenter study, 384 Multidrug resistance, 174, 270, 384 Multivalent, 112, 265, 384 Mupirocin, 222, 384 Muscidae, 371, 384 Muscle Fibers, 384 Muscular Atrophy, 310, 384 Muscular Dystrophies, 357, 384 Mustard Gas, 384 Mutagen, 75, 384 Mutagenesis, 64, 111, 120, 124, 125, 142, 148, 163, 164, 176, 384 Mutagenic, 76, 104, 152, 385 Mycobacterium, 121, 154, 270, 341, 385, 402, 412 Mydriatic, 356, 385 Myeloma, 371, 385 Myocardial infarction, 101, 342, 352, 382, 385 Myocardium, 382, 385 Myotonic Dystrophy, 310, 385 N Nasopharynx, 380, 385 Natural selection, 343, 385 Nausea, 8, 11, 23, 43, 56, 257, 268, 317, 319, 320, 344, 365, 373, 385, 386, 413 NCI, 1, 305, 349, 385 Necrosis, 86, 235, 339, 374, 382, 385

Neoplasia, 29, 93, 100, 273, 285, 310, 385 Neoplasm, 385 Neoplastic, 77, 112, 173, 187, 337, 380, 385 Nephritis, 108, 235, 385 Nephropathy, 108, 377, 385 Nerve, 334, 337, 340, 355, 381, 385, 394, 401, 403, 407, 412, 413 Nervous System, 310, 334, 347, 381, 385, 386, 391, 408 Networks, 96, 109, 385 Neural, 271, 334, 337, 371, 385 Neuronal, 278, 386 Neurons, 272, 355, 378, 386, 408 Neuropeptide, 252, 277, 386 Neurophysiology, 72, 355, 386 Neurotransmitters, 386 Neutrons, 335, 386, 398 Neutrophil, 16, 38, 66, 83, 154, 199, 386 Neutrophil Infiltration, 66, 386 Niche, 72, 83, 122, 143, 386 Nickel, 105, 122, 125, 133, 151, 154, 155, 386 Nitrates, 267, 386 Nitric acid, 386 Nitric Oxide, 89, 142, 167, 223, 274, 275, 276, 371, 386 Nitrogen, 89, 249, 280, 335, 336, 353, 361, 362, 366, 386 Nitrogenase, 106, 386 Nonulcer Dyspepsia, 33, 39, 51, 58, 62, 126, 128, 170, 198, 243, 281, 319, 386 Norepinephrine, 334, 357, 387 NSAIDs, 6, 16, 19, 23, 34, 35, 38, 58, 107, 274, 275, 286, 315, 387 Nuclear, 17, 115, 193, 222, 249, 321, 342, 358, 361, 364, 375, 385, 387 Nuclei, 335, 358, 365, 383, 386, 387, 397 Nucleic acid, 67, 132, 232, 239, 240, 250, 256, 365, 371, 373, 386, 387, 388, 398, 406 Nucleic Acid Hybridization, 371, 387 Nucleolus, 387, 402 Nursing Care, 387, 390 O Observational study, 219, 387 Occupational Exposure, 51, 387 Odds Ratio, 35, 65, 387, 400 Oesophagitis, 49, 175, 183, 196, 387 Ofloxacin, 13, 229, 387 Ointments, 387, 389 Olfaction, 387 Oligonucleotide Probes, 378, 388 Oligosaccharides, 149, 388

428

Helicobacter pylori

Oncogene, 180, 310, 388 Oncogenic, 375, 388 Opacity, 346, 355, 388 Operon, 64, 96, 147, 274, 388, 395, 401 Ophthalmic, 252, 388 Oral Hygiene, 368, 388 Organ Culture, 95, 388, 410 Organelles, 109, 117, 349, 354, 381, 383, 388, 393 Ori region, 388, 401 Ornithine, 89, 187, 388, 398 Ornithine Decarboxylase, 187, 388 Osteoarthritis, 275, 388 Outpatient, 26, 35, 388 Oxazolidinones, 222, 388 Oxidation, 333, 339, 344, 353, 366, 379, 389 Oxidative metabolism, 378, 389 Oxidative Stress, 72, 104, 110, 111, 155, 163, 389 Oxygen Consumption, 389, 401 P Paediatric, 321, 389 Palate, 385, 389, 410 Palliative, 389, 409 Pancreas, 333, 343, 356, 365, 369, 375, 389, 406 Pancreatic, 72, 87, 105, 310, 365, 389 Pancreatic cancer, 105, 310, 389 Pancreatic Juice, 365, 389 Pancreatitis, 105, 389 Paraffin, 107, 134, 212, 389 Paranasal Sinuses, 381, 389, 405 Parasite, 389, 412 Parasitic, 74, 107, 114, 353, 389 Parietal, 33, 66, 71, 81, 88, 112, 164, 276, 280, 389, 390, 391 Parietal Cells, 81, 88, 112, 164, 390 Parietal Lobe, 389, 390 Paroxysmal, 310, 368, 390 Partial remission, 390, 401 Particle, 390, 406, 411 Pathologic, 112, 230, 339, 343, 352, 371, 390, 414 Pathologic Processes, 339, 390 Pathologies, 37, 38, 90, 95, 390 Pathophysiology, 72, 252, 277, 282, 283, 285, 286, 390 Patient Care Management, 43, 390 Patient Compliance, 13, 41, 54, 80, 390 Patient Education, 316, 318, 319, 320, 326, 328, 332, 390 Patient Satisfaction, 15, 54, 62, 390

Patient Selection, 32, 37, 282, 290, 390 Pediatric Gastroenterologist, 194, 390 Peer Review, 78, 215, 390 Pelvic, 390, 396 Penicillin, 20, 125, 132, 147, 272, 336, 390 Pentosyltransferases, 367, 390 Pepsin, 233, 349, 390 Pepsin A, 349, 390 Peptide, 71, 72, 74, 97, 120, 213, 234, 272, 295, 348, 349, 390, 391, 394, 396, 397 Peptide Chain Elongation, 349, 391 Perception, 51, 351, 391, 403 Percutaneous, 245, 391 Perforated Ulcer, 47, 391 Perforation, 47, 286, 363, 391 Peripheral blood, 26, 96, 101, 255, 375, 391 Peripheral Nervous System, 391, 406, 408 Periplasm, 61, 391 Peritoneal, 246, 391 Peritoneal Cavity, 246, 391 Peritoneum, 391 Peroxidase, 104, 339, 340, 379, 391 Peroxide, 104, 391 Petroleum, 389, 391 PH, 117, 118, 167, 391 Phagocytosis, 102, 145, 280, 391 Phagosomes, 102, 391 Pharmaceutical Preparations, 229, 347, 361, 392 Pharmacokinetic, 392 Pharmacologic, 26, 337, 341, 392, 411 Pharynx, 241, 365, 385, 392, 410 Phenolsulfonphthalein, 232, 392 Phenotype, 25, 30, 75, 82, 83, 84, 100, 102, 108, 112, 115, 127, 138, 274, 392 Phenyl, 238, 255, 277, 392 Phenylalanine, 66, 390, 392, 412 Phorbol, 392, 397 Phorbol Esters, 392, 397 Phosphates, 68, 106, 392 Phospholipases, 392, 405 Phospholipids, 362, 379, 392, 397 Phosphorus, 345, 392 Phosphorylated, 350, 392 Phosphorylates, 392, 397 Phosphorylating, 103, 392 Phosphorylation, 30, 67, 103, 120, 128, 142, 147, 166, 172, 271, 392 Photocoagulation, 350, 392 Physiologic, 21, 66, 335, 343, 356, 382, 392, 396, 399

Index 429

Physiology, 36, 51, 63, 72, 83, 117, 120, 144, 152, 218, 284, 365, 386, 392 Pigment, 270, 348, 381, 393 Pilot study, 105, 113, 207, 216, 393 Plant Diseases, 359, 393 Plaque, 249, 292, 340, 393 Plasma, 82, 190, 260, 335, 338, 342, 347, 349, 354, 359, 362, 369, 385, 393, 400, 404 Plasma cells, 338, 385, 393 Plasmid, 76, 393, 414 Plasmin, 393 Plasminogen, 101, 393 Plasminogen Activators, 393 Plastids, 388, 393 Platelet Activation, 393, 405 Platelet Aggregation, 337, 386, 393, 409 Platelet Factor 4, 375, 393 Platelets, 67, 339, 342, 386, 393, 409, 410 Point Mutation, 134, 151, 159, 394 Poisoning, 269, 365, 376, 382, 385, 394, 403 Polycystic, 311, 394 Polymerase, 12, 50, 85, 128, 134, 159, 161, 166, 177, 250, 260, 261, 394, 395, 401, 404 Polymerase Chain Reaction, 12, 50, 128, 159, 161, 166, 260, 261, 394 Polymorphic, 85, 128, 129, 394 Polymorphism, 129, 132, 135, 147, 153, 156, 166, 187, 194, 199, 394 Polyp, 185, 394 Polyposis, 334, 394 Polysaccharide, 165, 220, 338, 347, 394 Population Control, 107, 394 Population Dynamics, 102, 394 Porins, 266, 394 Posterior, 337, 340, 375, 389, 394, 410 Postoperative, 15, 394 Postsynaptic, 394, 405 Potentiates, 375, 394 Potentiation, 394, 405 Practicability, 394, 412 Practice Guidelines, 54, 308, 320, 395 Precancerous, 4, 16, 78, 85, 348, 395 Precursor, 76, 81, 103, 112, 268, 340, 342, 356, 357, 360, 378, 387, 392, 393, 395, 406, 412 Predisposition, 107, 395 Premalignant, 69, 85, 100, 395 Prescription Fees, 357, 395 Presumptive, 129, 395 Prevalence, 4, 6, 8, 9, 24, 26, 31, 32, 44, 46, 47, 48, 51, 53, 60, 70, 85, 92, 98, 107, 115,

116, 124, 129, 141, 146, 157, 158, 185, 191, 204, 205, 237, 285, 296, 387, 395 Primary Prevention, 84, 101, 395 Probe, 67, 71, 105, 120, 124, 138, 378, 388, 395 Prodrug, 75, 395 Prognostic factor, 101, 395 Progression, 53, 70, 78, 88, 92, 97, 100, 107, 121, 216, 251, 337, 395 Progressive, 4, 21, 88, 100, 251, 347, 349, 355, 357, 367, 384, 385, 388, 393, 395 Projection, 354, 387, 395, 400 Proline, 74, 197, 350, 395 Promoter, 64, 81, 271, 395 Promotor, 395, 401 Prophase, 344, 384, 396, 408 Prophylaxis, 65, 236, 237, 244, 265, 396, 402, 413 Proportional, 360, 396 Prospective study, 10, 23, 43, 69, 219, 396 Prostaglandin, 6, 38, 65, 83, 93, 117, 121, 275, 396, 409 Prostaglandins A, 374, 396 Prostate, 69, 264, 265, 310, 396 Protease, 265, 350, 396 Protein C, 70, 80, 119, 126, 161, 292, 336, 339, 341, 350, 379, 396, 413 Protein Conformation, 336, 396 Protein Folding, 74, 396 Protein Kinase C, 66, 222, 397 Protein S, 119, 136, 143, 230, 272, 311, 344, 349, 358, 360, 365, 396, 397, 402, 409 Protein Subunits, 119, 397 Proteolytic, 251, 336, 351, 362, 393, 397 Protocol, 5, 11, 12, 27, 31, 48, 112, 122, 168, 397 Proton Pump Inhibitors, 4, 13, 27, 34, 40, 44, 47, 56, 61, 105, 198, 229, 237, 274, 275, 276, 278, 397 Protons, 335, 371, 376, 397, 398 Protozoa, 382, 397, 406 Proximal, 53, 60, 68, 356, 397 Pruritic, 378, 397 Psychic, 397, 403 Psychogenic, 233, 397 Public Health, 77, 85, 114, 144, 216, 219, 238, 308, 397 Public Policy, 307, 397 Publishing, 6, 35, 37, 38, 43, 44, 52, 54, 58, 59, 123, 287, 397 Pulmonary, 101, 344, 348, 351, 352, 378, 398, 414

430

Helicobacter pylori

Pulmonary Artery, 344, 398, 414 Pulmonary Edema, 348, 398 Pulmonary hypertension, 352, 398 Pulse, 383, 398 Pupil, 352, 356, 385, 398 Purifying, 64, 398 Purines, 398, 404 Purpura, 38, 180, 199, 398 Purulent, 398, 413 Putrescine, 388, 398, 406 Pylorus, 234, 398 Pyridoxal, 388, 398 Q Quality of Life, 10, 55, 398 Quaternary, 396, 397, 398 Quinolones, 51, 222, 398 R Race, 356, 383, 398 Radiation, 115, 245, 246, 358, 359, 363, 364, 376, 382, 398, 399, 408, 415 Radiation Chimera, 115, 398 Radiation therapy, 363, 398 Radio Waves, 245, 355, 383, 399 Radioactive, 57, 63, 71, 371, 376, 383, 387, 388, 398, 399 Radioimmunotherapy, 399 Radiolabeled, 52, 344, 399 Radiological, 391, 399 Radiology, 286, 399 Radiotherapy, 265, 399 Ranitidine, 7, 15, 25, 31, 41, 45, 55, 169, 200, 218, 219, 221, 223, 229, 399 Ranitidine Bismuth Citrate, 7, 15, 25, 31, 41, 45, 55, 169, 218, 223, 399 Reactive Oxygen Species, 73, 103, 110, 399 Reagent, 232, 235, 348, 371, 380, 399 Recombinant, 30, 74, 82, 108, 112, 113, 118, 120, 148, 151, 159, 175, 230, 234, 239, 250, 254, 262, 399, 414 Recombinant Proteins, 175, 399 Recombination, 75, 103, 152, 159, 271, 399 Reconstitution, 86, 399 Rectum, 265, 339, 344, 350, 354, 356, 361, 363, 364, 373, 374, 377, 396, 400 Recur, 279, 400 Red blood cells, 360, 369, 400 Red Nucleus, 340, 400 Reductase, 104, 105, 106, 153, 400, 409 Refer, 1, 252, 350, 362, 364, 370, 379, 386, 399, 400 Reflex, 234, 278, 400 Refraction, 338, 400, 406

Refractory, 20, 206, 287, 358, 400 Regeneration, 81, 399, 400 Regression Analysis, 23, 400 Regulon, 112, 141, 400 Regurgitation, 365, 368, 400 Relapse, 34, 181, 195, 229, 400 Relative risk, 61, 400 Reliability, 19, 160, 400 Remission, 292, 380, 400, 401 Replication Origin, 147, 401 Repressor, 150, 388, 401 Research Design, 112, 401 Resection, 15, 401 Resolving, 170, 401 Respiration, 150, 269, 345, 348, 383, 389, 401 Respiratory Burst, 67, 401 Respiratory Mucosa, 107, 401 Response Elements, 81, 401 Restitution, 86, 401 Restoration, 399, 401, 415 Retching, 268, 401 Retina, 377, 401, 402 Retinal, 351, 401 Retinoblastoma, 310, 402 Retreatment, 31, 402 Retrospective, 24, 169, 178, 402 Retrospective study, 169, 402 Retrosternal, 56, 402 Reversion, 111, 402, 412 Rheumatism, 372, 402 Rheumatoid, 4, 275, 277, 402 Rheumatoid arthritis, 4, 275, 277, 402 Rheumatology, 35, 402 Riboflavin, 145, 220, 402 Ribose, 334, 402 Ribosome, 81, 279, 402, 411 Rifabutin, 15, 160, 402 Rigidity, 393, 402 Risk patient, 6, 65, 402 Ristocetin, 402, 414 Rod, 236, 237, 243, 279, 341, 342, 349, 402, 403 Rural Population, 207, 402 S Salicylate, 241, 402 Saliva, 18, 27, 138, 259, 403 Salivary, 135, 154, 156, 267, 354, 355, 356, 389, 403 Salivary glands, 354, 355, 356, 403 Salmonella, 30, 74, 104, 112, 127, 234, 250, 262, 266, 269, 365, 403

Index 431

Sanitation, 286, 403 Schizoid, 403, 415 Schizophrenia, 277, 403, 415 Schizotypal Personality Disorder, 403, 415 Sclerosis, 310, 403 Screening, 6, 26, 32, 62, 82, 87, 109, 206, 235, 242, 247, 249, 262, 271, 273, 274, 316, 350, 403 Sebaceous, 403, 415 Secretory, 91, 151, 228, 267, 271, 276, 277, 278, 319, 403 Segregation, 399, 403 Seizures, 390, 403 Selection Bias, 65, 403 Selenium, 69, 220, 403 Self Care, 333, 403 Semen, 396, 403 Semisynthetic, 336, 349, 383, 404 Senile, 278, 404 Sensitization, 74, 404 Sensor, 69, 73, 144, 256, 404 Sepsis, 68, 106, 404 Sequence Analysis, 130, 136, 147, 153, 161, 404 Sequencing, 118, 132, 147, 158, 162, 368, 394, 404 Serine, 103, 197, 333, 397, 404 Serologic, 43, 57, 59, 101, 139, 143, 162, 191, 207, 372, 404 Serologic Tests, 59, 404 Serology, 10, 18, 19, 25, 26, 33, 42, 50, 57, 63, 138, 157, 162, 206, 213, 262, 404 Serous, 359, 404 Serum, 9, 34, 48, 57, 69, 76, 92, 97, 101, 102, 133, 144, 147, 159, 162, 166, 177, 180, 206, 230, 242, 255, 259, 260, 268, 269, 334, 336, 337, 350, 372, 379, 400, 404, 412 Sex Determination, 311, 404 Shedding, 18, 112, 404 Shock, 74, 92, 121, 124, 126, 134, 137, 143, 148, 163, 239, 262, 266, 404, 412 Sialyltransferases, 367, 404 Sigma Factor, 164, 404 Signal Transduction, 67, 72, 97, 117, 118, 120, 189, 404 Signs and Symptoms, 400, 401, 405, 413 Simethicone, 166, 405 Sinusitis, 177, 405 Skeletal, 349, 384, 405 Skeleton, 376, 396, 405 Small intestine, 243, 317, 343, 349, 357, 359, 364, 366, 370, 372, 376, 405

Smooth muscle, 252, 277, 337, 341, 345, 362, 370, 377, 405, 408 Smooth Muscle Tumor, 362, 405 Sneezing, 404, 405 Social Environment, 398, 405 Socioeconomic Factors, 51, 405 Sodium, 18, 127, 193, 405 Soft tissue, 344, 405 Solid tumor, 337, 405 Solvent, 333, 361, 405 Somatic, 347, 371, 381, 383, 391, 406 Somatic cells, 347, 381, 383, 406 Somatostatin, 117, 406 Sound wave, 351, 355, 406, 413 Spastic, 376, 406 Specialist, 62, 320, 323, 356, 406 Specificity, 10, 11, 18, 20, 32, 36, 37, 43, 44, 66, 67, 124, 128, 335, 340, 406 Spectrum, 17, 28, 74, 115, 249, 383, 399, 406 Sperm, 349, 406 Spermidine, 388, 406 Spinal cord, 340, 347, 348, 381, 385, 391, 400, 406 Spleen, 354, 371, 380, 406 Sporadic, 402, 406 Spores, 374, 406 Squamous, 186, 406 Standardize, 34, 80, 406 Staphylococcus, 74, 266, 365, 383, 406 Stasis, 47, 407 Statistically significant, 7, 14, 31, 35, 45, 62, 407 Steel, 349, 407 Stem Cells, 335, 407 Sterile, 110, 340, 407 Sternum, 402, 407 Steroids, 275, 407 Stimulant, 271, 370, 407 Stimulus, 67, 117, 244, 271, 361, 375, 376, 400, 407, 409 Stomach Ulcer, 27, 243, 319, 407 Stool test, 33, 407 Strand, 175, 394, 407 Streptococci, 384, 407 Stroke, 101, 292, 294, 306, 346, 407 Stromal, 29, 407 Subacute, 374, 405, 407 Subarachnoid, 368, 407 Subclinical, 77, 101, 161, 374, 403, 407 Subspecies, 406, 407

432

Helicobacter pylori

Substance P, 252, 277, 360, 382, 399, 402, 403, 408 Substrate, 52, 241, 275, 276, 360, 408 Sucralfate, 216, 408 Suction, 234, 408 Sulfur, 249, 277, 278, 361, 382, 408 Sunburn, 277, 278, 408 Superoxide, 106, 158, 163, 208, 401, 408 Superoxide Dismutase, 106, 158, 163, 408 Suppression, 30, 39, 241, 278, 408 Suppressive, 28, 49, 53, 60, 105, 251, 287, 408 Symbiosis, 68, 408 Sympathomimetic, 357, 360, 387, 408 Symphysis, 396, 408 Symptomatic, 6, 10, 39, 114, 169, 219, 389, 408 Symptomatology, 41, 408 Synaptic, 405, 408 Synergistic, 65, 120, 222, 229, 408 Systemic, 22, 38, 74, 95, 113, 208, 250, 300, 339, 344, 360, 374, 398, 408, 411, 412 Systolic, 371, 408 T Tachykinins, 252, 277, 408 Telangiectasia, 311, 409 Testosterone, 400, 409 Tetracycline Resistance, 52, 123, 137, 177, 409 Thalamic, 340, 409 Thalamic Diseases, 340, 409 Thermal, 122, 338, 356, 386, 394, 409 Thioredoxin, 104, 138, 409 Threonine, 397, 404, 409 Threshold, 19, 53, 93, 123, 371, 409 Thrombin, 362, 393, 396, 409 Thrombocytes, 393, 409 Thrombolytic, 393, 409 Thrombomodulin, 396, 409 Thrombosis, 342, 375, 397, 407, 409 Thromboxanes, 340, 409 Thrombus, 352, 374, 393, 409, 410 Thylakoids, 348, 410 Thymus, 372, 380, 410 Thyroid, 410, 412 Thyroid Gland, 410 Thyroiditis, 38, 410 Thyroxine, 392, 410 Time Factors, 335, 410 Tinidazole, 31, 229, 410 Tissue Culture, 90, 410 Titre, 268, 410

Tolerance, 45, 137, 333, 410 Tonsil, 176, 410 Tooth Preparation, 334, 410 Topical, 22, 287, 361, 371, 389, 410 Torsion, 374, 410 Toxic, iv, 70, 104, 119, 235, 236, 244, 267, 341, 353, 354, 359, 367, 372, 386, 398, 403, 410, 411, 414 Toxicity, 6, 34, 65, 201, 251, 275, 276, 357, 358, 382, 402, 408, 410 Toxicokinetics, 411 Toxicology, 116, 308, 411 Toxins, 82, 338, 344, 366, 374, 383, 399, 411, 414 Toxoplasmosis, 341, 411 Trace element, 106, 386, 411 Trachea, 345, 377, 392, 410, 411 Traction, 349, 411 Training Support, 98, 411 Transcriptase, 96, 127, 411 Transcription Factors, 74, 110, 118, 401, 411 Transduction, 97, 118, 404, 411 Transfection, 81, 343, 411 Transfer Factor, 372, 411 Transferases, 367, 411 Transfusion, 67, 121, 411 Translating, 92, 411 Translation, 71, 360, 411 Translational, 112, 411 Translocate, 112, 411 Translocation, 166, 349, 360, 411 Transmitter, 333, 340, 357, 376, 381, 387, 412 Transplantation, 169, 349, 372, 398, 412 Trauma, 360, 385, 389, 412 Treatment Failure, 7, 58, 87, 182, 220, 287, 412 Treatment Outcome, 34, 128, 412 Triage, 286, 412 Trichomoniasis, 382, 412 Tricuspid Atresia, 352, 412 Trigger zone, 376, 412 Triple-Therapy, 181, 412 Tropism, 88, 139, 164, 412 Tuberculosis, 114, 121, 154, 270, 351, 412 Tuberous Sclerosis, 311, 412 Tumor Necrosis Factor, 183, 220, 412 TYPHI, 112, 262, 412 Typhimurium, 74, 104, 250, 269, 412 Typhoid fever, 412

Index 433

Tyrosine, 30, 67, 74, 128, 142, 147, 153, 166, 172, 271, 292, 357, 412 U Ulceration, 37, 44, 52, 60, 110, 122, 177, 240, 261, 262, 273, 275, 283, 391, 413 Ulcerative colitis, 277, 374, 413 Ulcerogenic, 91, 413 Ultrasound test, 101, 413 Unconscious, 337, 354, 372, 413 Uraemia, 389, 413 Uremia, 24, 413 Ureters, 413 Urethra, 396, 413 Urinary, 69, 211, 246, 252, 277, 349, 366, 373, 413 Urinary tract, 246, 413 Urine, 50, 115, 153, 344, 369, 373, 377, 402, 413 Uterus, 352, 362, 363, 377, 413 V Vaccination, 28, 72, 85, 89, 98, 100, 112, 127, 131, 151, 261, 413 Vacuole, 266, 413 Vagina, 413 Vaginitis, 23, 413 Vagotomy, 15, 210, 413 Vancomycin, 272, 414 Vascular, 37, 38, 55, 67, 359, 368, 374, 379, 382, 386, 393, 410, 414 Vascular endothelial growth factor, 67, 414 Vasculitis, 389, 414 Vasoactive, 37, 414 Vasoconstriction, 360, 414 Vasodilation, 278, 414 Vasodilator, 345, 357, 370, 414 Vector, 76, 133, 146, 167, 234, 262, 374, 411, 414 Vein, 337, 340, 376, 387, 414 Venoms, 354, 414

Venous, 269, 340, 342, 397, 412, 414 Venous blood, 269, 414 Ventricle, 341, 352, 372, 398, 408, 412, 414 Ventricular, 267, 352, 412, 414 Venules, 344, 345, 359, 382, 414 Veterinary Medicine, 307, 414 Vibrio, 70, 348, 414 Vibrio cholerae, 70, 348, 414 Viral, 67, 107, 114, 235, 276, 333, 388, 411, 414 Virulent, 65, 76, 78, 95, 115, 262, 294, 414 Virus, 101, 108, 135, 213, 260, 341, 347, 359, 365, 375, 388, 393, 401, 411, 414 Viscera, 278, 406, 415 Viscosity, 333, 415 Vivo, 21, 30, 70, 75, 80, 81, 83, 84, 88, 90, 92, 94, 96, 99, 103, 112, 113, 115, 117, 120, 123, 133, 139, 149, 158, 164, 197, 198, 219, 232, 240, 242, 272, 273, 274, 287, 347, 369, 373, 409, 415 Vulgaris, 265, 415 W Weight Gain, 53, 267, 361, 415 White blood cell, 338, 342, 373, 377, 380, 384, 385, 386, 393, 415 Windpipe, 392, 410, 415 Withdrawal, 70, 415 World Health, 73, 92, 103, 117, 331, 415 World Health Organization, 73, 92, 103, 117, 331, 415 Wound Healing, 275, 347, 375, 380, 384, 415 X Xenograft, 141, 337, 415 X-ray, 245, 346, 363, 364, 384, 387, 398, 399, 415 Y Yeasts, 279, 364, 376, 392, 415 Z Zymogen, 396, 415

434

Helicobacter pylori

Index 435

436

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